Rh-Catalyzed diastereoselective desymmetrization of enone tethered-cyclohexadienones via tandem arylative cyclization

Sandip B. Jadhav§ ab, Satish B. Thopate§ ab, Jagadeesh Babu Nanubolu ab and Rambabu Chegondi *ab
aDepartment of Organic Synthesis & Process Chemistry, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad 500007, India. E-mail: rchegondi@iict.res.in; cramhcu@gmail.com
bAcademy of Scientific and Innovative Research (AcSIR), New Delhi 110025, India

Received 15th September 2018 , Accepted 4th October 2018

First published on 5th October 2018


The rhodium-catalyzed arylative cyclization of enone tethered-cyclohexadienones has been developed with high efficiency, thus providing cis-fused bicyclic enones in good yields and with excellent diastereoselectivities. Furthermore, this mild transformation has a broad range of substrate scope and excellent functional group tolerance. In addition, bicyclic products have an enone functionality, which can be a synthetically valuable handle for further transformations.


Introduction

Multiple C–C bond formation through single transformation for the synthesis of bioactive complex molecules has high demand in modern organic chemistry.1 In particular, diastereoselective tandem reactions have significant importance in the natural products and small molecule syntheses in terms of minimization of synthetic steps and increasing overall yields. Hence, a number of enantio- and diastereoselective tandem processes have been developed. Recently, the catalytic desymmetrization of cyclohexadienones, which are readily available from oxidative dearomatization of corresponding phenols, has been found as one of the most powerful tools in complex natural product synthesis.2 In recent elegant reports, many research groups demonstrated the use of transition-metal catalysis in the desymmetrization of cyclohexadienones to construct stereoselective complex frameworks.3–6 In 2013, Tian/Lin research groups reported the rhodium-catalyzed enantioselective desymmetrization of 1,6-dienynes via arylative cyclization.5b Later, the same research group demonstrated the arylative cyclization of alkyne-tethered cyclohexadienones by Rh(III)-catalyzed C–H activation with dual reactivity based on the nature of O-substituents at N-hydroxybenzamides.5d Recently, Lautens and co-workers established the desymmetrization of cyclohexa-2,5-dienols using rhodium-catalyzed redoxisomerization.5e Our research group very recently demonstrated the use of asymmetric hydrogenation in the desymmetrization of alkyne-tethered cyclohexadienones to afford cis-hydrobenzofurans and cis-hydroindoles in high yields with excellent enantioselectivity.7

As part of our program aimed at the desymmetrization of C2-symmetric molecules8 and enthused by recent advances in the area of rhodium catalyzed tandem Michael additions,9 we envisaged that the Rh-catalyzed arylative diastereoselective desymmetrization of prochiral cyclohexadienone-containing bis-enones via tandem double conjugate addition would be a novel approach to provide factionalized bicyclic products with a high level of diastereoselectivity. To the best of our knowledge, desymmetrization enone tethered-cyclohexadienones have not been explored until now.

Results and discussion

We initiated our studies with the arylation of cyclohexadienone 1a with phenylboronic acid 2a in the presence of 2.5 mol% of [Rh(COD)Cl]2 and 5 mol% of common phosphine ligands in 1,4-dioxane using various bases and results are summarized in Table 1. To our delight, the reaction at 90 °C with various bases (1 equiv.) gave desired cyclization product 3a along with an appreciable amount of uncycled product 4a, albeit with a low diastereoselectivity (Table 1, entries 1–3). Additional optimization revealed that the loading of the K2CO3 base from 1 equivalent to 2 equivalents at 90 °C (entries 4 & 5) led to further increases in the yield of 3a (86%) and diastereoselectivity (14[thin space (1/6-em)]:[thin space (1/6-em)]1). Next, various mono- and bisphosphine ligands (L2–L9) were screened to further improve the yield and diastereoselectivity. However, none of the tested ligands improved the reaction outcome (entries 6–13). Interestingly, the reaction at room temperature in the presence of the L1 ligand and KOtBu base afforded required product 3a in excellent yield (91%) and diastereoselectivity (dr 21[thin space (1/6-em)]:[thin space (1/6-em)]1). On the other hand, the use of K2CO3 at room temperature furnished the cyclization product 3a in lower yield along with major uncycled product 4a (entries 14–15). Finally, decreasing the base loading to below 1 equivalent gave no better results and the reaction without a base at room temperature furnished exclusively the uncycled product 4a in 89% yield (Table 1, entries 16–18). This clearly indicates that the Rh-enolate trapping via Michael addition is slower than the protonation of enolate. From the above screening results, two equivalents of the KOtBu base in the presence of the BINAP ligand (L1) at room temperature were the best condition for the tandem cyclization (Table 1, entry 15).
Table 1 Optimization of reaction conditionsa

image file: c8ob02284d-u1.tif

Entry [Rh]-Catalyst Ligand (mol%) Base (equiv.) T °C 3a + 4a dr (3a)c
Yieldb [%]
a The reaction was carried out with 1a (0.1 mmol), 2a (0.2 mmol), [Rh(COD)Cl]2 (2.5 mol%), ligand (5 mol%), H2O (0.5 mmol) in dioxane (1 mL) under a N2 atmosphere at room temperature. b Yield of the isolated products 3a and 4a. c Diastereomeric ratio (dr) was determined by 1H NMR analysis of the crude reaction mixture.
1 [Rh(COD)Cl]2 (rac)-BINAP, L1 tBuOK (1.0) 90 60 + 29 2[thin space (1/6-em)]:[thin space (1/6-em)]1
2 [Rh(COD)Cl]2 (rac)-BINAP, L1 K2CO3 (1.0) 90 72 + 21 5[thin space (1/6-em)]:[thin space (1/6-em)]2
3 [Rh(COD)Cl]2 (rac)-BINAP, L1 Cs2CO3 (1.0) 90 36 + 32 2[thin space (1/6-em)]:[thin space (1/6-em)]1
4 [Rh(COD)Cl]2 (rac)-BINAP, L1 K2CO3 (1.5) 90 84 + 5 9[thin space (1/6-em)]:[thin space (1/6-em)]1
5 [Rh(COD)Cl]2 (rac)-BINAP, L1 K2CO3 (2.0) 90 86 + 5 14[thin space (1/6-em)]:[thin space (1/6-em)]1
6 [Rh(COD)Cl]2 DPPF, L2 K2CO3 (2.0) 90 40 + 38 17[thin space (1/6-em)]:[thin space (1/6-em)]1
7 [Rh(COD)Cl]2 DPPE, L3 K2CO3 (2.0) 90 30 + 40 7[thin space (1/6-em)]:[thin space (1/6-em)]1
8 [Rh(COD)Cl]2 DPPP, L4 K2CO3 (2.0) 90 65 + 12 18[thin space (1/6-em)]:[thin space (1/6-em)]1
9 [Rh(COD)Cl]2 SPhos, L5 K2CO3 (2.0) 90 68 + 10 11[thin space (1/6-em)]:[thin space (1/6-em)]1
10 [Rh(COD)Cl]2 RuPhos, L6 K2CO3 (2.0) 90 72 + 5 9[thin space (1/6-em)]:[thin space (1/6-em)]1
11 [Rh(COD)Cl]2 XPhos, L7 K2CO3 (2.0) 90 65 + 12 12[thin space (1/6-em)]:[thin space (1/6-em)]1
12 [Rh(COD)Cl]2 PCy3, L8 K2CO3 (2.0) 90 80 + 7 12[thin space (1/6-em)]:[thin space (1/6-em)]1
13 [Rh(COD)Cl]2 HPCy3·BF4, L9 K2CO3 (2.0) 90 32 + 42 6[thin space (1/6-em)]:[thin space (1/6-em)]1
14 [Rh(COD)Cl]2 (rac)-BINAP, L1 K2CO3 (2.0) rt 12 + 55
15 [Rh(COD)Cl] 2 (rac)-BINAP, L1 tBuOK (2.0) rt 91 + 3 21[thin space (1/6-em)]:[thin space (1/6-em)]1
16 [Rh(COD)Cl]2 (rac)-BINAP, L1 tBuOK (0.1) rt 12 + 73
17 [Rh(COD)Cl]2 (rac)-BINAP, L1 tBuOK (0.3) rt 23 + 65
18 [Rh(COD)Cl]2 (rac)-BINAP, L1 rt 0 + 89


With the optimal reaction conditions in hand, the scope of bicyclic product formation was demonstrated with a variety of substituted boronic acids. As shown in Table 2, all para-substituted arylboronic acids, regardless of the electron-withdrawing or electron-donating character of the substituent at the phenyl ring, furnished products with good to excellent yields and diastereoselectivities (Table 2, 3a–3i). However, strong activating and deactivating substituents at the para-position gave slightly lower diastereoselectivity (3e, 3f & 3i). When the 3-halo substituted boronic acids were examined, the corresponding products (3j–3m) were all obtained in moderate yields. Other substituents in the meta-position gave desired products (3n–3p) in good yields and with good distereoselectivities. The reaction with ortho-substituted boronic acid gave corresponding product 3q in moderate yield (59%) most likely due to steric hindrance and with an excellent diastereomeric ratio (21[thin space (1/6-em)]:[thin space (1/6-em)]1). As for the 2-naphthylboronic acid and other heteroaromatic boronic acid, the reaction progressed, thus providing the corresponding bicyclic products (3r–3t) with good yields and diastereoselectivities. Single-crystal X-ray analysis of compound 3t unambiguously established its relative stereochemistry of the bicyclic framework (Fig. 1).10


image file: c8ob02284d-f1.tif
Fig. 1 ORTEP diagram of compound 3t at the 30% probability level.
Table 2 Substrate scope for boronic acidsa,b,c,d
a The reaction was carried out with 1a (0.1 mmol), 2 (0.2 mmol), [Rh(COD)Cl]2 (2.5 mol%), ligand (5 mol%), and H2O (0.5 mmol) in dioxane (1 mL) under a N2 atmosphere at room temperature. b Yield of the isolated products 3. c Diastereomeric ratio (dr) was determined by 1H NMR analysis of crude reaction mixture. d Minor isomers of 3e & 3f (3e′ & 3f′, respectively) were isolated and data were included in the Experimental section.
image file: c8ob02284d-u2.tif


As shown in Table 3, a range of enone tethered-cyclohexadienones underwent arylative cyclization smoothly under the standard conditions to afford bicyclic products with good to excellent diastereoselectivity. Substrates containing aryl ketones substituted with electron-donating and electron-withdrawing groups furnished good yields and good diastereoselectivities (3u–3aa). It is also noted that the reaction with 4-phenyl substituted aryl ketone gave corresponding product 3x with excellent yield (92%; dr = 24[thin space (1/6-em)]:[thin space (1/6-em)]1). Although there were various R substituents (Et, iPr and C2H4OTBS) at the quaternary carbon center, the tandem reaction proceeded well with good yields (Table 3; entries 3ab–3ad).

