View PDF VersionPrevious ArticleNext Article
 
DOI: 10.1039/C3RA47773H (Paper) RSC Adv., 2014, 4, 17218-17221

Diastereoselection during 1,2-addition of 3-bromomethyl-5H-furan-2-one to α-chiral aldehydes mediated by indium in aqueous and organic solvent systems: direct route to obtain optically active α-methylene-γ-butyrolactones†

Fuhai Zhang, Yang Liu, Longguan Xie and Xiaohua Xu*
State Key Laboratory of Elemento-Organic Chemistry, Collaborative innovation center of chemical science and engineering, Nankai University, Tianjin 300071, China. E-mail: xiaohuaxu@nankai.edu.cn; Fax: +86 22 23502737; Tel: +86 22 23502723

Received 19th December 2013 , Accepted 18th February 2014

First published on 18th February 2014

Abstract

The stereochemical course of indium-promoted allylations to α-chiral aldehydes with 3-bromomethyl-5H-furan-2-one was investigated in anhydrous THF and pure H2O. High levels of 3,4-syn;4,5-syn diastereomers were produced with free hydroxyl derivatives whether in THF or pure H2O, reflecting the promising synthetic potential of this chemistry. This stereo-differentiation was attributed to the strong geometric bias exercised by our allylindium reagent and adherence to a chelation control transition-state alignment. Meanwhile, heightened levels of 3,4-anti;4,5-anti diastereomers were obtained with the rigid aldehydes 1h and 1i.

The Cram rule,1 which was put forward about six decades ago as a predictor of the stereochemical course of nucleophilic addition to acyclic aldehydes and ketones, has incited organic chemists into thinking systematically about diastereomeric transition states. As a consequence of complications introduced by the dynamic conformational nature of substrates, bearing stereogenic centers proximal to the carbonyl group, other researchers have presented paradigms in which the interplay of steric and stereoelectronic effects has been somewhat modified.2–4 However, all Cram and Felkin–Ahn paradigms have been founded in anhydrous conditions because of the sensitivity of organometallic reagents to moisture before indium metal was found to be capable of promoting carbon–carbon bond-forming reactions in water. Subsequently, Paquette and his co-workers established the levels of stereocontrol attainable in aqueous environments when a neighboring heteroatom is present, clarifying competitive intramolecular/intermolecular chelation options.5 When chelation occurs, the reaction diastereoselection is controlled by intramolecular delivery from the less sterically hindered π-face of the preformed complex. In substrates lacking the potential for chelate organization, the interplay of steric and electronic forces summed up in the Felkin–Ahn model3 provides a useful stereoinduction paradigm. Studies in these laboratories have addressed the applicability of the above criteria to indium-mediated coupling reactions in water.

Optically α-methylene-γ-butyrolactones are an interesting class of compounds because of their intrinsic reactivity, as shown by their use as chiral building blocks for the synthesis of natural products, such as alkaloids, macrocyclic antibiotics, lignan lactones and pheromones,6 as well as their occurrence in a large variety of natural products and biologically active compounds (Fig. 1).7,8 The physiological activity of these α-methylene-γ-butyrolactones often depends on their enantiomeric purity and absolute configurations.9 Therefore, many methods have been developed for the synthesis of functionalized α-methylene-γ-butyrolactone derivatives in an optically active form.10


image file: c3ra47773h-f1.tif
Fig. 1 Representative α-methylene-γ-butyrolactones.

Our continued investigation of Barbier coupling reactions involving 3-bromomethyl-5H-furan-2-one (2)11–14 and the desirability of producing α-methylene-γ-butyrolactone derivatives in an optically active form prompted us to extensively examine the condensation of α-chiral aldehydes (1a–i) with 3-bromomethyl-5H-furan-2-one (2). In the illustrated example15 where R′ was methyl (Scheme 1, 1-1), no anti,syn product was generated; instead, syn,syn; syn,anti and anti,anti diastereomers were afforded rather indiscriminately. Further erosion of stereocontrol occurred when R′ was bromine. In this instance, all four possible alcohols were produced. The lack of stereocontrol in these circumstances was attributed to facile E/Z equilibration within the relevant indium reagents, as established previously for the related Grignard, potassium, and lithium derivatives. However, excellent stereocontrol (only syn) was obtained for methyl (Z)-2-(bromomethyl)-2-butenoate, which possesses a greater thermodynamic stability than the E alternative (Scheme 1, 1-2).16 In this report, we further confirmed the feasibility of setting three contiguous stereogenic centers in a highly controlled fashion under aqueous conditions with α-hydroxyaldehydes or rigid aldehydes, through which we can obtain functionalized α-methylene-γ-butyrolactone derivatives in high diastereoselectivity. This finding is not only ascribed to Felkin–Ahn or chelation-control transition states, but also to the persistence of a single (E)-geometry organoindium intermediate of 3-bromomethyl-5H-furan-2-one (2).


