CsF in organic synthesis. Inversion of secondary mesylates and tosylates

Tetrahedron, Vol. 53, No. 40, pp. 13633-13640, 1997

© 1997 ElsevierScienceLtd All fights reserved. Printedin Great Britain 0040..4020/97 $17.00 + 0.00

Pergamon PII: S0040-4020(97)00900-9

CsF in Organic Synthesis. Inversion of Secondary Mesylates and Tosylates Junzo Otera,* Koichi Nakazawa, Koichi Sekoguchi and Akihiro Orita Department of Applied Chemistry, Okayama University of Science, Ridai-cho, Okayama 700, Japan

Abstract: Clean inversion of secondary mesylates and tosylates is effected by CsF in DMF. A variety of oxygen-,

sulfur-, nitrogen-, and carbon-nucleophiles are employable. The reaction conditions have been optimized. The use of CsF in DMF is crucial and the reaction proceeds on the surface of solid CsF. It is suggested that hydrogen bonding between CsF and an active hydrogen of nucleophiles is responsible for the smooth reaction. Cesium carbonate fails to give rise to high specificity of inversion indicative of superiority of CsF. © 1997 Elsevier Science Ltd.

INTRODUCTION

The SN2 reaction of secondary alcohol derivatives is one of the most important manipulations to arrive at optically active compounds. While Mitsunobu reaction enables direct inversion of the alcohols, ~) use of the substrates substituted by a labile nucleofuge is more general.

Although triflates, 2~ xanthates, 3) and

(alkoxymethylene)dimethylammonium chlorides 4) were found to be effective, mesylates and tosylates have been the oldest but still most frequently employed substrates.

The classical method in which the sulfonates are

exposed to an alkali metal salt of heteroatom nucleophiles suffers from synthetic limitations due to its harsh reaction conditions.

As a result, many modifications have been pursued.

Potassium superoxide convened

mesylates to the inverted alcohol 5) whereas inversion of tosylates was effected by tetrabutylammonium nitrite6) and potassium nitrate. 7)

Recently, cesium carboxylates have received much attention.

Several cesium

carboxylates derived from acetic, propionic, benzoic and amino acids provided the corresponding secondary carboxylates, s) Later, it was reported that use of 18-crown-6 improved the cesium acetate protocol. 9) This method was further applied to triflates '°) and chloromethanesulfonates.' ~ Cesium thiocarboxylates were also employed to obtain optically active thiols.~2) In our studies on CsF in organic synthesis, we disclosed that CsF effected SN2 reaction of secondary mesylates with complete inversion. Remarkably, a variety of heteroatom '3) as well as carbon ~4) nucleophiles are employable in this protocol in contrast to the narrow scope of the precedent methods in which the nucleophiles are limited by the cesium salts that can be employed. Another notable feature of the CsF method is the mildness of the reaction conditions that allow both acid- and base-sensitive functional groups to remain intact.

Due to

such great synthetic promise, we were intrigued to investigate its characteristic features in more detail. Herein are described the optimization of reaction conditions and the scope and limitations of the CsF method. Comparison with reaction with cesium carbonate is also reported. 13633

J. OTERA et al.

13634

RESULTS AND DISCUSSION We have already disclosed that various types of the substrates were employable in our method t3'~4) and, accordingly, only four mesylates derived from (S)-ethyl lactate, (S)-2-octanol, and trans- or cis-4-tert-butyl-1(mesyloxy)cyclohexane, are the substrates of our choice in this study (eq. 1). Despite the synthetic advantages mentioned already, we required excess amounts of CsF and nucleophiles (5 equivalents each) in the reaction with heteroatom nucleophiles. TM Thus, it is of prime significance to scrutinize if the amounts of these two components can be reduced. Table 1 summarizes the results which reveal that no virtual changes occur by use of 3 equivalents of them or even by the one equivalent amount under the appropriate reaction conditions. In general, the use of each one equivalent of 2 and CsF decreases the yields only slightly but the less than one equivalent of CsF results in a sharp decrease in yields. When (S)-la was treated with thiophenol 2b in the presence of 3 equivalents of CsF, racemization occurred (entries 3 and 4). This, however, was suppressed by reducing the amount of CsF to one equivalent (entries 5 and 6). The same held with phthalimide (2d) (entries 9 and 10) and reaction of (S)-lb with benzoic acid (entries 14 and 15). Phenol gives rise to an unsatisfactory %ee (entry 13). In the reaction of trans- and cis-4-tert-butyl-l-(mesyloxy)cyclohexanes ( l c and l d ) with 2b, the products were contaminated by PhSSPh when the excess amount of the nucleophile was used. Accordingly, the substrates were employed in excess (entries 20, 21, 24, and 25). As a whole, reduction of the amount of CsF has proved to be advantageous in terms of improvement of %ee. QSO2Me -= RI~R 2

+

(S)-la R ] = CH3; R 2 = COOEt (S)-lb R 1 = C6Ht3; R 2 = CH 3 lc trans-4-tert-butyl- l-(mesyloxy)cyclohexane

Null or NuTMS

NM

CsF Jim

DMF

R1AR 2 (1)

2a PhCOOH b PhSH c MeCOSH d phthalimide

l d cis-4-tert-butyl-l-(mesyloxy)e TMSN 3 cyclohexane f PhOH Since CsF is poorly soluble in dry DMF (ca. 5 g/100 ml), conceivably, the reaction is promoted by solid CsF.

