The fluorine-containing π-allylmetal complex. The transition metal-catalyzed allylic substitution reaction of fluorinated allyl mesylates with various carbon nucleophiles

Abstract

The allylic substitution reaction of α-fluoroalkylated allyl mesylates with various carbon nucleophiles in the presence of transition metal catalyst (Pd and Mo) proceeded with high regioselectivity to give the corresponding γ-fluoroalkylated products in excellent yields.

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Introduction

Transition metal-catalyzed allylic substitution is one of the most efficient and the most versatile methods for carbon–carbon and carbon–heteroatom bond formation, and hence is the focus of intense synthetic attention.¹ To date, considerable effort has been devoted to the development of more efficient reactions catalyzed by various transition metals such as palladium,² molybdenum,³ tungsten,⁴ iridium,⁵ rhodium,⁶ ruthenium,⁷etc. As a result, a number of reactions are available today which very often afford high regio- and stereo-selectivity. In contrast to the remarkable progress made for the reaction of non-fluorinated allylic substrates, little attention has been paid to the transition metal-catalyzed allylic substitution reaction of fluorine-containing allylic esters so far. There have been quite limited studies on the allylic substitution reaction in fluorine chemistry.⁸ Recently, we have reported that the reaction of α-fluoroalkylated allyl mesylates with various carboxylates and amines in the presence of palladium catalyst proceeds in a highly regio- and stereo-selective fashion to give the corresponding γ-products, allylic alcohol or amine derivatives in excellent yields, respectively⁹ (Scheme 1).

Scheme 1

Herein we wish to report an extension of our studies to the allylic substitution reaction of fluorine-containing allylic mesylates with various carbon nucleophiles in detail (Scheme 2).

Scheme 2

Results and discussion

We initially examined the reaction of α-trifluoromethylated allyl mesylate 1a with diethyl sodiomalonate 2a using various palladium catalysts as listed in Table 1.¹⁰ It was found that the ligand on palladium played an important role in the present allylic substitution reaction. Thus, the use of Pd₂(dba)₃·CHCl₃ resulted in the complete recovery of the starting material. In contrast, the addition of various monodentate ligands such as triphenylphosphine, tri(2-furyl)phosphine, triphenyl phosphite, tributylphosphine, and t-octyl isocyanide was found to facilitate the reaction remarkably (entries 2–10). Additionally, the ratio of palladium and the ligand was crutial for effecting the high yield (entries 2–6). It was found that the palladium complexes which were prepared from palladium(0) species and triphenylphosphine in a ratio of 4 : 1, gave the corresponding allylic substitution product 3a-E in excellent yields (entry 4–6). On the other hand, bulky ligands such as (o-Tol)₃P did not provide the desired product at all (entry 8). Changing the ligand on palladium into a bidentate ligand such as dppe, dppf, and bpy caused a large decrease in the formation of 3a-E (entries 9–11). In all cases, neither γ-Z-product 3a-Z nor α-E or Z-products 4a-E, 4a-Z were detected (Fig. 1).¹¹

Table 1 Investigation of the effect of the ligands

Entry	Catalyst	Yield of 3a-E (%)^a	Unreacted 1a (%)^a
a Determined by ^19F NMR. Value in parentheses is of isolated yield.b A diene was produced in 16% yield.c A diene was formed in 8% yield (see Scheme 3).
1	1/2[Pd2(dba)3·CHCl3]	0	96
2	1/2[Pd2(dba)3·CHCl3] + PPh3	38^b	44
3	1/2[Pd2(dba)3·CHCl3] + 2PPh3	82^c	0
4	1/2[Pd2(dba)3·CHCl3] + 4PPh3	90	0
5	Pd(OAc)2 + 5PPh3	93	0
6	Pd(PPh3)4	(99)	0
7	1/2[Pd2(dba)3·CHCl3] + 4P(2-furyl)3	87	0
8	1/2[Pd2(dba)3·CHCl3] + 4P(OPh)3	61	32
9	1/2[Pd2(dba)3·CHCl3] + 4P(n-Bu)3	52	46
10	1/2[Pd2(dba)3·CHCl3] + 4(t-Oct)NC	70	29
11	1/2[Pd2(dba)3·CHCl3] + 4P(o-Tol)3	0	quant.
12	1/2[Pd2(dba)3·CHCl3] + 2dppe	20	75
13	1/2[Pd2(dba)3·CHCl3] + dppf	0	94
14	1/2[Pd2(dba)3·CHCl3] + 2bpy	19	77

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Fig. 1

Having identified optimal catalyst, Pd(PPh₃)₄, a series of nucleophiles were applied to the reaction of 1a and the results are summarized in Table 2.