image file: c3ra47773h-s1.tif
Scheme 1 Indium-mediated coupling of allylic bromide to α-oxygenated aldehydes in water.

image file: c3ra47773h-s2.tif
Scheme 2 Michael addition reaction of 11–14g obtained from entry 13.

In an effort to vary the basicity of the α-oxy substituent and its steric environment to reasonable levels, five substrates 1a–e were examined (Table 1). The preparation of 1a–e was adapted from the existing literature. 3-Bromomethyl-5H-furan-2-one (2) was prepared according to the method developed in our laboratory.12 The allylation of 1a–e was conducted at room temperature in pure H2O and anhydrous THF. Consistent with our previous report,13 the quantities of the reagents were regulated to conform to an aldehyde/indium powder/allyl bromide ratio of 1.0[thin space (1/6-em)]:[thin space (1/6-em)]2.0[thin space (1/6-em)]:[thin space (1/6-em)]1.5. The results were not as good as those obtained from the condensation of methyl (Z)-2-(bromomethyl)-2-butenoate with 1a.16 Hardly any π-facial discrimination was observed in the Felkin–Ahn transition state when the allylation of 1a with (2) was conducted (Table 1, entries 1 and 2). The product distributions were quantified by comparison with the literature16 and analysis of the coupling constant (for 7a, J3–4 = 10.6, J4–5 = 2.4). The considerably extended reaction time required for the allylation performed with THF constituted a trend that was observed throughout this study. 3,4-anti;4,5-syn Diastereomers 7b improved as the size of R1 in aldehyde 1a was amplified from methyl to phenyl (Table 1, entries 3 and 4). When the substituent was OTBDPS, the preferred diastereofacile selectivity of the reaction was reversed to 4,5-anti (Table 1, entries 7 and 8). The results indicate that larger groups (R2), such as tert-butyldimethylsilyl and tert-butyldiphenylsilyl, effectively deterred transient binding of the attached oxygen to the indium, at least in water, and promoted alternative conversion to the product via a Felkin–Ahn transition state. Thus, steric effects appeared to exert a significant influence on the outcome of these single asymmetric induction processes. The diastereoselectivity between C-3 and C-4 can be explained by six-membered cyclic transition state C (Fig. 2). However, when R2 was benzyl, which possesses some chelating abilities, the product distribution became more complicated and a relatively low level of both simple (anti/syn) diastereoselectivity and distereofacial selectivity was obtained (Table 1, entries 9–10).

Table 1 Indium-mediated coupling of 2 to α-oxygenated aldehydes 1a–e in H2O or THF, 25 °Ca