Table 3 Substrate scope for cyclohexadienonesa,b,c
a The reaction was carried out with 1 (0.1 mmol), 2a (0.2 mmol), [Rh(COD)Cl]2 (2.5 mol%), ligand (5 mol%), and H2O (0.5 mmol) in dioxane (1 mL) under a N2 atmosphere at room temperature. b Yield of the isolated products 3. c Diastereomeric ratio (dr) was determined by 1H NMR analysis of the crude reaction mixture.
image file: c8ob02284d-u3.tif


In addition, the tandem Michael addition of cyclohexadienone 5 bearing the ethylbromide group at the quaternary carbon center under standard reaction conditions with phenylboronic acid 2a afforded dehalogenated product 3ac in 74% yield with excellent diastereoselectivity (dr = 35[thin space (1/6-em)]:[thin space (1/6-em)]1) (Scheme 1). Interestingly, arylative cyclization of α,β-ester 6 did not participate to give corresponding cyclization product 7.


image file: c8ob02284d-s1.tif
Scheme 1 Other miscellaneous reactions.

The bicyclic product 1 has an enone functionality, which can be a synthetically valuable handle for further transformations. This was demonstrated with the treatment of 3ab with TBAF in dry THF which afforded the more complex tricyclic product 8 in 80% yield as a single diastereomer (Scheme 2).


image file: c8ob02284d-s2.tif
Scheme 2 Synthetic utility.

From the above experimental outcome and on the basis of previous Rh-catalyzed enone conjugate additions,9 we proposed the reaction pathway for the Rh-catalyzed arylative cyclization of cyclohexadienone-containing bis-enones in Scheme 3. The transmetalation of arylboronic acid to a more active hydroxorhodium(I) intermediate A furnished arylrhodium(I) intermediate B. The coordination of rhodium complex B to enone 1a followed by insertion into the aryl-rhodium bond gave intermediate C which is an equilibrium with rhodium enolate D as an oxa-π-allylrhodium complex. The hydrolysis of Rh-enolate D with H2O avoids the β-hydride elimination of intermediate C, followed by the base mediated cyclization to afford the required product and regenerates active hydroxorhodium(I) complex A.


image file: c8ob02284d-s3.tif
Scheme 3 Reaction pathway.

In summary, we have developed a rhodium-catalyzed diastereoselective desymmetrization of prochiral cyclohexadienones via a tandem conjugate addition reaction. The reaction proceeds via arylation of enone and subsequent hydrolysis of Rh-enolate followed by the base mediated cyclization. The use of water prevents the β-hydride elimination from the Rh-enolate intermediate. Further investigations on the applications of enone tethered-cyclohexadienones are in progress in our laboratory and will be reported in due course.

Experimental section

General information

Unless otherwise noted, all reagents were used as received from commercial suppliers. All reactions were performed under a nitrogen atmosphere and in a flame-dried or oven-dried glassware with magnetic stirring. All solvents were dried before use following the standard procedures. Reactions were monitored using thin-layer chromatography (SiO2). TLC plates were visualized with UV light (254 nm), iodine treatment or using p-anisaldehyde stain and β-naphthol stain. Column chromatography was carried out using silica gel (100–200 mesh) packed in glass columns. NMR spectra were recorded at 300, 400, and 500 MHz (H) and at 75, 100, and 125 MHz (C), respectively. Chemical shifts (δ) are reported in ppm, using the residual solvent peak in CDCl3 (H: δ = 7.26 and C: δ = 77.16 ppm) as the internal standard, and coupling constants (J) are given in Hz. HRMS spectra were recorded using ESI-TOF techniques.

General procedure for the rhodium-catalyzed diastereoselective arylative cyclization of enone-tethered cyclohexadienones