Table 2 The palladium-catalyzed allylic substitution reaction of α-trifluoromethylated allylic mesylates with various carbon nucleophiles

Entry	Nucleophile (Nu-Metal)	Temp./°C	Product	Yield of 3 (%)^a	Unreacted 1a (%)^a
a Determined by ^19F NMR. Values in parentheses are of isolated yields.b An unidentified product was produced in 76% yield.c A diene was formed in 80% yield.
1		rt	3a-E	(99)	0
2		rt	3b-E	(98)	0
3		rt	3c-E	(86)	trace
4		rt	3d-E	(99)	0
5		rt	3e-E	(94)	0
6		rt	—	0	84
7		50	—	0^b	13
8		rt	—	0	96
9		50	—	0	79
10	PhZnCl	rt	—	0	98
11	PhZnCl	50	—	0	80
12	LiCH2NO2	rt	—	0^c	0

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As shown in entries 1–5, the carbanions derived from diethyl malonate, ethyl acetoacetate, malononitrile, ethyl cyanoacetate, and Hornor–Wadsworth–Emmons reagent reacted smoothly with allyl mesylate 1a in the presence of Pd(PPh₃)₄ to give the corresponding 3a-E in almost quantitative yields. In all cases, the γ-products with E configuration at the newly created olefinic bond were formed exclusively. No trace of the α-products were detected at all. In entries 2, 4, and 5, the mixture of diastereomers was produced in a ratio of ca. 1 : 1.

We also examined the reaction of allyl mesylate 1a with other carbon nucleophiles such as silyl enol ether, zinc acetylide, phenyl zinc reagent, and lithionitromethane, in the presence of the palladium catalyst at room temperature or 50 °C (entries 6–12). However, the desired products were not formed and the starting material was recovered in almost all cases. In the reaction with lithionitromethane, the decomposition of the π-allylpalladium complex occurred preferentially to lead to the diene 5a in 80% yield (entry 12 and Scheme 3).

Scheme 3

We next investigated the effect of the side chain R in the allylic mesylate 1 on the present reaction as compiled in Table 3. The substrate 1b having a phenyl group as R was too unstable to isolate, so that the crude material after the mesylation of the corresponding allylic alcohol was employed for the reaction. In this case, a slight decrease in the stereoselectivity at the newly created olefinic bond was observed (entry 2). Changing the substituent from the phenyl to benzyloxymethyl group led to a further decrease in the stereoselectivity at the double bond (entry 3).

Table 3 Examination of the effect of the side chain R

Entry	R	Product	Yield of 3 (%)^a	E : Z^b
a Isolated yield.b Determined by ^19F NMR.c Based on the corresponding allylic alcohol.
1	n-C6H13 (a)	3a-E	99	100 : 0
2	Ph (b)	3f-E, Z	81^c	94 : 6
3	CH2OBn (c)	3g-E, Z	81	72 :28

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Interestingly, in the reaction of 1d where R was H, the bisallylated products 6-EE, 6-EZ, and 6-ZZ were obtained randomly, in addition to the monoallylated products 3h-E and 3h-Z (Table 4, entry 1). In order to obtain the allylic substitution products stereoselectively, we re-examined the effect of transition metal catalysts, as summarized in Table 4.

Table 4 The reaction of α-trifluoromethylated allyl mesylate with sodiomalonate in the presence of palladium or molybdenum catalyst

Entry	Catalyst	Yield of 3 and 6 (%)^a	3 (E : Z) : 6 (EE : EZ : ZZ)^a	Unreacted 1d (%)^a
a Determined by ^19F NMR and GC.b bpy: 2,2′-bipyridyl, 7.c IP(Ph): iminophosphine, 8. IP(Cy): iminophosphine, 9.d Stirred for 24 h.e DME was used as a solvent.f 1,4-Dioxane was used as a solvent.g phen : 1,10-phenanthroline, 10.h DI : diimine, 11.i BPA : bis-picolinylamide, 12.
1	Pd(PPh3)4	95	56 (60 : 40) : 44 (43 : 45 : 12)	0
2	1/2[Pd2(dba)3·CHCl3]	64	39 (100 : 0) : 61 (95 : 5 : 0)	33
3	1/2[Pd2(dba)3·CHCl3] + 4(o-Tol)3P	68	57 (90 : 10) : 43 (90 : 10 : 0)	28
4	1/2[Pd2(dba)3·CHCl3] + 2dppe	85	56 (100 : 0) : 44 (95 : 5 : 0)	13
5	1/2[Pd2(dba)3·CHCl3] + 2bpy^b	85	56 (100 : 0) : 44 (97 : 3 : 0)	5
6	1/2[Pd2(dba)3·CHCl3] + 2IP(Ph)^c	95	52 (100 : 0) : 48 (62 : 34 : 4)	0
7	Mo(CO)3(C7H8)	0	—	88
8	Mo(CO)3(C7H8) + 2PPh3	0	—	96
9	Mo(CO)3(C7H8) + dppe	71	86 (57 : 43) : 14 (50 : 40 : 10)	24
10	Mo(CO)3(C7H8) + IP(Ph)^c	22	96 (77 : 23) : 4 (100 : 0 : 0)	67
11	Mo(CO)3(C7H8) + IP(Cy)^c	18	100 (67 : 33) : 0	72
12	Mo(CO)3(C7H8) + bpy	29	93 (100 : 0) : 7 (100 : 0 : 0)	66
13^d	Mo(CO)3(C7H8) + bpy	42	90 (100 : 0) : 10 (100 : 0 : 0)	58
14^e	Mo(CO)3(C7H8) + bpy	41	91 (100 : 0) : 9 (100 : 0 : 0)	53
15^f	Mo(CO)3(C7H8) + bpy	92	77 (100 : 0) : 23 (100 : 0 : 0)	4
16^d	Mo(CH3CN)3(C7H8) + bpy	57	84 (100 : 0) : 16 (100 : 0 : 0)	34
17	Mo(CO)3(C7H8) + phen^g	51	88 (100 : 0) : 12 (100 : 0 : 0)	49
18	Mo(CO)3(C7H8) + phen^g	54	87 (100 : 0) : 13 (100 : 0 : 0)	37
19	Mo(CO)3(C7H8) + DI^h	0	—	80
20	Mo(CO)3(C7H8) + BPA^i	0	—	quant.