image file: c3ra47773h-u1.tif
Entry Aldehyde Solvent Time (h) Yieldb (%) 7[thin space (1/6-em)]:[thin space (1/6-em)]8[thin space (1/6-em)]:[thin space (1/6-em)]9[thin space (1/6-em)]:[thin space (1/6-em)]10c
a All reactions were conducted at least in duplicate at a concentration of 0.1 M with vigorous stirring for the indicated time span.b Isolated yields by flash column chromatography.c The product proportions in all cases were determined by 1H NMR integration at 400 MHz.
1 image file: c3ra47773h-u2.tif H2O 12 75.6 1.2[thin space (1/6-em)]:[thin space (1/6-em)]1[thin space (1/6-em)]:[thin space (1/6-em)]0[thin space (1/6-em)]:[thin space (1/6-em)]0
2 THF 30 77.0 0.8[thin space (1/6-em)]:[thin space (1/6-em)]1[thin space (1/6-em)]:[thin space (1/6-em)]0[thin space (1/6-em)]:[thin space (1/6-em)]0
3 image file: c3ra47773h-u3.tif H2O 12 80.0 4.0[thin space (1/6-em)]:[thin space (1/6-em)]1[thin space (1/6-em)]:[thin space (1/6-em)]0[thin space (1/6-em)]:[thin space (1/6-em)]0
4 THF 30 75.0 2.5[thin space (1/6-em)]:[thin space (1/6-em)]1[thin space (1/6-em)]:[thin space (1/6-em)]0[thin space (1/6-em)]:[thin space (1/6-em)]0
5 image file: c3ra47773h-u4.tif H2O 12 79 2.0[thin space (1/6-em)]:[thin space (1/6-em)]1[thin space (1/6-em)]:[thin space (1/6-em)]0[thin space (1/6-em)]:[thin space (1/6-em)]0
6 THF 30 75.4 1.5[thin space (1/6-em)]:[thin space (1/6-em)]1[thin space (1/6-em)]:[thin space (1/6-em)]0[thin space (1/6-em)]:[thin space (1/6-em)]0
7 image file: c3ra47773h-u5.tif H2O 12 78.2 1[thin space (1/6-em)]:[thin space (1/6-em)]1.2[thin space (1/6-em)]:[thin space (1/6-em)]0[thin space (1/6-em)]:[thin space (1/6-em)]0
8 THF 30 76.0 1[thin space (1/6-em)]:[thin space (1/6-em)]2.0[thin space (1/6-em)]:[thin space (1/6-em)]0[thin space (1/6-em)]:[thin space (1/6-em)]0
9 image file: c3ra47773h-u6.tif H2O 8 80.5 0.55[thin space (1/6-em)]:[thin space (1/6-em)]1[thin space (1/6-em)]:[thin space (1/6-em)]0[thin space (1/6-em)]:[thin space (1/6-em)]0.4
10 THF 24 71.0 0.7[thin space (1/6-em)]:[thin space (1/6-em)]1[thin space (1/6-em)]:[thin space (1/6-em)]0[thin space (1/6-em)]:[thin space (1/6-em)]0.75


image file: c3ra47773h-f2.tif
Fig. 2 Transition state model analysis.

The next series of experiments was performed with the unprotected α-hydroxyaldehydes and two rigid aldehydes (Table 2). Heavy predominance of the 3,4-syn;4,5-syn diastereomers 13f and 13g occurred when the series of experiments was performed with α-hydroxy aldehydes 1f and 1g whether in THF or in pure H2O (Table 1, entries 11–14). This result indicates a high chelation control transition state preference in the carbonyl reagent.17,18 However, the diastereoselectivity was decreased to 1.26[thin space (1/6-em)]:[thin space (1/6-em)]1 (7[thin space (1/6-em)]:[thin space (1/6-em)]8, Table 1) when the hydroxy of 1f was protected with tert-butyldimethylsilyl chloride. It was established that the α-hydroxy was fundamental for the selectivity.

Table 2 Indium-mediated coupling of 2 to α-oxygenated aldehydes 1f–i in H2O or THF, 25 °Ca

image file: c3ra47773h-u7.tif
Entry Aldehyde Solvent Time (h) Yieldb (%) 11[thin space (1/6-em)]:[thin space (1/6-em)]12[thin space (1/6-em)]:[thin space (1/6-em)]13[thin space (1/6-em)]:[thin space (1/6-em)]14c
a All reactions were conducted at least in duplicate at a concentration of 0.1 M with vigorous stirring for the indicated time span.b Isolated yields by flash column chromatography.c The product proportions in all cases were determined by 1H NMR integration at 400 MHz.
11 image file: c3ra47773h-u8.tif H2O 6 79.2 0.08[thin space (1/6-em)]:[thin space (1/6-em)]0.07[thin space (1/6-em)]:[thin space (1/6-em)]1[thin space (1/6-em)]:[thin space (1/6-em)]0.02
12 THF 18 72.0 0.06[thin space (1/6-em)]:[thin space (1/6-em)]0[thin space (1/6-em)]:[thin space (1/6-em)]1[thin space (1/6-em)]:[thin space (1/6-em)]0.02
13 image file: c3ra47773h-u9.tif H2O 6 85 0.05[thin space (1/6-em)]:[thin space (1/6-em)]0.03[thin space (1/6-em)]:[thin space (1/6-em)]1[thin space (1/6-em)]:[thin space (1/6-em)]0.01
14 THF 18 72 0.04[thin space (1/6-em)]:[thin space (1/6-em)]0.06[thin space (1/6-em)]:[thin space (1/6-em)]1[thin space (1/6-em)]:[thin space (1/6-em)]0.01
15 image file: c3ra47773h-u10.tif H2O 16 87.4 0[thin space (1/6-em)]:[thin space (1/6-em)]13[thin space (1/6-em)]:[thin space (1/6-em)]1[thin space (1/6-em)]:[thin space (1/6-em)]1.3
16 image file: c3ra47773h-u11.tif H2O 12 70.0 Only 12i