To a stirred solution of boronic acid 2 (2 equiv.) in dioxane (0.1 M) at room temperature were added [Rh(COD)Cl]2 (2.5 mol%) and (rac)-BINAP (5 mol%) under an inert atmosphere. After 5 minutes, KOtBu (2 equiv.), H2O (5 equiv.) and enone-tethered cyclohexadienone 1 (1 equiv.) were added to the reaction mixture, successively. The reaction mixture was allowed to stir at room temperature, until complete consumption of the starting material (monitored by TLC), at which point the reaction solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel (EtOAc in hexane) to give the desired product 3 along with its minor isomer 4.
4-Benzoyl-8a-methyl-3-phenyl-3,4,4a,8a-tetrahydro-2H-chromen-6(5H)-one (3a). Prepared according to the general procedure as described above in 91% yield (71 mg). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.4) to afford a brown semi solid; 1H NMR (400 MHz, CDCl3) δ 7.89–7.82 (m, 2H), 7.59–7.52 (m, 1H), 7.48–7.41 (m, 2H), 7.32–7.23 (m, 4H), 7.20–7.14 (m, 1H), 6.66 (d, J = 10.0 Hz, 1H), 6.00 (dd, J = 10.0, 0.8 Hz, 1H), 4.54 (dd, J = 11.7, 4.4 Hz, 1H), 3.95 (dd, J = 12.1, 5.7 Hz, 1H), 3.83 (t, J = 12.0 Hz, 1H), 3.66 (td, J = 11.8, 5.6 Hz, 1H), 2.89 (dd, J = 16.4, 13.7 Hz, 1H), 2.48 (dt, J = 13.6, 4.2 Hz, 1H), 1.98 (ddd, J = 16.4, 4.0, 0.8 Hz, 1H), 1.81 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.9, 198.1, 150.5, 139.5, 135.8, 133.7, 129.1, 128.8, 128.2, 128.0, 127.3, 69.9, 66.4, 46.3, 38.7, 37.6, 35.3, 22.4; HRMS (ESI) calcd for C23H23O3 [M + H]+: 347.1647; found: 347.1649.
4-Methyl-4-(4-oxo-2,4-diphenylbutoxy)cyclohexa-2,5-dienone (4a). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.5) to afford a brown semi solid; 1H NMR (400 MHz, CDCl3) δ 7.97–7.92 (m, 2H), 7.58–7.53 (m, 1H), 7.48–7.42 (m, 2H), 7.33–7.26 (m, 2H), 7.26–7.18 (m, 3H), 6.62 (ddd, J = 10.1, 2.4, 1.5 Hz, 1H), 6.55 (ddd, J = 10.4, 2.4, 1.5 Hz, 1H), 6.24–6.16 (m, 2H), 3.65–3.58 (m, 1H), 3.53–3.44 (m, 3H), 3.24 (dd, J = 16.6, 6.5 Hz, 1H), 1.31 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 198.7, 185.2, 151.8, 151.8, 141.9, 137.19, 133.1, 130.1, 130.0, 128.6, 128.5, 128.1, 127.9, 126.9, 72.5, 69.4, 41.9, 41.4, 26.2; HRMS (ESI) calcd for C23H22O3Na [M + Na]+: 369.1467; found: 369.1471.
4-Benzoyl-3-(4-chlorophenyl)-8a-methyl-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3b). Prepared according to the general procedure as described above in 71% yield (40 mg). It was purified by flash chromatography (20% EtOAc/hexanes; Rf = 0.4) to afford a white solid; mp = 139–141 °C; 1H NMR (400 MHz, CDCl3) δ 7.85 (dt, J = 8.5, 1.6 Hz, 2H), 7.59–7.54 (m, 1H), 7.48–7.43 (m, 2H), 7.25–7.21 (m, 4H), 6.66 (d, J = 10.0 H z, 1H), 6.00 (dd, J = 10.0, 0.9 Hz, 1H), 4.46 (dd, J = 11.7, 4.4 Hz, 1H), 3.91 (dd, J = 12.1, 5.6 Hz, 1H), 3.79 (t, J = 12.0 Hz, 1H), 3.64 (td, J = 11.8, 5.6 Hz, 1H), 2.86 (dd, J = 16.3, 13.7 Hz, 1H), 2.49 (dt, J = 13.7, 4.2 Hz, 1H), 1.96 (ddd, J = 16.2, 4.02, 0.8 Hz, 1H), 1.80 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.8, 197.9, 150.4, 138.0, 135.6, 133.9, 133.0, 129.4, 129.2, 129.0, 128.2, 69.9, 66.1, 46.5, 38.7, 37.2, 35.2, 22.4; HRMS (ESI) calcd for C23H22O3Cl [M + H]+: 381.1257; found: 381.1256.
4-Benzoyl-8a-methyl-6-oxo-3,4,4a,5,6,8a-hexahydro-2H-chromen-3-yl)benzoate (3c). Prepared according to the general procedure as described above in 89% yield (83 mg). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.3) to afford an orange semi solid; 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 8.3 Hz, 2H), 7.87–7.82 (m, 2H), 7.56 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 7.7 Hz, 2H), 7.37 (d, J = 8.3 Hz, 2H), 6.66 (d, J = 10.0 Hz, 1H), 6.01 (dd, J = 10.0, 0.7 Hz, 1H), 4.54 (dd, J = 11.6, 4.4 Hz, 1H), 4.3 (q, J = 7.1 Hz, 2H), 3.94 (dd, J = 11.9, 5.5 Hz, 1H), 3.84 (t, J = 11.8 Hz, 1H), 3.73 (td, J = 11.6, 5.5 Hz, 1H), 2.87 (dd, J = 16.3, 13.7 Hz, 1H), 2.51 (dt, J = 13.7, 4.2 Hz, 1H), 1.94 ((ddd, J = 16.3, 4.1, 0.7 Hz, 1H), 1.82 (s, 3H) 1.3 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 198.7, 197.9, 166.3, 150.3, 144.8, 135.6, 133.9, 130.1, 129.6, 129.2, 128.2, 128.1, 70.0, 66.0, 61.0, 46.4, 38.6, 37.9, 35.2, 22.4, 14.4; HRMS (ESI) calcd for C26H27O5 [M + H]+: 419.1858; found: 419.1856.
3-(4-Acetylphenyl)-4-benzoyl-8a-methyl-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3d). Prepared according to the general procedure as described above in 83% yield (72 mg). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.4) to afford a white solid; mp = 240–242 °C; 1H NMR (500 MHz, CDCl3) δ 7.88–7.83 (m, 4H), 7.59–7.54 (m, 1H), 7.45 (dd, J = 10.7, 4.8 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 6.66 (d, J = 10.0 Hz, 1H), 6.01 (dd, J = 10.0, 0.6 Hz, 1H), 4.54 (dd, J = 11.6, 4.4 Hz, 1H), 3.94 (dd, J = 12.0, 5.5 Hz, 1H), 3.84 (t, J = 11.9 Hz, 1H), 3.73 (td, J = 11.7, 5.5 Hz, 1H), 2.87 (dd, J = 16.3, 13.7 Hz, 1H), 2.53 (s, 3H), 2.50 (dt, J = 13.7, 7.9 Hz, 1H), 1.97 (ddd, J = 16.3, 4.0, 0.7 Hz, 1H), 1.82 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 198.6, 197.9, 197.6, 150.3, 145.2, 136.2, 135.5, 133.9, 129.2, 128.9, 128.3, 128.2, 70.0, 65.9, 46.4, 38.6, 37.9, 35.2, 26.7, 22.4; HRMS (ESI) calcd for C25H25O4 [M + H]+: 389.1753; found: 389.1753.
4-Benzoyl-8a-methyl-3-(4-(trifluoromethyl)phenyl)-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3e). Prepared according to the general procedure as described above in 63% yield (59 mg). It was purified by flash chromatography (20% EtOAc/hexanes; Rf = 0.5) to afford an orange solid; mp = 165–167 °C; 1H NMR (400 MHz, CDCl3) δ 7.88–7.82 (m, 2H), 7.60–7.55 (m, 1H), 7.52 (d, J = 8.1 Hz, 2H), 7.45 (dd, J = 17.4, 8.1 Hz, 4H), 6.66 (d, J = 10.0 Hz, 1H), 6.01 (dd, J = 10.0,0.7 Hz, 1H), 4.52 (dd, J = 11.5, 4.4 Hz, 1H), 3.94 (dd, J = 11.8, 5.3 Hz, 1H), 3.82 (t, J = 9.4 Hz, 1H), 3.73 (td, J = 11.6, 5.3 Hz, 1H), 2.86 (dd, J = 16.3, 13.7 Hz, 1H), 2.52 (dt, J = 13.6, 4.2 Hz, 1H), 1.97 (ddd, J = 16.2, 4.0, 0.7 Hz, 1H), 1.82 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.6, 197.9, 150.3, 143.8, 135.5, 134.0, 132.2 (q, JCF = 8.7 Hz), 129.3, 129.2 (q, JCF = 32.6 Hz), 128.4, 128.2, 126.9 (q, JCF = 272.5 Hz), 125.8 (q, JCF = 3.4 Hz), 70.0, 66.0, 46.4, 38.7, 37.8, 35.2, 22.4; 19F NMR (CDCl3) δ −62.6 (s); HRMS (ESI) calcd for C24H22O3F3 [M + H]+: 415.1521; found: 415.1518.
Minor isomer of 3e (3e′). Prepared according to the general procedure as described above in 8% yield (7.4 mg). It was purified by flash chromatography (20% EtOAc/hexanes; Rf = 0.5) to afford a white solid; mp = 134–136 °C; 1H NMR (500 MHz, CDCl3) δ 7.77 (dd, J = 8.3, 1.2 Hz, 2H), 7.63–7.59 (m, 1H), 7.48 (dd, J = 10.7, 4.9 Hz, 2H), 7.43 (d, J = 8.1 Hz, 2H), 7.25 (dd, J = 6.4, 2.3 Hz, 2H), 6.89 (dd, J = 10.4, 2.2 Hz, 1H), 6.19 (dd, J = 10.4, 1.2 Hz, 1H), 4.17 (dd, J = 12.0, 3.0 Hz, 1H), 4.06 (dd, J = 12.0, 1.2 Hz, 1H), 4.02 (dd, J = 12.0, 5.4 Hz, 1H), 3.19–3.15 (m, 1H), 3.07–3.01 (m, 1H), 2.75 (dd, J = 17.8, 5.2 Hz, 1H), 2.33–2.28 (m, 1H), 1.72 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.2, 197.3, 154.8, 143.6, 136.8, 133.8, 131.2, 129.7, 129.2, 128.3, 127.0(q, JCF = 286.9 Hz), 125.1 (q, JCF = 3.4 Hz), 74.2, 67.3, 47.2, 42.5, 39.9, 36.9, 29.8, 26.8; 19F NMR (CDCl3) δ −62.6 (s); HRMS (ESI) calcd for C24H22O3F3 [M + H]+: 415.1521; found: 415.1514.