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Palladium catalysts were employed bearing a variety of ligands such as (o-Tol)₃P, dppe, 2,2′-bipyridyl 7, and iminophosphine 8 (shown in Fig. 2). As shown in entries 2–6, the allylic substitution reaction of 1d with 2a proceeded smoothly to give the corresponding products 3 and 6 in good to excellent yields. In all cases, the γ-product was obtained exclusively and no trace of the α-product was detected. However, the monoallylated- and bisallylated products were obtained in almost 1 : 1 ratio and high E selectivity was obtained at the newly formed olefinic bond.

Fig. 2

In search for more efficient catalysts affording high levels of regio- and stereo-selectivity, we tried using molybdenum catalysts for the allylic substitution reaction of 1d. As shown in entry 7, molybdenum(cycroheptatriene)tricarbonyl did not give the desired product at all. Even when triphenylphosphine was employed as the ligand, in sharp contrast to the palladium catalyst, the product was not formed (entry 8). The use of dppe and iminophosphines (IP(Ph) 8 and IP(Cy) 9) led to the preferential formation of 3, but the stereoselectivity in 3 or the yield was greatly decreased (entries 9–11).

The use of bipyridyl ligand, on the other hand, gave exclusive E-stereoselection at the newly formed olefinic bond as shown in entry 12, although the yield was only 29%. Prolonged reaction time increased the yield from 29 to 42% (entry 13). The reaction in DME did not afford a dramatic change in the yield (entry 14). Of much interest is that the employment of 1,4-dioxane as the solvent improved the reaction markedly, giving a high yield (92%) as well as the high regio- and stereo-selectivity (3 : 6 = 77 : 23, the exclusive E selectivity, entry 15). Phenanthroline 10 was also a good ligand, which afforded high regio- and stereo-selectivity, although the reaction was slightly slow (entries 17 and 18). It was also found that neither diimine 11 nor bispicolinylamide 12 gave the allylated product (entries 19 and 20). In all cases, only γ-products were obtained and no trace of the α-products was detected.

Mechanism

The following mechanism might be proposed, as described in Schemes 4 and 5.

Scheme 4

Scheme 5

Generally, palladium-catalyzed allylic substitution reaction with stabilized carbon nucleophiles occurs via anti oxidative addition-anti nucleophilic attack mode, providing the allylated products with overall retention of configuration (Scheme 4, Path A).¹² The molybdenum-catalyzed reaction has also been known to proceed with overall retention of configuration.¹³ However it has been recently reported that the mode of action of molybdenum catalyst may differ from that of palladium (Path B). Thus, the molybdenum-catalyzed reaction is suggested to take place via syn oxidative addition-syn nucleophilic attack mode.¹⁴ Based on this proposed mechanism, the molybdenum complex could coordinate with the allylic mesylate leaving group and an olefin, providing the oxidative product Int-B with the retention of configuration. The nucleophile attacks on the same face as that occupied by Mo, resulting in a net retention in this pathway.

In Int-A or Int-B, the transition metal might be closer to a CF₃ group than the R group due to the electron-withdrawing effect of the CF₃ group.¹⁵ Therefore, the nucleophile reacts preferentially at the less hindered γ-carbon to give the γ-product 3.

In the reaction of 1d (R = H) with sodiomalonate, it is highly possible that sodiomalonate abstracts α-proton of γ-product 3, forming the α-allylated sodiomalonate 13 (Scheme 5). The newly formed nucleophile 13 attacks the γ-carbon of Int-A or Int-B. In this case, Int-A may react more smoothly than Int-B does because of the large steric repulsion between molybdenum species and the bulky nucleophile 13. As a result, higher selectivity of 3/6 was observed in the molybdenum-catalyzed reaction than in the palladium reaction.

For the molybdenum-catalyzed allylic substitution reaction, it has been also reported thus far that the reaction with stabilized carbon nucleophiles proceeds via anti oxidative addition-anti nucleophilic attack mode, like the palladium-catalyzed reaction.¹⁶ Therefore, the detailed reaction mechanism for the present study remains unclear at present and an exact explanation for the mechanism awaits further investigation.

Conclusions

In summary, we have investigated the transition metal-catalyzed allylic substitution reaction of α-trifluoromethylated allyl mesylate with various carbon nucleophiles in detail. Only stabilized carbanions such as sodiomalonate, ethyl sodiocyanoacetate, etc. reacted with the mesylate smoothly to give the corresponding alkylation products in excellent yields. It was found that the side chain R in the mesylates affected the reaction significantly. Thus, the monoallylated product was obtained in high yields via palladium-catalyzed reaction in the case of R = n-C₆H₁₃, Ph etc., however, the use of 1d (R = H) led to the formation of bisallylated product along with the monoallylated one. The best yield and the best stereoselectivity were obtained when the molybdenum catalyst with a 2,2′-bipyridyl ligand was employed.