As anticipated, direct determination of the relative stereochemistry of the four diastereomers from the 1H and 13C NMR spectra was not possible. Fortunately, the major derivative 13g′, which was crystalline, can be isolated by column chromatography (Scheme 2). Consequently, single-crystal X-ray analyses revealed its absolute configuration (see ESI†). This result was attributed to chelation control transition-state alignment A (Fig. 2). The distribution of 11g, 12g and 14g was determined by a comparison with the literature15 and our experimental observations. In addition, during the Michael addition reaction, we isolated a small amount of the transesterification product 13g′′, whose absolute configuration was also determined by single-crystal X-ray analyses (see ESI†).

Given their shorter reaction time in water, aldehydes 1h and 1i were examined only under aqueous conditions (entries 15 and 16). Heavy predominance of the 3,4-anti;4,5-anti diastereomer 12h was obtained with aldehyde 1h according to the Felkin–Ahn transition state. Flash chromatography on silica gel resulted in the separation of a 10[thin space (1/6-em)]:[thin space (1/6-em)]1 mixture of 12h and 14h from 3,4-syn;4,5-syn diastereomer 13h. The absolute configuration of the major product 12h was determined by single-crystal X-ray analyses of 12h′ (see ESI†), which was obtained the same way as in Scheme 2 so that we could define the absolute configurations of 13h and 14h through a comparison of the coupling constants of J3–4 and J4–5 with 12h (for 12h, J4–5 = 11.2, J3–4 = 13.6; for 13h, J4–5 = 6.8, J3–4 = 8.4; for 14h, J4–5 = 11.2). To our surprise, only 3,4-anti;4,5-anti diastereomer 12i was obtained with rigid aldehyde 1i. These results can be ascribed to the six-membered cyclic transition state B and Felkin–Ahn transition state C (Fig. 2).

Subsequently, we studied the effects of salt in the allylation reaction of hydroxyaldehyde 1g with (2) (Table 3). For Diels–Alder cycloadditions performed in water, the presence of salts increased the amount of endo products due to an increase in the internal pressure of the system.19 Were the reaction volumes for the formation of the syn and anti homoallylic alcohols to differ comparably, the possibility exists that the product ratios can be conveniently manipulated to a synthetic advantage in this manner. When 1g was admixed with 1.0 mol equivalent of LiBr or MgCl2 and subjected to conventional allylation in H2O, the diastereofacial selectivities (syn/anti) declined somewhat to 18[thin space (1/6-em)]:[thin space (1/6-em)]1 in both cases (Table 3, entries 17 and 18). Moreover, the use of tetraethylammonium bromide resulted in a substantial decrease to a record level of 7.2[thin space (1/6-em)]:[thin space (1/6-em)]1 (entry 19). Although the proportion of 11g increased to some extent (Table 3, entries 20 and 21), it affected the average selectivities. In fact, the lithium and magnesium halides performed less well than the quaternary salt.

Table 3 Effects of salt on indium-promoted allylation in water at 25 °Ca
Entry Aldehyde Added salt (no of equiv.) Time (h) Yield (%)b 11g[thin space (1/6-em)]:[thin space (1/6-em)]12g[thin space (1/6-em)]:[thin space (1/6-em)]13g[thin space (1/6-em)]:[thin space (1/6-em)]14g
a All reactions were performed at least in duplicate with vigorous stirring.b Isolated yields by flash column chromatography.
17 image file: c3ra47773h-u12.tif LiBr(1.0) 6 78.7 0.08[thin space (1/6-em)]:[thin space (1/6-em)]0.04[thin space (1/6-em)]:[thin space (1/6-em)]1.0[thin space (1/6-em)]:[thin space (1/6-em)]0.02
18 MgCl2(1.0) 6 79.2 0.08[thin space (1/6-em)]:[thin space (1/6-em)]0.03[thin space (1/6-em)]:[thin space (1/6-em)]1.0[thin space (1/6-em)]:[thin space (1/6-em)]0.03
19 Et4NBr(1.0) 6 76.2 0.08[thin space (1/6-em)]:[thin space (1/6-em)]0.13[thin space (1/6-em)]:[thin space (1/6-em)]1.0[thin space (1/6-em)]:[thin space (1/6-em)]0.02
20 (n-Bu)4NBr(1.0) 6 88.6 0.2[thin space (1/6-em)]:[thin space (1/6-em)]0.03[thin space (1/6-em)]:[thin space (1/6-em)]1.0[thin space (1/6-em)]:[thin space (1/6-em)]0.03
21 (n-Bu)4NBr(1.0) 6 80.5 0.18[thin space (1/6-em)]:[thin space (1/6-em)]0.03[thin space (1/6-em)]:[thin space (1/6-em)]1.0[thin space (1/6-em)]:[thin space (1/6-em)]0.03