4-Benzoyl-8a-methyl-3-(4-nitrophenyl)-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3f). Prepared according to the general procedure as described above in 69% yield (60 mg). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.3) to afford a yellow solid; mp = 203–205 °C; 1H NMR (400 MHz, CDCl3) δ 8.15–8.10 (m, 2H), 7.84 (dt, J = 8.5, 1.6 Hz, 2H), 7.61–7.55 (m, 1H), 7.51–7.43 (m, 4H), 6.66 (d, J = 10.0 Hz, 1H), 6.01 (dd, J = 10.0, 0.8 Hz, 1H), 4.52 (dd, J = 11.2, 4.4 Hz, 1H), 3.95 (dd, J = 11.2, 4.8 Hz, 1H), 3.89–3.74 (m, 2H), 2.84 (dd, J = 16.3, 13.7 Hz, 1H), 2.55 (dt, J = 13.7, 4.2 Hz, 1H), 2.00–1.93 (ddd, J = 16.2, 4.08, 0.8 Hz, 1H), 1.83 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.3, 197.7, 150.1, 147.4, 147.2, 135.3, 134.1, 129.3, 129.0, 128.2, 124.1, 70.1, 65.7, 46.7, 38.6, 38.0, 35.1, 22.4; HRMS (ESI) calcd for C23H22O5N [M + H]+: 392.1498; found: 392.1494.
Minor isomer of 3f (3f′). Prepared according to the general procedure as described above in 9% yield (8 mg). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.3) to afford a pale yellow semi solid; 1H NMR (400 MHz, CDCl3) δ 8.07–8.02 (m, 2H), 7.80–7.76 (m, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.7 Hz, 2H), 7.31 (d, J = 8.8 Hz, 2H), 6.89 (dd, J = 10.4, 2.2 Hz, 1H), 6.20 (dd, J = 10.4, 1.0 Hz, 1H), 4.18 (dd, J = 12.2, 3.0 Hz, 1H), 4.07 (dd, J = 11.1, 0.9 Hz, 1H), 4.05 (dd, J = 12.1, 5.5 Hz, 1H), 3.25–3.19 (m, 1H), 3.02 (ddd, J = 9.9, 5.1, 2.5 Hz, 1H), 2.76 (dd, J = 17.8, 5.2 Hz, 1H), 2.27 (dt, J = 17.8, 1.5 Hz, 1H), 1.73 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.04, 197.05, 154.52, 147.25, 147.20, 136.59, 134.01, 131.25, 130.23, 129.33, 128.26, 123.36, 74.27, 66.87, 47.12, 42.49, 39.92, 36.95, 26.81; HRMS (ESI) calcd for C23H22NO5 [M + H]+: 392.1498; found: 392.1497.
4-Benzoyl-3-(4-(tert-butyl)phenyl)-8a-methyl-3,4,4a,8a-tetrahydro-2H-chromen-6(5H)-one (3g). Prepared according to the general procedure as described above in 85% yield (51 mg). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.4) to afford a white solid mp = 215–217 °C; 1H NMR (400 MHz, CDCl3) δ 7.91–7.84 (m, 2H), 7.60–7.53 (m, 1H), 7.49–7.42 (m, 2H), 7.29–7.25 (m, 2H), 7.23–7.19 (m, 2H), 6.66 (d, J = 10.0 Hz, 1H), 5.99 (dd, J = 10.0, 0.8 Hz, 1H), 4.52 (dd, J = 11.7, 4.4 Hz, 1H), 3.94 (dd, J = 12.1, 5.6 Hz, 1H), 3.81 (t, J = 12.0 Hz, 1H), 3.64 (td, J = 11.8, 5.6 Hz, 1H), 2.89 (dd, J = 16.4, 13.7 Hz, 1H), 2.47 (dt, J = 13.7, 4.2 Hz, 1H), 1.97 (ddd, J = 16.3, 4.0, 0.8 Hz, 1H), 1.80 (s, 3H) 1.24 (s, 9H); 13C NMR (126 MHz, CDCl3) δ 198.9, 198.1, 150.5, 149.8, 136.1, 135.8, 133.5, 129.0, 128.1, 127.5, 125.6, 69.8, 66.4, 46.2, 38.6, 36.9, 35.2, 34.4, 31.3, 22.3; HRMS (ESI) calcd for C27H30NaO3 [M + Na]+: 425.2093; found: 425.2095.
3-([1,1′-Biphenyl]-4-yl)-4-benzoyl-8a-methyl-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3h). Prepared according to the general procedure as described above in 79% yield (50 mg). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.5) to afford a white solid; mp = 216–218 °C; 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 7.7 Hz, 2H), 7.59–7.54 (m, 1H), 7.53–7.43 (m, 6H), 7.39 (ddd, J = 8.2, 6.6, 3.1 Hz, 4H), 7.33–7.28 (m, 1H), 6.68 (d, J = 10.0 Hz, 1H), 6.01 (d, J = 10.0 Hz, 1H), 4.57 (dd, J = 11.7, 4.4 Hz, 1H), 3.99 (dd, J = 12.0, 5.6 Hz, 1H), 3.87 (t, J = 12.0 Hz, 1H), 3.72 (td, J = 11.8, 5.6 Hz, 1H), 2.92 (dd, J = 16.3, 13.7 Hz, 1H), 2.51 (dt, J = 13.7, 4.2 Hz, 1H), 2.00 (dd, J = 16.3, 4.0 Hz, 1H), 1.83 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.9, 198.2, 150.5, 140.8, 140.2, 138.5, 135.8, 133.7, 129.2, 128.8, 128.4, 128.2, 127.6, 127.4, 127.1, 70.0, 66.4, 46.4, 38.7, 37.3, 35.3, 22.4; HRMS (ESI) calcd for C29H27O3 [M + H]+: 423.1960; found: 423.1942.
4-Benzoyl-8a-methyl-3-(4-(methylthio)phenyl)-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3i). Prepared according to the general procedure as described above in 79% yield (45 mg). It was purified by flash chromatography (20% EtOAc/hexanes; Rf = 0.4) to afford a pale brown solid; mp = 214–216 °C; 1H NMR (400 MHz, CDCl3) δ 7.87–7.83 (m, 2H), 7.59–7.54 (m, 1H), 7.48–7.42 (m, 2H), 7.24–7.20 (m, 2H), 7.17–7.13 (m, 2H), 6.66 (d, J = 10.0 Hz, 1H), 6.00 (dd, J = 10.0, 0.8 Hz, 1H), 4.48 (dd, J = 11.7, 4.4 Hz, 1H), 3.92 (dd, J = 12.1, 5.6 Hz, 1H), 3.80 (t, J = 12.0 Hz, 1H), 3.62 (td, J = 11.8, 5.6 Hz, 1H), 2.87 (dd, J = 16.4, 13.7 Hz, 1H), 2.84 (dt, J = 13.6, 4.2 Hz, 1H), 2.41 (s, 3H), 1.96 (ddd, J = 16.4, 4.0, 0.8 Hz, 1H), 1.80 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.9, 198.0, 150.5, 137.2, 136.4, 135.8, 133.8, 129.2, 128.5, 128.2, 127.1, 69.9, 66.3, 46.5, 38.7, 37.2, 35.2, 22.4, 16.0; HRMS (ESI) calcd for C24H25O3S [M + H]+: 393.1524; found: 393.1517.
(4-Benzoyl-3-(3-bromophenyl)-8a-methyl-3,4,4a,8a-tetrahydro-2H-chromen-6(5H)-one (3j). Prepared according to the general procedure as described above in 47% yield (30 mg). It was purified by flash chromatography (20% EtOAc/hexanes; Rf = 0.5) to afford a pale yellow semi solid; 1H NMR (500 MHz, CDCl3) δ 7.87–7.84 (m, 2H), 7.60–7.55 (m, 1H), 7.49–7.44 (m, 2H), 7.43 (t, J = 1.8 Hz, 1H), 7.33–7.30 (m, 1H), 7.26–7.22 (m, 1H), 7.14 (t, J = 7.8 Hz, 1H), 6.66 (d, J = 10.0 Hz, 1H), 6.00 (dd, J = 10.0, 0.8 Hz, 1H), 4.46 (dd, J = 11.8, 4.5 Hz, 1H), 3.92 (dd, J = 12.1, 5.6 Hz, 1H), 3.80 (t, J = 12.0 Hz, 1H), 3.63 (td, J = 11.8, 5.5 Hz, 1H), 2.84 (dd, J = 16.3, 13.7 Hz, 1H), 2.49 (dt, J = 13.7, 4.2 Hz, 1H), 1.96 (ddd, J = 16.4, 4.1, 0.8 Hz, 1H), 1.81 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 198.6, 197.7, 150.2, 141.9, 135.5, 133.8, 130.8, 130.4, 130.3, 129.1, 128.1, 126.9, 122.8, 69.8, 66.0, 46.3, 38.6, 37.4, 35.0, 22.3; HRMS (ESI) calcd for C23H22BrO3 [M + H]+: 425.0752; found: 425.0748.
4-Benzoyl-3-(3-chlorophenyl)-8a-methyl-3,4,4a,8a-tetrahydro-2H-chromen-6(5H)-one (3k). Prepared according to the general procedure as described above in 58% yield (49 mg). It was purified by flash chromatography (20% EtOAc/hexanes; Rf = 0.5) to afford a colourless oil; 1H NMR (500 MHz, CDCl3) δ 7.88–7.84 (m, 2H), 7.60–7.55 (m, 1H), 7.46 (dd, J = 10.7, 4.8 Hz, 2H), 7.28–7.26 (m, 1H), 7.22–7.12 (m, 3H), 6.66 (d, J = 10.0 Hz, 1H), 6.00 (dd, J = 10.0, 0.8 Hz, 1H), 4.47 (dd, J = 11.7, 4.5 Hz, 1H), 3.93 (dd, J = 12.1, 5.6 Hz, 1H), 3.81 (t, J = 12.0 Hz, 1H), 3.64 (td, J = 11.8, 5.6 Hz, 1H), 2.85 (dd, J = 16.3, 13.7 Hz, 1H), 2.49 (dt, J = 13.6, 4.2 Hz, 1H), 1.96 (ddd, J = 16.4, 4.0, 0.8 Hz, 1H), 1.81 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 198.6, 197.8, 150.2, 141.6, 135.5, 134.5, 133.8, 130.0, 129.1, 128.1, 127.9, 127.4, 126.4, 69.8, 66.0, 46.3, 38.6, 37.4, 35.1, 22.3; HRMS (ESI) calcd for C23H22ClO3 [M + H]+: 381.1257; found: 381.1255.