Experimental

General methods

Infrared spectra (IR) were taken on a Shimadzu FTIR-8200(PC) spectrometer as film on a NaCl plate. ¹H and ¹³C NMR spectra were measured with a Bruker DRX-500 NMR spectrometer in a chloroform-d (CDCl₃) solution with tetramethylsilane (Me₄Si) as an internal reference. A JEOL JNM-EX90A (84.21 MHz) FT-NMR spectrometer was used for determining ¹⁹F NMR spectra in a CDCl₃ solution with trichlorofluoromethane as internal standard. High-resolution mass spectra (HRMS) were taken on a Hitachi M-80B mass spectrometer by electron impact (EI), chemical ionization (CI), and fast atom bombardment (FAB) methods. Thin-layer chromatography (TLC) was done on aluminium sheets coated with silica gel (Merck 60 F₂₅₄), and column chromatography was carried out using silica gel (Wacogel C-200) as adsorbent.

Preparation of substrate 1d

To a THF solution of trifluoroacetaldehyde, prepared readily from trifluoroacetaldehyde monohydrate (40 mmol) and conc. H₂SO₄ (40 mmol), was added a THF solution of vinylmagnesium bromide (20 mmol) at −78 °C. The reaction mixture was stirred for several hours at that temperature, and the reaction was quenched with sat. NH₄Cl aq.. The mixture was extracted with ether three times, and the combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, and filtered. The filtrate was gradually concentrated to remove solvents (THF and ether) to the yellow residue which was used without further purification.

To a CH₂Cl₂ solution of trifluoromethylated allylic alcohol (1 mmol) was added methanesulfonyl chloride (1.2 mmol) and Et₃N (1.2 mmol) at 0 °C. The whole was stirred for several hours at that temperature. After quenching the reaction with sat. NH₄Cl, the whole was extracted with CH₂Cl₂ three times, and the combined organic layers were dried over anhydrous Na₂SO₄, concentrated in vacuo. The residue was purified by silica gel column chromatography to give the corresponding allyl mesylate 1d (∼41% yield).

1-(Trifluoromethyl)-2-propenyl methanesulfonate (1d)

¹H NMR (CDCl₃) δ 3.11 (3H, s), 5.29 (1H, dq, J = 6.5 Hz, 6.5 Hz), 5.67 (1H, d, J = 10.5 Hz), 5.72 (1H, d, J = 17.2 Hz), 5.91 (1H, ddd, J = 6.5 Hz, 10.5 Hz, 17.2 Hz); ¹⁹F NMR (CDCl₃) δ − 77.22 (3F, d, J = 6.5 Hz); ¹³C NMR (CDCl₃) δ 39.4, 77.1 (q, J = 34.4 Hz), 122.1 (q, J = 280.9 Hz), 125.3, 126.1; IR (neat) ν 725 (m), 764 (m), 843 (s), 870 (m), 949 (s), 1011 (s), 1109 (m), 1132 (s), 1182 (s), 1271 (s), 1337 (s), 1371 (s), 1418 (m), 2947 (w), 3038 (w); HRMS (CI) m/z 205.0146, found 205.0139 (M + H), calcd for C₅H₈F₃O₃³²S.

Typical procedure for the reaction of allyl mesylate 1a with sodiomalonate

To a solution of Pd(PPh₃)₄ (19 mg, 5 mol%, 0.02 mmol) in THF (3 mL) was added allyl mesylate 1a (93 mg, 0.34 mmol) at 0 °C. After stirring of the reaction mixture for 10 min, sodiomalonate, 2a, prepared from diethyl malonate (1.2 eq. 0.41 mmol) and NaH (1.2 eq. 0.41 mmol), was added to the reaction mixture, followed by warming of the solution to room temperature, then stirred for 2 h. The reaction was quenched with water, and the whole was extracted with ethyl acetate three times. The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, and concentrated in vacuo. The residue was purified by silica gel column chromatography to give the corresponding allylated product 3a-E (119 mg, 99% yield).

Diethyl 1-(3,3,3-trifluoro-(1E)-propenyl)heptylmalonate (3a-E)

¹H NMR (CDCl₃) δ 0.87 (3H, t, J = 7.0 Hz), 1.23–1.43 (16H, m), 2.87 (1H, ddt, J = 3.5 Hz, 9.0 Hz, 9.0 Hz), 3.36 (1H, d, J = 9.0 Hz), 4.16 (2H, d, J = 7.5 Hz), 4.20 (2H, d, J = 7.5 Hz), 5.68 (1H, dq, J = 6.5 Hz, 15.5 Hz), 6.27 (1H, ddq, J = 2.0 Hz, 9.0 Hz, 15.5 Hz); ¹⁹F NMR (CDCl₃) δ −64.74 (3F, d, J = 6.5 Hz); ¹³C NMR (CDCl₃) δ 13.9, 14.0, 22.5, 26.8, 28.9, 31.5, 31.9, 41.8, 56.0, 61.5, 61.6, 120.8 (q, J = 33.5 Hz), 122.6 (q, J = 269.2 Hz), 140.0 (q, J = 6.5 Hz), 167.6, 167.7; IR (neat) ν 671 (m), 795 (s), 856 (m), 979 (m), 1033 (m), 1126 (s), 1280 (s), 1369 (m), 1465 (m), 1681 (m), 1735 (s), 2858 (m), 2931 (s); HRMS (CI) m/z 353.1940, found 353.1938 (M + H), calcd for C₁₇H₂₈F₃O₄.