Conclusions

We confirmed that highly functionalized acyclic molecules containing three contiguous stereogenic centers can be assembled with high stereoselectivity from simple building blocks using water as the reaction medium. As the geometry inherent in the allylindium reagent of (2) was biased strongly towards the E configuration, control of product stereochemistry as in 12 or 13 can be expected to operate at synthetically practical levels with α-hydroxyaldehydes or α-rigid aldehydes, respectively. Meanwhile, we provided a highly efficient and convenient method to establish functionalized α-methylene-γ-butyrolactone derivatives in optically active forms. Further application in the total synthesis of optically natural products with this type of substitution is currently under investigation.

Notes and references

  1. D. J. Cram and R. A. Abd Elhafez, J. Am. Chem. Soc., 1952, 74, 5828 CrossRef CAS.
  2. G. J. Karabatsos, J. Am. Chem. Soc., 1967, 89, 1367 CrossRef CAS.
  3. M. Cherest, H. Felkin and N. Prudent, Tetrahedron Lett., 1968, 2199 CrossRef CAS.
  4. N. T. Ahn and O. Eisenstein, Nouv. J. Chim., 1977, 1, 61 Search PubMed.
  5. L. A. Paquette, Synthesis, 2003, 765–774 CrossRef CAS PubMed.
  6. H. C. Brown, S. V. Kulkarni and U. S. Racherla, J. Org. Chem., 1994, 59, 365 CrossRef CAS and refs cited therein.
  7. M. B. de Azevedo, M. M. Murta and A. E. Greene, J. Org. Chem., 1992, 57, 4567 CrossRef CAS and refs cited therein.
  8. V. Andrea and H. Judit, Nat. Prod. Rep., 2011, 28, 824 RSC.
  9. R. M. Silverstein. in Semiochemistry, Flavors and Pheromones; Proceeding ACS Symposium, ed. T. E. Acree, W. de Gruyter and Co., Berlin, 1985, p. 121 Search PubMed.
  10. S. S. C. Koch and A. R. Chamberlin, J. Org. Chem., 1993, 58, 2725 CrossRef CAS and refs cited therein.
  11. H. S. Yang, X. X. Qiao, Q. Cui and X. H. Xu, Chin. Chem. Lett., 2009, 20, 1023–1024 CrossRef CAS PubMed.
  12. H. S. Yang, Y. Z. Gao, X. X. Qiao, L. G. Xie and X. H. Xu, Org. Lett., 2011, 13, 3670–3673 CrossRef CAS PubMed.
  13. Y. Z. Gao, X. Wang, L. Sun, L. G. Xie and X. H. Xu, Org. Biomol. Chem., 2012, 10, 3991 CAS.
  14. F. Zhang, Y. Yang, L. G. Xie and X. H. Xu, Chem. Commun., 2013, 49, 4697–4699 RSC.
  15. L. A. Paquette and T. M. Mitzel, J. Org. Chem., 1996, 61, 8799 CrossRef CAS PubMed.
  16. L. A. Paquette and M. B. Isaac, J. Org. Chem., 1997, 62, 5333–5338 CrossRef.
  17. L. A. Paquette and T. M. Mitzel, J. Am. Chem. Soc., 1996, 118, 1931–1937 CrossRef CAS.
  18. L. A. Paquette and P. C. Lobben, J. Org. Chem., 1998, 63, 5604–5616 CrossRef CAS.
  19. U. Pindur, G. Lutz and G. Otto, Chem. Rev., 1993, 93, 741 CrossRef CAS.

Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c3ra47773h
This journal is © The Royal Society of Chemistry 2014