4-Benzoyl-3-(3-fluorophenyl)-8a-methyl-3,4,4a,8a-tetrahydro-2H-chromen-6(5H)-one (3l). Prepared according to the general procedure as described above in 55% yield (44 mg). It was purified by flash chromatography (20% EtOAc/hexanes; Rf = 0.5) to afford a white solid mp = 200–202 °C; 1H NMR (400 MHz, CDCl3) δ 7.88–7.84 (m, 2H), 7.60–7.55 (m, 1H), 7.49–7.43 (m, 2H), 7.23 (dt, J = 14.0, 4.0 Hz, 1H), 7.09 (d, J = 7.8 Hz, 1H), 7.02–6.97 (m, 1H), 6.87 (tdd, J = 8.5, 2.5, 0.9 Hz, 1H), 6.66 (d, J = 10.0 Hz, 1H), 6.00 (dd, J = 10.0, 0.8 Hz, 1H), 4.48 (dd, J = 11.7, 4.4 Hz, 1H), 3.94 (dd, J = 12.0, 5.5 Hz, 1H), 3.81 (t, J = 11.9 Hz, 1H), 3.67 (td, J = 11.7, 5.5 Hz, 1H), 2.86 (dd, J = 16.3, 13.7 Hz, 1H), 2.49 (dt, J = 13.7, 4.2 Hz, 1H), 2.00–1.94 (ddd, J = 16.3, 4.1, 0.8 Hz, 1H), 1.81 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.6, 197.8, 162.9 (d, JCF = 246.4 Hz), 150.2, 142.0 (d, JCF = 6.4 Hz), 135.5, 133.7, 130.2 (d, JCF = 8.4 Hz), 129.1, 128.1, 123.8 (d, JCF = 2.1 Hz), 114.7 (d, JCF = 21.5 Hz), 114.1 (d, JCF = 21.1 Hz), 69.9, 66.0, 46.3, 38.5, 37.4, 35.1, 22.29; 19F NMR (CDCl3) δ −112.6 (s); HRMS (ESI) calcd for C23H22FO3 [M + H]+: 365.1553; found: 365.1552.
4-Benzoyl-8a-methyl-6-oxo-3,4,4a,5,6,8a-hexahydro-2H-chromen-3-yl)-2-fluorobenzonitrile (3m). Prepared according to the general procedure as described above in 64% yield (56 mg). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.4) to afford a white solid; mp = 175–177 °C; 1H NMR (400 MHz, CDCl3) δ 7.87–7.82 (m, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.56–7.50 (m, 1H), 7.47 (t, J = 7.8 Hz, 2H), 7.23 (dd, J = 8.1, 1.5 Hz, 1H), 7.17 (dd, J = 9.8, 1.4 Hz, 1H), 6.65 (d, J = 10.0 Hz, 1H), 6.01 (d, J = 10.0 Hz, 1H), 4.43 (dd, J = 11.3, 4.4 Hz, 1H), 3.93 (dd, J = 11.6, 5.1 Hz, 1H), 3.80 (t, J = 11.6 Hz, 1H), 3.76–3.67 (m, 1H), 2.80 (dd, J = 16.2, 13.7 Hz, 1H), 2.54 (dt, J = 13.7, 4.2 Hz, 1H), 1.94 (dd, J = 16.2, 3.9 Hz, 1H), 1.81 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.2, 197.6, 163.3 (d, JCF = 259.6 Hz), 150.0, 148.6 (d, JCF = 7.3 Hz), 135.1, 134.2, 133.8, 129.4, 129.3, 128.2 (d, JCF = 2.8 Hz), 124.8, 116.2 (d, JCF = 19.6 Hz), 113.8, 100.3 (d, JCF = 15.4 Hz), 70.1, 65.5, 46.6, 38.6, 38.2, 35.0, 22.41; 19F NMR (CDCl3) δ −105.7 (s); HRMS (ESI) calcd for C24H21O3NF [M + H]+: 390.1505; found: 390.1502.
3-(3-Acetylphenyl)-4-benzoyl-8a-methyl-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3n). Prepared according to the general procedure as described above in 81% yield (72 mg). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.4) to afford a white solid; mp = 229–231 °C; 1H NMR (400 MHz, CDCl3) δ 7.91 (t, J = 1.7 Hz, 1H), 7.87–7.83 (m, 2H), 7.77–7.75 (m, 1H), 7.57–7.53 (m, 2H), 7.48–7.42 (m, 2H), 7.38 (dd, J = 9.6, 5.8 Hz, 1H), 6.67 (d, J = 10.0 Hz, 1H), 6.01 (dd, J = 10.0, 0.8 Hz, 1H), 4.55 (dd, J = 11.7, 4.4 Hz, 1H), 3.94 (dd, J = 12.0, 5.8 Hz, 1H), 3.86 (t, J = 11.9 Hz, 1H), 3.76–3.68 (m, 1H), 2.88 (dd, J = 16.3, 13.7 Hz, 1H), 2.56 (s, 3H), 2.51 (dt, J = 13.8, 4.4 Hz, 1H), 1.97 (ddd, J = 16.3, 4.0, 0.8 Hz, 1H), 1.83 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.6, 198.1, 198.0, 150.3, 140.2, 137.4, 135.5, 133.7, 133.6, 129.1, 129.1, 129.0, 128.1, 127.6, 126.7, 69.9, 66.0, 46.5, 38.6, 37.6, 35.1, 26.7, 22.4; HRMS (ESI) calcd for C25H24NaO4 [M + Na]+: 411.1572; found: 411.1574.
4-Benzoyl-3-(3-methoxyphenyl)-8a-methyl-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3o). Prepared according to the general procedure as described above in 73% yield (62 mg). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.5) to afford a pale yellow semi solid; 1H NMR (500 MHz, CDCl3) δ 7.86 (dd, J = 8.3, 1.1 Hz, 2H), 7.59–7.53 (m, 1H), 7.48–7.42 (m, 2H), 7.18 (t, J = 7.9 Hz, 1H), 6.88 (d, J = 7.7 Hz, 1H), 6.86–6.82 (m, 1H), 6.71 (ddd, J = 16.1, 6.4, 4.6 Hz, 1H), 6.66 (d, J = 10.0 Hz, 1H), 5.99 (dd, J = 10.0, 0.7 Hz, 1H), 4.52 (dd, J = 11.8, 4.4 Hz, 1H), 3.94 (dd, J = 12.1, 5.6 Hz, 1H), 3.80 (ddd, J = 9.3, 7.1, 6.4 Hz, 1H), 3.76 (s, 3H), 3.64 (td, J = 11.8, 5.6 Hz, 1H), 2.88 (dd, J = 16.4, 13.7 Hz, 1H), 2.47 (dt, J = 13.6, 4.2 Hz, 1H), 1.98 (ddd, J = 16.4, 4.0, 0.7 Hz, 1H), 1.80 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.9, 198.1, 159.8, 150.5, 141.2, 135.8, 133.7, 129.8, 129.2, 128.2, 120.3, 114.5, 112.0, 70.0, 66.5, 55.3, 46.3, 38.7, 37.7, 35.3, 22.4; HRMS (ESI) calcd for C24H25O4 [M + H]+: 377.1753; found: 377.1746.
4-Benzoyl-3-(3,5-dimethoxyphenyl)-8a-methyl-3,4,4a,8a-tetrahydro-2H-chromen-6(5H)-one (3p). Prepared according to the general procedure as described above in 74% yield (67 mg). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.4) to afford a pale yellow solid; mp = 197–199 °C; 1H NMR (400 MHz, CDCl3) δ 7.89–7.85 (m, 2H), 7.55 (dd, J = 10.5, 4.3 Hz, 1H), 7.49–7.42 (m, 2H), 6.65 (d, J = 10.0 Hz, 1H), 6.44 (d, J = 2.2 Hz, 2H), 6.27 (t, J = 2.2 Hz, 1H), 5.99 (dd, J = 10.0, 0.6 Hz, 1H), 4.50 (dd, J = 11.8, 4.4 Hz, 1H), 3.94 (dd, J = 12.1, 5.6 Hz, 1H), 3.83–3.75 (m, 1H), 3.73 (s, 6H), 3.64–3.54 (m, 1H), 2.86 (dd, J = 16.3, 13.7 Hz, 1H), 2.46 (dt, J = 13.6, 4.1 Hz, 1H), 1.97 (ddd, J = 16.3, 3.5, 0.7 Hz, 1H), 1.78 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 198.9, 198.1, 161.0, 150.5, 142.0, 135.8, 133.7, 129.2, 128.2, 106.5, 98.5, 70.0, 66.5, 55.4, 46.1, 38.6, 38.0, 35.3, 22.4; HRMS (ESI) calcd for C25H27O5 [M + H]+: 407.1858; found: 407.1855.
4-Benzoyl-3-(2-methoxyphenyl)-8a-methyl-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3q). Prepared according to the general procedure as described above in 59% yield (50 mg). It was purified by flash chromatography (20% EtOAc/hexanes; Rf = 0.4) to afford a white solid; mp = 159–161 °C; 1H NMR (500 MHz, CDCl3) δ 7.86 (dd, J = 8.3, 1.1 Hz, 2H), 7.55 (ddd, J = 8.6, 2.4, 1.2 Hz, 1H), 7.44 (dd, J = 10.6, 4.8 Hz, 2H), 7.19 (dd, J = 7.7, 1.5 Hz, 1H), 7.17–7.12 (m, 1H), 6.86–6.82 (m, 2H), 6.66 (d, J = 10.0 Hz, 1H), 5.98 (dd, J = 10.0, 0.7 Hz, 1H), 4.95 (d, J = 6.0 Hz, 1H), 3.98–3.90 (m, 3H), 3.89 (s, 3H), 2.94 (dd, J = 16.4, 13.7 Hz, 1H), 2.46 (dt, J = 13.6, 4.2 Hz, 1H), 1.97 (ddd, J = 16.4, 3.9, 0.7 Hz, 1H), 1.80 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 199.4, 198.7, 157.9, 150.8, 136.2, 133.5, 129.5, 129.1 (2C), 128.2 (2C), 127.1, 121.1, 111.3, 70.0, 64.1, 55.6, 44.0, 39.0, 35.2, 34.1, 22.4; HRMS (ESI) calcd for C24H25O4 [M + H]+: 377.1753; found: 377.1751.