1-(3,3,3-Trifluoro-(1E)-propenyl)heptylmalononitrile (3c-E)

¹H NMR (CDCl₃) δ 0.89 (3H, t, J = 7.0 Hz), 1.26–1.35 (8H, m), 1.66–1.69 (1H, m), 1.76–1.78 (1H, m), 2.77 (1H, ddt, J = 5.5 Hz, 9.5 Hz, 9.5 Hz), 3.79 (1H, d, J = 5.5 Hz), 5.96 (1H, dq, J = 6.0 Hz, 16.0 Hz), 6.24 (1H, ddq J = 1.5 Hz, 9.5 Hz, 16.0 Hz); ¹⁹F NMR (CDCl₃) δ −65.23 (3F, d, J = 6.0 Hz); ¹³C NMR (CDCl₃) δ 13.9, 22.4, 26.5, 27.8, 28.7, 31.4, 43.0, 110.7, 110.9, 121.8 (q, J = 270.1 Hz), 124.7 (q, J = 34.8 Hz), 135.3 (q, J = 6.2 Hz); IR (neat) ν 864 (w), 976 (m), 1130 (s), 1211 (w), 1277 (m), 1315 (m), 1366 (w), 1466 (w), 1686 (w), 2862 (m), 2932 (s); HRMS (CI) m/z 259.1422, found 259.1421 (M + H), calcd for C₁₃H₁₈F₃N₂.

Ethyl 1-(3,3,3-trifluoro-(1E)-propenyl)heptylcyanoacetate (diastereomeric ratio = 60 : 40) (3d-E)

¹H NMR (CDCl₃) δ 0.87–0.90 (3H, m), 1.29–1.38 (13H, m), 2.83–2.89 (1H, m), 3.50 (1H, d, J = 6.3 Hz) (isomer), 3.64 (1H, d, J = 4.5 Hz) (another isomer), 4.23–4.27 (2H, m), 5.75–5.83 (1H, m), 6.22 (1H, ddq, J = 2.0 Hz, 9.6 Hz, 15.6 Hz) (isomer), 6.27 (1H, ddq, J = 2.0 Hz, 9.7 Hz, 15.6 Hz) (another isomer); ¹⁹F NMR (CDCl₃) δ −64.65 (3F, d, J = 6.6 Hz) (isomer), −64.73 (3F, d, J = 6.6 Hz) (another isomer); ¹³C NMR (CDCl₃) δ 13.9, 22.5, 26.6, 26.7, 28.7, 28.8, 28.8, 31.0, 31.5, 32.1, 42.3, 42.3, 43.3, 42.4, 63.1, 114.2, 120.3 (q, J = 38.3 Hz) (isomer), 120.5 (q, J = 269.3 Hz) (isomer), 122.7 (q, J = 269.9 Hz) (another isomer), 137.3 (q, J = 6.4 Hz) (isomer), 138.1 (q, J = 6.0 Hz) (another isomer), 164.6, 164.74; IR (neat) ν 856 (w), 980 (m), 1026 (m), 1126 (s), 1277 (m), 1369 (m), 1466 (m), 1682 (m), 1747 (s), 2341 (m), 2862 (m), 2932 (s); HRMS (CI) m/z 306.1681, found 306.1685 (M + H), calcd for C₁₅H₂₃F₃NO₂.

Ethyl 1-(3,3,3-trifluoro-(1E)-propenyl)heptyldiethylphosphonoacetate (diastereomeric ratio = 56 : 44) (3e-E)

¹H NMR (CDCl₃) δ 0.85–0.88 (3H, m), 1.20–1.47 (19H, m), 2.78–2.89 (1H, m), 2.96 (1H, dd, J = 9.8 Hz, 20.3 Hz) (isomer), 3.04 (1H, dd, J = 7.5 Hz, 21.5 Hz) (another isomer), 4.06–4.19 (4H, m), 4.23 (2H, q, J = 7.0 Hz) (isomer), 5.68 (1H, dq, J = 6.5 Hz, 15.5 Hz) (another isomer), 5.72 (1H, dq, J = 6.5 Hz, 15.5 Hz) (isomer), 6.17 (1H, ddq, J = 2.0 Hz, 10.0 Hz, 15.5 Hz) (isomer), 6.36 (1H, ddq, J = 2.0 Hz, 10.0 Hz, 15.5 Hz) (another isomer); ¹⁹F NMR (CDCl₃) δ −64.66 (3F, d, J = 6.5 Hz); ¹³C NMR (CDCl₃) δ 13.9, 14.0, 14.1, 16.1–16.3 (m), 22.47, 22.48, 26.4, 26.7, 28.8, 31.5, 31.5, 32.31, 32.37, 41.0 (d, J = 3.4 Hz) (isomer), 41.1 (d, J = 4.1 Hz) (another isomer), 49.7 (d, J = 139.9 Hz) (isomer), 50.7 (d, J = 133.9 Hz) (another isomer), 61.4, 61.6, 62.5 (d J = 7.1 Hz) (isomer), 62.7 (d J = 7.4 Hz) (another isomer), 120.3 (q, J = 33.5 Hz) (isomer), 120.4 (q, J = 33.3 Hz) (another isomer), 122.7 (q, J = 269.2 Hz) (isomer), 140.2–140.5 (m), 167.8 (q, J = 3.9 Hz), 168.2 (q, J = 3.3 Hz); IR (neat) ν 675 (w), 795 (w), 860 (w), 972 (m), 1026 (s), 1123 (s), 1258 (s), 1369 (m), 1466 (m), 1682 (m), 1736 (s), 2858 (m), 2932 (w); HRMS (CI) m/z 417.2018, found 417.2022 (M + H), calcd for C₁₈H₃₃F₃₀O₅P.

Ethyl 1-(3,3,3-trifluoro-(1E)-propenyl)heptylacetoacetate (diastereomeric ratio = 58 : 42) (3b-E)

¹H NMR (CDCl₃) δ 0.86 (3H, t, J = 7.0 Hz), 1.22–1.45 (13H, m), 2.17 (3H, s) (isomer), 2.23 (3H, s) (another isomer), 2.90–2.92 (1H, m), 3.46 (1H, d, J = 9.0 Hz) (isomer), 3.50 (1H, d, J = 9.0 Hz) (another isomer), 4.14 (2H, q, J = 7.0 Hz) (isomer), 4.20 (2H, d, J = 7.0 Hz) (another isomer), 5.66 (1H, dq, J = 6.5 Hz, 16.0 Hz) (isomer), 5.67 (1H, dq, J = 6.5 Hz, 16.0 Hz) (another isomer), 6.14–6.21 (1H, m); ¹⁹F NMR (CDCl₃) δ −64.72 (3F, d, J = 6.5 Hz); ¹³C NMR (CDCl₃) δ 13.95, 14.02, 22.5, 26.8, 26.9, 28.9, 29.6, 30.0, 31.5, 31.6, 32.0, 41.3, 61.6, 61.7, 63.6, 63.8, 120.9 (q, J = 33.6 Hz) (isomer), 121.0 (q, J = 33.6 Hz), 122.5 (q, J = 269.5 Hz) (isomer), 122.6 (q, J = 269.5 Hz) (another isomer), 139.9 (q, J = 6.8 Hz) (isomer), 140.1 (q, J = 6.6 Hz) (another isomer), 167.9, 168.0, 201.1, 201.2; IR (neat) ν 679 (w), 810 (w), 856 (w), 980 (m), 1026 (m), 1126 (s), 1277 (s), 1362 (s), 1466 (m), 1632 (w), 1682 (m), 1720 (s), 2858 (m), 2932 (s); HRMS (EI) m/z 323.1834, found 323.18434 (M + H), calcd for C₁₆H₂₆F₃O₃.

Diethyl 1-benzyloxymethyl-4,4,4-trifluoro-(2E)-butenyl malonate (3f-E)

¹H NMR (CDCl₃) δ 1.23 (6H, t, J = 7.0 Hz), 3.18–3.23 (1H, m), 3.53–3.64 (2H, m), 3.72 (1H, d, J = 8.0 Hz), 4.10–4.23 (4H, m), 4.45–4.83 (2H, m), 5.67–5.78 (1H, m), 6.47 (1H, ddq, J = 2.0 Hz, 9.5 Hz, 16.0 Hz), 7.28–7.30 (3H, m), 7.33–7.36 (2H, m); ¹⁹F NMR (CDCl₃) δ −64.95 (3F, d, J = 6.6 Hz); ¹³C NMR (CDCl₃) δ 13.96, 13.97, 41.7, 52.4, 61.6, 61.7, 69.8, 73.2, 121.3 (q, J = 269.2 Hz), 127.6, 127.8, 128.4, 137.5 (q J = 6.5 Hz), 137.7, 167.68, 167.72; IR (neat) ν 700 (m), 739 (m), 864 (w), 978 (m), 1030 (s), 1121 (s), 1369 (s), 1454 (m), 1680 (m), 1732 (s), 2870 (m), 2986 (m); HRMS (FAB) m/z 389.1576, found 389.1580 (M + H), calcd for C₁₉H₂₄F₃O₅.

Diethyl 1-benzyloxymethyl-4,4,4-trifluoro-(2Z)-butenyl malonate (3f-Z)

¹H NMR (CDCl₃) δ 1.23 (3H, t, J = 7.0 Hz), 3.18–3.23 (1H, m), 3.53–3.64 (2H, m), 3.76 (1H, d, J = 8.0 Hz), 4.10–4.23 (4H, m), 4.45–4.83 (2H, m), 5.67–5.78 (1H, m), 6.23 (1H, dd, J = 11.5 Hz, 11.5 Hz), 7.28–7.30 (3H, m), 7.33–7.36 (2H, m); ¹⁹F NMR (CDCl₃) δ −58.69 (3F, d, J = 7.8 Hz); ¹³C NMR (CDCl₃) δ 13.97, 14.03, 38.6, 52.2, 61.51, 61.53, 70.4, 73.1, 120.5 (q, J = 33.8 Hz), 122.6 (q, J = 269.2 Hz), 127.6, 127.7, 128.3, 137.8, 139.4 (q J = 6.5 Hz), 167.68, 167.72.