4-Benzoyl-8a-methyl-3-(naphthalen-1-yl)-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3r). Prepared according to the general procedure as described above in 60% yield (35 mg). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.5) to afford a white solid; mp = 230–232 °C; 1H NMR (500 MHz, CDCl3) δ 8.45 (d, J = 8.6 Hz, 1H), 7.91 (d, J = 7.3 Hz, 2H), 7.83 (d, J = 8.1 Hz, 1H), 7.68 (dd, J = 7.2, 2.0 Hz, 1H), 7.63 (ddd, J = 8.4, 6.9, 1.2 Hz, 1H), 7.57 (t, J = 7.4 Hz, 1H), 7.51 (td, J = 7.2,0.7 Hz, 1H), 7.46 (t, J = 7.7 Hz, 2H), 7.34–7.29 (m, 2H), 6.70 (d, J = 10.0, 1H), 6.04 (dd, J = 10.0, 0.7 Hz, 1H), 4.87 (dd, J = 11.7, 4.4 Hz, 1H), 4.58 (td, J = 11.8, 5.2 Hz, 1H), 4.09 (dd, J = 12.3, 5.2 Hz, 1H), 3.81 (t, J = 12.1 Hz, 1H), 3.09 (dd, J = 16.3, 13.7 Hz, 1H), 2.62 (dt, J = 13.7, 4.2 Hz, 1H), 2.07 (ddd, J = 16.3, 4.0, 0.7 Hz, 1H), 1.86 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.9, 198.1, 150.5, 135.9, 135.8, 134.2, 133.8, 132.3, 129.2, 129.0, 128.3, 127.8, 126.7, 126.1, 125.2, 123.2, 122.5, 70.2, 66.4, 46.1, 39.2, 35.5, 32.1, 22.5; HRMS (ESI) calcd for C27H25O3 [M + H]+: 397.1804; found: 397.1800.
4-Benzoyl-8a-methyl-3-(thiophen-2-yl)-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3s). Prepared according to the general procedure as described above in 77% yield (61 mg). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.3) to afford a white semi solid; 1H NMR (400 MHz, CDCl3) δ 7.88 (dt, J = 8.5, 1.6 Hz, 2H), 7.59–7.54 (m, 1H), 7.49–7.43 (m, 2H), 7.10 (dd, J = 5.1, 1.2 Hz, 1H), 6.94 (dd, J = 3.5, 1.1 Hz, 1H), 6.90–6.87 (m, 1H), 6.65 (d, J = 10.0 Hz, 1H), 5.99 (dd, J = 10.0, 0.9 Hz, 1H), 4.44–4.38 (m, 1H), 4.07–3.95 (m, 2H), 3.94–3.82 (m, 1H), 2.83 (dd, J = 16.4, 13.7 Hz, 1H), 2.43 (dt, J = 13.7, 4.2 Hz, 1H), 1.98 (ddd, J = 16.3, 4.0, 0.8 Hz, 1H), 1.78 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.7, 197.8, 150.4, 142.5, 135.8, 133.8, 129.2, 128.2, 127.1, 125.6, 123.7, 69.9, 66.6, 48.5, 38.6, 35.2, 33.1, 22.2; HRMS (ESI) calcd for C21H20O3NaS [M + Na]+: 375.1031; found: 375.1029.
4-Benzoyl-3-(dibenzo[b,d]thiophen-4-yl)-8a-methyl-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3t). Prepared according to the general procedure as described above in 65% yield (66 mg). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.3) to afford a pale yellow solid; mp = 286–288 °C; 1H NMR (400 MHz, CDCl3) δ 8.11–8.07 (m, 1H), 7.99 (dd, J = 6.1, 2.9 Hz, 1H), 7.91–7.87 (m, 3H), 7.54 (t, J = 7.4 Hz, 1H), 7.45 (dtd, J = 11.7, 7.3, 3.1 Hz, 4H), 7.39–7.33 (m, 2H), 6.70 (d, J = 10.0 Hz, 1H), 6.04 (dd, J = 10.0, 0.7 Hz, 1H), 4.95 (s, 1H), 4.17–3.94 (m, 3H), 3.01 (dd, J = 16.3, 13.7 Hz, 1H), 2.59 (dt, J = 13.7, 4.2 Hz, 1H), 2.08–2.01 (m, 1H), 1.90 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.8, 197.9, 150.4, 139.0, 136.5, 135.9, 135.6, 134.0, 133.7, 129.2, 129.2, 128.3, 127.1, 125.1, 124.6, 122.9, 121.7, 120.6, 70.1, 64.4, 45.4, 38.8, 37.6, 35.3, 22.6; HRMS (ESI) calcd for C29H25O3S [M + H]+: 453.1524; found: 453.1522.
4-(4-Ethylbenzoyl)-8a-methyl-3-phenyl-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3u). Prepared according to the general procedure as described above in 60% yield (46 mg). It was purified by flash chromatography (20% EtOAc/hexanes; Rf = 0.4) to afford a pale yellow semi solid; 1H NMR (400 MHz, CDCl3) δ 7.81–7.77 (m, 2H), 7.32–7.26 (m, 4H), 7.26–7.23 (m, 2H), 7.18–7.14 (m, 1H), 6.66 (d, J = 10.0 Hz, 1H), 5.99 (dd, J = 10.0, 0.9 Hz, 1H), 4.52 (dd, J = 11.7, 4.4 Hz, 1H), 3.94 (dd, J = 12.1, 5.6 Hz, 1H), 3.82 (t, J = 12.0 Hz, 1H), 3.72–3.61 (m, 1H), 2.88 (dd, J = 16.4, 13.7 Hz, 1H), 2.67 (q, J = 7.6 Hz, 2H), 2.48 (dt, J = 13.6, 4.2 Hz, 1H), 1.98 (ddd, J = 16.3, 4.0, 0.8 Hz, 1H), 1.81 (s, 3H), 1.23 (t, J = 7.6 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 199.0, 197.5, 150.6, 150.4, 139.5, 133.4, 129.0, 128.7, 128.5, 128.3, 127.9, 127.1, 69.8, 66.4, 46.1, 38.7, 37.5, 35.2, 29.0, 22.3, 15.1; HRMS (ESI) calcd for C25H27O3 [M + H]+: 375.1960; found: 375.1963.
4-(4-(tert-Butyl)benzoyl)-8a-methyl-3-phenyl-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3v). Prepared according to the general procedure as described above in 61% yield (45 mg). It was purified by flash chromatography (20% EtOAc/hexanes; Rf = 0.5) to afford a white semi solid; 1H NMR (400 MHz, CDCl3) δ 7.83–7.78 (m, 2H), 7.48–7.43 (m, 2H), 7.31–7.26 (m, 3H), 7.25–7.23 (m, 1H), 7.19–7.14 (m, 1H), 6.66 (d, J = 10.0 Hz, 1H), 5.99 (dd, J = 10.0, 0.8 Hz, 1H), 4.52 (dd, J = 11.7, 4.5 Hz, 1H), 3.94 (dd, J = 12.1, 5.7 Hz, 1H), 3.82 (t, J = 12.0 Hz, 1H), 3.69 (ddd, J = 16.4, 8.1, 3.7 Hz, 1H), 2.88 (dd, J = 16.4, 13.7 Hz, 1H), 2.50 (dt, J = 13.7, 4.2 Hz, 1H), 2.01–1.95 (ddd, J = 16.4, 4.1, 0.8 Hz, 1H), 1.81 (s, 3H), 1.31 (s, 9H); 13C NMR (101 MHz, CDCl3) δ 199.0, 197.4, 157.4, 150.4, 139.5, 133.1, 129.1, 128.7, 128.1, 127.9, 127.1, 126.0, 69.8, 66.4, 46.1, 42.1, 38.7, 37.5, 35.2, 31.0, 22.3; HRMS (ESI) calcd for C27H31O3 [M + H]+: 403.2273; found: 403.2277.
8a-Methyl-3-phenyl-4-(4-(trifluoromethyl)benzoyl)-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3w). Prepared according to the general procedure as described above in 67% yield (49 mg). It was purified by flash chromatography (20% EtOAc/hexanes; Rf = 0.4) to afford a colourless semi solid; 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.1 Hz, 2H), 7.69 (d, J = 8.2 Hz, 2H), 7.27–7.22 (m, 4H), 7.19–7.14 (m, 1H), 6.65 (d, J = 10.0, Hz 1H), 5.99 (dd, J = 10.0, 0.8 Hz, 1H), 4.50 (dd, J = 11.7, 4.4 Hz, 1H), 3.93 (dd, J = 12.2, 5.7 Hz, 1H), 3.82 (t, J = 12, 1H), 3.63 (ddd, J = 11.8, 8.7, 4.4 Hz, 1H), 2.88 (dd, J = 16.3, 13.7 Hz, 1H), 2.42 (dt, J = 13.7, 4.2 Hz, 1H), 1.92 (ddd, J = 16.3, 4.0, 0.8 Hz, 1H), 1.79 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.5, 197.4, 150.4, 139.1, 138.5, 135.0 (q, JCF = 33.0 Hz), 129.2, 129.0, 128.5, 128.0, 127.5, 126.3 (q, JCF = 3.4 Hz), 123.5 (q, JCF = 273.0 Hz), 69.9, 66.3, 46.9, 38.5, 37.6, 35.2, 22.4; 19F NMR (CDCl3) δ −63.26 (s); HRMS (ESI) calcd for C24H22O3F3 [M + H]+: 415.1521; found: 415.1523.
4-([1,1′-Biphenyl]-4-carbonyl)-8a-methyl-3-phenyl-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3x). Prepared according to the general procedure as described above in 92% yield (68 mg). It was purified by flash chromatography (20% EtOAc/hexanes; Rf = 0.4) to afford a pale yellow solid; mp = 227–229 °C; 1H NMR (400 MHz, CDCl3) δ 7.96–7.91 (m, 2H), 7.67–7.63 (m, 2H), 7.59–7.55 (m, 2H), 7.48–7.42 (m, 2H), 7.42–7.36 (m, 1H), 7.34–7.29 (m, 2H), 7.29–7.23 (m, 2H), 7.20–7.14 (m, 1H), 6.67 (d, J = 10.0, 1H), 6.00 (dd, J = 10.0, 0.6 Hz, 1H), 4.58 (dd, J = 11.7, 4.4 Hz, 1H), 3.95 (dd, J = 12.1, 5.7 Hz, 1H), 3.85 (t, J = 12.0 Hz, 1H), 3.68 (td, J = 11.8, 5.6 Hz, 1H), 2.92 (dd, J = 16.4, 13.7 Hz, 1H), 2.53 (dt, J = 13.6, 4.1 Hz, 1H), 2.06–1.99 (ddd, J = 16.4, 4.1, 0.8 Hz, 1H), 1.83 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.9, 197.6, 150.5, 146.4, 139.7, 139.5, 134.4, 129.1 (2C), 128.8 (2C), 128.5, 128.0, 127.8, 127.3, 127.2, 69.9, 66.4, 46.3, 38.7, 37.6, 35.3, 22.4; HRMS (ESI) calcd for C29H27O3 [M + H]+: 423.1960; found: 423.1961.
4-(3-Bromobenzoyl)-8a-methyl-3-phenyl-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3y). Prepared according to the general procedure as described above in 65% yield (48 mg). It was purified by flash chromatography (20% EtOAc/hexanes; Rf = 0.4) to afford a pale yellow semi solid; 1H NMR (500 MHz, CDCl3) δ 7.95 (s, 1H), 7.77 (d, J = 7.6 Hz, 1H), 7.68 (d, J = 7.8 Hz, 1H), 7.38–7.23 (m, 5H), 7.19 (d, J = 5.8 Hz, 1H), 6.67 (d, J = 10.0 Hz, 1H), 6.01 (d, J = 10.0 Hz, 1H), 4.45 (dd, J = 11.7, 4.1 Hz, 1H), 3.94 (dd, J = 12.1, 5.5 Hz, 1H), 3.83 (t, J = 12.0 Hz, 1H), 3.64 (td, J = 11.7, 5.6 Hz, 1H), 2.89 (dd, J = 15.7, 14.3 Hz, 1H), 2.45 (dd, J = 9.8, 3.8 Hz, 1H), 1.94 (dd, J = 16.3, 3.5 Hz, 1H), 1.81 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 198.7, 196.8, 150.4, 139.2, 137.5, 136.6, 131.3, 130.7, 129.2, 128.9, 128.0, 127.4, 126.6, 123.6, 69.9, 66.3, 46.7, 38.6, 37.6, 35.3, 22.4; HRMS (ESI) calcd for C23H22O3Br [M + H]+: 425.0752; found: 425.0757.
4-(3,4-Dichlorobenzoyl)-8a-methyl-3-phenyl-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3z). Prepared according to the general procedure as described above in 68% yield (50 mg). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.6) to afford a pale pink semi solid; 1H NMR (500 MHz, CDCl3) δ 7.89 (d, J = 2.1 Hz, 1H), 7.66 (dd, J = 8.4, 2.0 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.27–7.25 (m, 4H), 7.21–7.16 (m, 1H), 6.66 (d, J = 10.0 Hz, 1H), 6.01 (dd, J = 10.0, 0.9 Hz, 1H), 4.41 (dd, J = 11.8, 4.4 Hz, 1H), 3.94 (dd, J = 12.2, 5.6 Hz, 1H), 3.82 (dd, J = 15.2, 8.9 Hz, 1H), 3.63 (td, J = 11.8, 5.6 Hz, 1H), 2.89 (dd, J = 16.3, 13.7 Hz, 1H), 2.43 (dt, J = 13.7, 4.2 Hz, 1H), 1.92 (ddd, J = 16.3, 4.0, 0.8 Hz, 1H), 1.80 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.5, 196.0, 150.4, 139.1, 138.5, 135.3, 134.0, 131.3, 130.2, 129.2, 129.0, 128.0, 127.5, 127.1, 69.9, 66.3, 46.7, 38.6, 37.7, 35.3, 22.4; HRMS (ESI) calcd for C23H21O3Cl2 [M + H]+: 415.0868; found: 415.0871.
4-(3,4-Dimethylbenzoyl)-8a-methyl-3-phenyl-3,4,4a,5-tetrahydro-2H-chromen-6(8aH)-one (3aa) (inseparable diastereomers). Prepared according to the general procedure as described above in 52% yield (39 mg). It was purified by flash chromatography (20% EtOAc/hexanes; Rf = 0.3) to afford a brown semi solid; 1H NMR (400 MHz, CDCl3) δ 7.64–7.58 (m, 2H), 7.31–7.26 (m, 3H), 7.25–7.23 (m, 1H), 7.20–7.13 (m, 2H), 6.66 (d, J = 10.0, 1H), 5.99 (dd, J = 10.0, 0.8 Hz, 1H), 4.50 (dd, J = 11.7, 4.4 Hz, 1H), 3.94 (dd, J = 12.0, 5.6 Hz, 1H), 3.82 (t, J = 12.0 Hz, 1H), 3.65 (ddd, J = 11.8, 8.7, 5.5 Hz, 1H), 2.87 (dd, J = 16.4, 13.7 Hz, 1H), 2.47 (dt, J = 13.7, 4.2 Hz, 1H), 2.29 (s, 3H), 2.28 (s, 3H), 1.98 (ddd, J = 16.3, 4.0, 0.8 Hz, 1H), 1.80 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 199.1, 197.9, 150.5, 143.4, 139.6, 137.6, 133.8, 130.2, 129.5, 129.2, 128.8, 128.0, 127.2, 125.7, 70.0, 66.5, 46.1, 38.9, 37.6, 35.3, 22.4, 20.2, 20.0; HRMS (ESI) calcd for C25H27O3 [M + H]+: 375.1960; found: 375.1956.
4-Benzoyl-8a-ethyl-3-phenyl-3,4,4a,8a-tetrahydro-2H-chromen-6(5H)-one (3ab). Prepared according to the general procedure as described above in 61% yield (31 mg). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.4) to afford a white solid; mp = 178–180 °C; 1H NMR (500 MHz, CDCl3) δ 7.89–7.81 (m, 2H), 7.59–7.52 (m, 1H), 7.46 (dt, J = 7.4, 6.5 Hz, 2H), 7.31–7.26 (m, 3H), 7.26–7.24 (m,1H), 7.21–7.15 (m, 1H), 6.72 (d, J = 10.2 Hz, 1H), 6.06 (dd, J = 10.2, 0.8 Hz, 1H), 4.50 (dd, J = 11.6, 4.4 Hz, 1H), 3.92 (dd, J = 12.0, 5.5 Hz, 1H), 3.77 (t, J = 12.0 Hz, 1H), 3.67 (td, J = 11.8, 5.5 Hz, 1H), 2.92 (dd, J = 16.3, 13.6 Hz, 1H), 2.55 (dt, J = 13.6, 4.2 Hz, 1H), 2.25(q J = 7.5 Hz, 2H), 1.99 (ddd, J = 16.3, 4.1, 0.8 Hz, 1H), 1.10 (t, J = 7.5 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 198.9, 198.2, 148.6, 139.5, 135.8, 133.6, 130.2, 129.0, 128.7, 128.0, 127.9, 127.1, 72.2, 66.3, 45.9, 37.2, 35.8, 35.1, 26.2, 7.8; HRMS (ESI) calcd for C24H24NaO3 [M + Na]+: 383.1623; found: 383.1628.
4-Benzoyl-8a-isopropyl-3-phenyl-3,4,4a,8a-tetrahydro-2H-chromen-6(5H)-one (3ac). Prepared according to the general procedure as described above in 69% yield (35 mg). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.4) to afford a white solid; mp = 189–191 °C; 1H NMR (400 MHz, CDCl3) δ 7.86 (dd, J = 5.2, 3.3 Hz, 2H), 7.60–7.52 (m, 1H), 7.45 (dd, J = 10.5, 4.7 Hz, 2H), 7.33–7.26 (m, 3H), 7.26–7.23 (m, 1H), 7.20–7.14 (m, 1H), 6.76 (d, J = 10.3 Hz, 1H), 6.10 (d, J = 10.3 Hz, 1H), 4.52 (dd, J = 10.8, 4.5 Hz, 1H), 3.90 (dd, J = 9.8, 3.7 Hz, 1H), 3.71 (dd, J = 10.6, 4.5 Hz, 2H), 3.07 (dt, J = 13.7, 6.8 Hz, 1H), 2.99–2.90 (m, 1H), 2.75 (dt, J = 13.4, 4.1 Hz, 1H), 2.00 (ddd, J = 16.1, 4.0, 0.8 Hz, 1H), 1.19 (d, J = 6.7 Hz, 3H), 1.04 (d, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 198.0, 197.2, 144.5, 138.5, 134.7, 132.5, 130.3, 128.0, 127.7, 127.0, 126.9, 126.1, 73.3, 65.1, 44.5, 35.9, 34.3, 33.5, 26.5, 17.2, 14.1; HRMS (ESI) calcd for C25H26O3Na [M + Na]+: 397.1780; found: 397.1775.
4-Benzoyl-8a-(2-((tert-butyldimethylsilyl)oxy)ethyl)-3-phenyl-3,4,4a,8a-tetrahydro-2H-chromen-6(5H)-one (3ad). Prepared according to the general procedure as described above in 70% yield (16 mg). It was purified by flash chromatography (30% EtOAc/hexanes; Rf = 0.3) to afford a yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.89–7.84 (m, 2H), 7.59–7.51 (m, 1H), 7.44 (t, J = 7.7 Hz, 2H), 7.32–7.27 (m, 3H), 7.26–7.23 (m, 1H), 7.19–7.14 (m, 1H), 6.86 (d, J = 10.2 Hz, 1H), 6.03 (dd, J = 10.0, 0.7 Hz, 1H), 4.53 (dd, J = 11.6, 4.4 Hz, 1H), 3.96–3.84 (m, 3H), 3.80 (t, J = 11.9 Hz, 1H), 3.67 (td, J = 11.7, 5.5 Hz, 1H), 2.90 (dd, J = 16.3, 13.6 Hz, 1H), 2.60 (dt, J = 13.7, 4.3 Hz, 1H), 2.48 (td, J = 6.8, 3.6 Hz, 2H), 1.99 (dd, J = 16.0, 3.8 Hz, 1H), 0.91 (s, 9H), 0.09 (s, 3H), 0.08 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 198.7, 198.2, 148.7, 139.4, 135.9, 133.5, 129.5, 129.0, 128.7, 128.1, 127.9, 127.2, 71.3, 66.5, 58.6, 46.0, 37.3, 36.7, 36.6, 35.2, 26.0, 18.4, −5.3; HRMS (ESI) calcd for C30H38NaSiO4 [M + Na]+: 513.2437; found: 513.2451.
4-Benzoyl-3-phenyloctahydrofuro[2,3-i]chromen-6(2H)-one (8). To a stirred solution of silyl ether 3ab (20 mg, 0.04 mmol) in anhydrous THF (2 mL) was added TBAF (12 μL, 1.0 M in THF, 0.04 mmol) at 0 °C and then stirred for 1 hour at room temperature. After completion of the reaction (monitored by TLC), the reaction solvent was evaporated in vacuo, and then the residue was purified by flash column chromatography (40% EtOAc/hexane; Rf = 0.3) to give oxa-Michael product 8 (12 mg, 80% yield) as a white semi solid; 1H NMR (500 MHz, CDCl3) δ 7.89–7.82 (m, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.8 Hz, 2H), 7.26 (d, J = 0.6 Hz, 2H), 7.26–7.25 (m, 2H), 7.24–7.12 (m, 1H), 4.37 (dd, J = 11.1, 4.2 Hz, 1H), 4.06 (dtd, J = 11.6, 9.2, 5.5 Hz, 4H), 3.74–3.62 (m, 2H), 2.78–2.69 (m, 2H), 2.57 (ddd, J = 12.9, 7.8, 5.2 Hz, 1H), 2.51–2.41 (m, 2H), 2.37 (dt, J = 12.4, 7.5 Hz, 1H), 1.93 (ddd, J = 16.4, 4.1, 0.8 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 208.5, 198.0, 139.3, 135.8, 133.8, 129.2, 128.9, 128.2, 128.0, 127.4, 82.9, 81.4, 69.4, 66.1, 46.8, 42.3, 37.9, 37.0, 34.2, 31.1; HRMS (ESI) calcd for C24H25O4 [M + H]+: 377.1753; found: 377.1749.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