Diethyl 4,4,4-trifluoro-1-phenyl-(2E)-butenyl malonate (3g-E)

¹H NMR (CDCl₃) δ 1.00 (3H, t, J = 7.0 Hz), 1.27 (3H, t, J = 7.0 Hz), 3.84 (1H, d, J = 10.5 Hz), 3.97 (2H, dq, J = 2.5 Hz, 7.0 Hz), 4.18–4.24 (3H, m), 5.65 (1H, dq, J = 6.5 Hz, 15.6 Hz), 6.56 (1H, ddq, J = 2.0 Hz, 8.0 Hz, 15.6 Hz), 7.21–7.23 (1H, m), 7.25–7.28 (1H, m), 7.32–7.34 (2H, m); ¹⁹F NMR (CDCl₃) δ −64.78 (3F, d, J = 6.5 Hz); ¹³C NMR (CDCl₃) δ 13.7, 14.0, 47.3, 56.8, 61.6, 61.9, 120.2 (q, J = 33.8 Hz), 122.6 (q, J = 269.8 Hz), 127.8, 128.1, 128.9, 137.8, 139.4 (q, J = 6.5 Hz), 166.8, 167.3; IR (neat) ν 559 (m), 608 (w), 673 (w), 700 (s), 766 (m), 862 (m), 978 (m), 1032 (s), 1138 (s), 1454 (m), 1497 (m), 1603 (w), 1678 (m), 1732 (m), 2909 (m), 2986 (s); HRMS (FAB) m/z 345.1314, found 345.1317 (M + H), calcd for C₁₇H₂₀F₃O₄.

Diethyl 4,4,4-trifluoro-(2E)-butenyl malonate (3h-E)

¹H NMR (CDCl₃) δ 1.27 (6H, t, J = 7.0 Hz), 2.73–2.75 (2H, m), 3.46 (1H, t, J = 7.2 Hz), 4.21 (4H, q, J = 7.0 Hz), 5.72 (1H, dq, J = 7.0 Hz, 16.0Hz), 6.35 (1H, dtq, J = 2.0 Hz, 7.0 Hz, 16.0 Hz); ¹⁹F NMR (CDCl₃) δ −64.95 (3F, d, J = 7.0 Hz); ¹³C NMR (CDCl₃) δ 14.0, 30.4, 50.5, 61.7, 121.1 (q, J = 33.5 Hz), 122.5 (q, J = 269.3 Hz), 136.0 (q, J = 6.6 Hz), 168.2; IR (neat) ν 862 (w), 970 (m), 1034 (m), 1096 (m), 1128 (s), 1279 (s), 1371 (m), 1448 (m), 1682 (m), 1736 (s), 2988 (m); HRMS (CI) m/z 269.1001, found 269.1002 (M + H), calcd for C₁₁H₁₆F₃O₄.

Diethyl bis(4,4,4-trifluoro-(2E)-butenyl)malonate (6-EE)

¹H NMR (CDCl₃) δ 1.26 (6H, t, J = 7.3 Hz), 2.43 (4H, d, J = 7.5 Hz), 4.22 (4H, q, J = 7.3 Hz), 5.70 (2H, dq, J = 6.5 Hz, 15.8 Hz), 6.28 (2H, dtq, J = 2.0 Hz, 7.5 Hz, 15.5 Hz); ¹⁹F NMR (CDCl₃) δ −65.07 (6F, d, J = 6.5 Hz); ¹³C NMR (CDCl₃) δ 13.9, 35.6, 56.4, 62.0, 122.3 (q, J = 269.5 Hz), 122.6 (q, J = 33.7 Hz), 134.3 (q, J = 6.5 Hz), 169.5; IR (neat) ν 681 (w), 856 (w), 974 (m), 1032 (m), 1124 (s), 1205 (s), 1275 (s), 1350 (m), 1447 (m), 1682 (m), 1732 (s), 2988 (s); HRMS (FAB) m/z 377.1188, found 377.1182 (M + H), calcd for C₁₅H₁₉F₆O₄.