SBJ thanks the University Grants Commission, New Delhi and SBT thanks the Council of Scientific and Industrial Research (CSIR), New Delhi for a research fellowship. RB thanks SERB and CSIR-IICT for financial support.

References

  1. (a) B. M. Trost, F. D. Toste and A. B. Pinkerton, Chem. Rev., 2001, 101, 2067–2096 CrossRef CAS; (b) A. Alexakis, J. E. Bäckvall, N. Krause, O. Pàmies and M. Diéguez, Chem. Rev., 2008, 108, 2796–2823 CrossRef CAS; (c) J. T. Mohr, M. R. Krout and B. M. Stoltz, Nature, 2008, 455, 323–332 CrossRef CAS; (d) Q. Liu, R. Jackstell and M. Beller, Angew. Chem., Int. Ed., 2013, 52, 13871–13873 CrossRef CAS; (e) T. Tsubogo, T. Ishiwata and S. Kobayashi, Angew. Chem., Int. Ed., 2013, 52, 6590–6604 CrossRef CAS; (f) C. M. R. Volla, I. Atodiresei and M. Rueping, Chem. Rev., 2014, 114, 2390–2431 CrossRef CAS; (g) N. G. Schmidt, E. Eger and W. Kroutil, ACS Catal., 2016, 6, 4286–4311 CrossRef CAS.
  2. (a) W. Sun, G. Li, L. Hong and R. Wang, Org. Biomol. Chem., 2016, 14, 2164–2176 RSC; (b) K. A. Kalstabakken and A. M. Harned, Tetrahedron, 2014, 70, 9571–9585 CrossRef CAS. For recent review on enantioselective desymmetrization reactions, see: (c) X.-P. Zeng, Z.-Y. Cao, Y.-H. Wang, F. Zhou and J. Zhou, Chem. Rev., 2016, 116, 7330–7396 CrossRef CAS.
  3. For Pd-catalyzed enantioselective desymmetrization of cyclohexadienones to access cis-hydrobenzofuranones, see: (a) K. Takenaka, S. C. Mohanta and H. Sasai, Angew. Chem., Int. Ed., 2014, 53, 4675–4679 CrossRef CAS. For other Pd-catalyzed desymmetrizations, see: (b) K. Kondo, M. Sodeoka, M. Mori and M. Shibasaki, Tetrahedron Lett., 1993, 34, 4219–4222 CrossRef CAS; (c) R. Imbos, A. J. Minnaard and B. L. Feringa, J. Am. Chem. Soc., 2002, 124, 184–185 CrossRef CAS; (d) R. Tello-Aburto and A. M. Harned, Org. Lett., 2009, 11, 3998–4000 CrossRef CAS; (e) C. He, C. Zhu, Z. Dai, C.-C. Tseng and H. Ding, Angew. Chem., Int. Ed., 2013, 52, 13256–13260 CrossRef CAS.
  4. For Cu-catalyzed enantioselective desymmetrization of cyclohexadienones to access cis-hydrobenzofuranones, see: (a) P. Liu, Y. Fukui, P. Tian, Z.-T. He, C.-Y. Sun, N.-Y. Wu and G.-Q. Lin, J. Am. Chem. Soc., 2013, 135, 11700–11703 CrossRef CAS; (b) Z.-T. He, X.-Q. Tang, L.-B. Xie, M. Cheng, P. Tian and G.-Q. Lin, Angew. Chem., Int. Ed., 2015, 54, 14815–14818 CrossRef CAS. For other Cu-catalyzed desymmetrizations, see: (c) B. L. Feringa, M. Pineschi, L. A. Arnold, R. Imbos and A. H. M. de Vries, Angew. Chem., Int. Ed. Engl., 1997, 36, 2620–2623 CrossRef CAS; (d) R. Imbos, M. H. G. Brilman, M. Pineschi and B. L. Feringa, Org. Lett., 1999, 1, 623–626 CrossRef CAS; (e) R. Imbos, A. J. Minnaard and B. L. Feringa, Tetrahedron, 2001, 57, 2485–2489 CrossRef CAS; (f) A. C. Meister, P. F. Sauter and S. Bräse, Eur. J. Org. Chem., 2013, 7110–7116 CrossRef CAS.
  5. For Rh-catalyzed enantioselective desymmetrization of cyclohexadienones to access cis-hydrobenzofuranones, see: (a) J. Keilitz, S. G. Newman and M. Lautens, Org. Lett., 2013, 15, 1148–1151 CrossRef CAS; (b) Z.-T. He, B. Tian, Y. Fukui, X. Tong, P. Tian and G.-Q. Lin, Angew. Chem., Int. Ed., 2013, 52, 5314–5318 CrossRef CAS. For other Rh-catalyzed desymmetrizations, see: (c) F. Guo, L. C. Konkol and R. J. Thomson, J. Am. Chem. Soc., 2011, 133, 18–20 CrossRef CAS; (d) Y. Fukui, P. Liu, Q. Liu, Z.-T. He, N.-Y. Wu, P. Tian and G.-Q. Lin, J. Am. Chem. Soc., 2014, 136, 15607–15614 CrossRef CAS; (e) S. Kress, T. Johnson, F. Weisshar and M. Lautens, ACS Catal., 2016, 6, 747–750 CrossRef CAS.
  6. For other transition metal catalyzed desymmetrization of cyclohexadienones, see: (a) S.-Y. Cai, Z. Liu, W.-B. Zhang, X.-Y. Zhao and D. Z. Wang, Angew. Chem., Int. Ed., 2011, 50, 11133–11137 CrossRef CAS PubMed; (b) C. Clarke, C. A. Incerti-Pradillos and H. W. Lam, J. Am. Chem. Soc., 2016, 138, 8068–8071 CrossRef CAS; (c) R. Kumar, Y. Hoshimoto, E. Tamai, M. Ohashi and S. Ogoshi, Nat. Commun., 2017, 8, 32 CrossRef.
  7. K. K. Gollapelli, S. Donikela, N. Manjula and R. Chegondi, ACS Catal., 2018, 8, 1440–1447 CrossRef CAS.
  8. (a) A. S. Murthy, S. Donikela, C. S. Reddy and R. Chegondi, J. Org. Chem., 2015, 80, 5566–5571 CrossRef CAS PubMed; (b) S. Kallepu, K. K. Gollapelli, J. B. Nanubolu and R. Chegondi, Chem. Commun., 2015, 51, 16840–16843 RSC; (c) K. K. Gollapelli, S. Kallepu, N. Govindappa, J. B. Nanubolu and R. Chegondi, Chem. Sci., 2016, 7, 4748–4753 RSC; (d) L. N. Chavan, K. K. Gollapelli, R. Chegondi and A. B. Pawar, Org. Lett., 2017, 19, 2186–2189 CrossRef CAS; (e) R. R. Anugu and R. Chegondi, J. Org. Chem., 2017, 82, 6786–6794 CrossRef CAS.
  9. For selected examples of Rh-catalyzed enone conjugate addition, see: (a) M. Sakai, H. Hayashi and N. Miyaura, Organometallics, 1997, 16, 4229–4231 CrossRef CAS; (b) Y. Takaya, M. Ogasawara, T. Hayashi, M. Sakai and N. Miyaura, J. Am. Chem. Soc., 1998, 120, 5579–5580 CrossRef CAS; (c) Y. Takaya, M. Ogasawara and T. Hayashi, Tetrahedron Lett., 1998, 39, 8479–8482 CrossRef CAS; (d) S. Sakuma, M. Sakai, R. Itooka and N. Miyaura, J. Org. Chem., 2000, 65, 5951–5955 CrossRef CAS; (e) S. Sakuma and N. Miyaura, J. Org. Chem., 2001, 66, 8944–8946 CrossRef CAS; (f) T. Hayashi, M. Takahashi, Y. Takaya and M. Ogasawara, J. Am. Chem. Soc., 2002, 124, 5052–5058 CrossRef CAS; (g) K. Yoshida, M. Ogasawara and T. Hayashi, J. Am. Chem. Soc., 2002, 124, 10984–10985 CrossRef CAS; (h) D. F. Cauble, J. D. Gipson and M. J. Krische, J. Am. Chem. Soc., 2003, 125, 1110–1111 CrossRef CAS; (i) B. M. Bocknack, L.-C. Wang and M. J. Krische, Proc. Natl. Acad. Sci. U. S. A., 2004, 101, 5421–5424 CrossRef CAS. For a review on Rh-catalyzed enantioselective enone conjugate addition, see: T. Hayashi, Synlett, 2001, 879–887 CrossRef CAS.
  10. CCDC – 1866550 (compound 3t) contains the supplementary crystallographic data for this paper.

Footnotes

CSIR-IICT Manuscript Communication Number: IICT/Pubs./2018/274
Electronic supplementary information (ESI) available: Copies of 1H, 13C NMR spectra for all new compounds, 19F NMR spectra for all fluorinated compounds, and X-ray crystallographic data (CIF file) of compound 3t. CCDC 1866550. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c8ob02284d
§ These authors contributed equally to this work.

This journal is © The Royal Society of Chemistry 2019