References

1. For a review on catalytic allylic substitutions, see: (a) J. Tsuji, Palladium Reagents and Catalysts, John Wiley, Chichester, 1995; (b) B. M. Trost and D. L. Van Vranken, Chem. Rev., 1996, 96, 395–422; (c) T. Hachiya, in Catalytic Asymmetric Synthesis, ed. I. Ojima, VCH, New York, 1993, p. 325; (d) C. G. Frost, J. Howarth and J. M. Williams, Tetrahedron: Asymmetry, 1992, 3, 1089–1122; (e) G. Consiglio and M. Waymouth, Chem. Rev., 1989, 89, 257–276.
2. (a) T. Hayashi, M. Kawatsura and Y. Uozumi, J. Am. Chem. Soc., 1998, 120, 1681–1687; (b) M. Nakoji, T. Kanayama, T. Okino and Y. Takemoto, J. Org. Chem., 2002, 67, 7418–7423; (c) T. Hayashi, M. Kawatsura and Y. Uozumi, Chem. Commun., 1997, 561–562; (d) U. Kazmaier and F. L. Zumpe, Angew. Chem., Int. Ed., 1999, 38, 1468–1470.
3. (a) B. M. Trost, S. Hildbrand and K. Dogra, J. Am. Chem. Soc., 1999, 121, 10416–10417; (b) B. M. Trost, K. Dogra, I. Hachiya, T. Emura, D. L. Hughes, S. Krska, R. A. Reamer, M. Palucki, N. Yasuda and P. J. Reider, Angew. Chem., Int. Ed., 2002, 41, 1929–1932; (c) F. Glorious, M. Neuburger and A. Pfaltz, Helv. Chim. Acta, 2001, 84, 3178–3196; (d) F. Glorious and A. Pfaltz, Org. Lett., 1999, 1, 141–144.
4. (a) B. M. Trost and M.-H. Hung, J. Am. Chem. Soc., 1983, 105, 7757–7759; (b) R. Prétôt, G. C. Lloyd-Jones and A. Pfaltz, Pure Appl. Chem., 1998, 70, 1035–1040.
5. (a) R. Takeuchi, Synlett, 2002, 1954–1965; (b) R. Takeuchi, N. Ue, K. Tanabe, K. Yamashita and N. Shiga, J. Am. Chem. Soc, 2001, 123, 9525–9534; (c) T. Ohmura and J. F. Hartwig, J. Am. Chem. Soc., 2002, 124, 15164–15165; (d) B. Bartels and G. Helmchen, Chem. Commun., 1999, 741–742.
6. (a) P. A. Evans and J. E. Robinson, Org. Lett., 1999, 1, 1929–1931; (b) P. A. Evans and L. K. Kennedy, Org. Lett., 2000, 2, 2213–2215; (c) P. A. Evans and L. J. Kennedy, J. Am. Chem. Soc., 2001, 123, 1234–1235; (d) T. Hayashi, A. Okada, T. Suzuki and M. Kawatsura, Org. Lett., 2003, 5, 1713–1715; (e) P. A. Evans and D. K. Leahy, J. Am. Chem. Soc., 2002, 124, 7882–7883.
7. (a) T. Kondo, H. Ono, N. Satake, T. Mitsudo and Y. Watanabe, Organometallics, 1985, 14, 1945–1953.
8. (a) Y. Hanzawa, S. Ishizawa and Y. Kobayashi, Chem. Pharm. Bull., 1988, 36, 4209–4212; (b) Y. Hanzawa, S. Ishizuka, H. Ito, Y. Kobayashi and T. Taguchi, J. Chem. Soc., Chem. Commun., 1990, 394–395; (c) T. Okano, H. Matsubara, T. Kusukawa and M. Fujita, J. Organomet. Chem., 2003, 676, 43–48.
9. (a) T. Konno, K. Nagata, T. Ishihara and H. Yamanaka, J. Org. Chem., 2002, 67, 1768–1775; (b) T. Konno, T. Ishihara and H. Yamanaka, Tetrahedron Lett., 2000, 41, 8467–8472.
10. The palladium-catalyzed allylic substitution reactions of fluorine-containing allylic acetate, carbonate, phosphonate, and tosylate have been reported previously. See ref. 8.
11. The same high regio- and stereo-selectivity have been reported previously. See ref 8.
12. (a) B. M. Trost, Acc. Chem. Res., 1980, 13, 385–393; (b) See ref. 1b.
13. (a) B. M. Trost and M. Lautens, J. Am. Chem. Soc., 1982, 104, 5543–5545; (b) B. M. Trost and M. Lautens, J. Am. Chem. Soc., 1987, 109, 1469–1478; (c) B. M. Trost and C. A. Merlic, J. Am. Chem. Soc., 1990, 112, 9590–9600.
14. (a) A. V. Malkov, I. R. Baxendale, D. J. Mansfield and P. Kocovsky, J. Chem. Soc., Perkin Trans. 1, 2001, 1234–1240; (b) D. Dvorak, I. Stary and P. Kocovsky, J. Am. Chem. Soc., 1995, 117, 6130–6131; (c) Y. D. Ward, L. A. Villanueva, G. D. Allred and L. S. Liebeskind, J. Am. Chem. Soc., 1996, 118, 897–898; (d) A. Rubio and L. S. Liebeskind, J. Am. Chem. Soc., 1993, 115, 891–901.
15. It has been reported that the palladium atom in the η³ intermediate lies closer to the carbon attached to the electron-withdrawing group. See (a) E. Keinan and M. Pereta, J. Org. Chem., 1983, 48, 5302–5309; (b) E. Keinan and Z. Roth, J. Org. Chem., 1983, 48, 1769–1772.
16. (a) B. M. Trost and M. Lautens, Tetrahedron, 1987, 43, 4817–4840; (b) D. L. Hughes, M. Palucki, N. Yasuda, R. A. Reamer and P. J. Reider, J. Org. Chem., 2002, 67, 2762–2768; (c) see ref. 3a.

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