The following experiments confirmed this supposition. CsF was stirred in DMF for 24 h at room

temperature and the mixture was filtered. To the filtrate was added l a and 2a or 2e and the solution was stirred under the same conditions for reaction (1). The yields of the desired products were only 8 % in both cases. Apparently, the reaction in the homogeneous phase is very slow. This prompts us to conclude that the fluoride anion is not responsible for the promotion of the reaction in consistent with the fact that the reaction conditions are almost neutral) 3'~4) If the fluoride anion is formed, HF should emerges after aqueous workup and, thus, acid-sensitive groups such as THP ethers and acetals cannot survive. Presumably, a special composite matrix is formed between CsF and DMF as the reaction field since this solvent is uniquely superior to other ones. ~5) Strong hydrogen bonding power of alkali metal fluorides has been well elucidated which activates nucleophiles having active hydrogens. ~6) CsF may also serve as a captor of the methanesulfonic acids generated. ~7) Moreover, activation of silyl nucleophiles by CsF is well konwn. Quite naturally, the heterogeneous nature of the reaction gives rise to advantage in the CsF economy. CsF can be recovered readily by filtration after the reaction and reused without appreciable decrease of the yield. Apparently, the requisite use of excess CsF may be partially compensated by the recycling.

CsF in organic synthesis

13635

Table 1. CsF-Promoted Substitution of Secondary Mesylates by Heteroatom Nucleophiles. Reaction

3

.......................................................................

entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

1 (S)-la

(S)-lb

le

1d

2 (equiv) 2a 2a 2b 2b 2b 2b 2e 2e 2d 2d 2e 2e 2f 2b 2b 2e 2d 2e 2e 2b 2b 2e 2e 2b 2b

(3.0) (1.0) (3.0) (1.0) (3.0) (1.3) (3.0) (1.0) (3.0) (2.0) (3.0) (1.2) (3.0) (3.0) (1.3) (3.0) (3.0) (3.0) (1.3) (0.8) (0.8) (3.0) (1.3) (0.8) (0.8)

Equiv of CsF temp (°C) 3.0 1.0 3.0 3.0 1.0 1.0 3.0 1.0 3.0 1.0 3.0 1.0 3.0 3.0 1.0 3.0 3.0 3.0 1.0 1.5 0.8 3.0 1.0 1.5 1.0

50 50 50 50 50 50 40 40 50 50 40 40 50 50 50 40 50 40 40 90 90 90 90 90 90

time (h) 36 36 12 12 12 12 7 7 48 48 12 12 12 3 6 12 24 12 12 5 7 4 7 5 6

yield (%)

%ee or %de

93 79 84 72 85 85 89 76 69 48 89 72 65 83 78 49 60 81 70 90 74 44 32 52 48

99 >9o 1 0 98 99 99 99 2 90 99 99 36 20 >99 >99 >99 >99 >99 >99 >99 >99 >99 >99 >99

3aa 3aa 3ab 3ab 3ab 3ab 3ae 3ac 3ad 3ad 3ae 3ae 3af 3bb 3bb 3be 3bd 3be 3be 3cb 3cb 3ce 3ce 3db 3db

Tosylates are expected to undergo the same reaction as mesylates. This is indeed the case (eq. 2). The results are summarized in Table 2. These substrates are more prone to nucleophilic substitution due to their stronger leaving character. Thus, as given in entry 9, the satisfactory outcome was obtained with phenol that had failed to give a high %ee with mesylate (entry 13, Table 1). Moreover, some reactions proceeded even at room temperature (entries 2, 6, and 9).

OSO2C6H4CH3-P = + RI~R 2 (S)-4a R 1 = CH3; R 2 = COOEt (S)-4b R 1 = C6I--I13; R 2 = CH 3

Nu

CsF 2

~ DMF

A R1

(2) R2

13636

J. OTERA et aL

Table 2. CsF-Promoted Substitution of Secondary Tosylates. Reaction

.

entry

4

1 2 3 4 5 6 7 8 9 10 11

(S)-4a

.

.

.

.

2 (equiv) 2a 2a 2b 2b 2b 2b 2e 2e 2f 2b 2e

(S)-4b .

.

.

.

.

.

.

.

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.

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.

.

Equiv of CsF temp (°C)

(3.0) (3.0) (3.0) (3.0) (2.0) (1.3) (3.0) (3.0) (3.0) (3.0) (3.0) .

.

.

.

.

.

.

3.0 3.0 3.0 1.0 1.0 1.0 3.0 3.0 3.0 3.0 3.0 .

.

.

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.

3

time (h)

50 rt 50 50 50 rt 40 40 rt 60 50 .

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.

12 16 12 12 12 10 7 12 7 3 42 .

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.

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.

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.

.

yield (%)

%ee

99 99 92 72 88 89 81 70 87 86 85

>99 >99 0 94 99 >99 91 >99 >99 0 >99

3aa 3aa 3ab 3ab 3ab 3ab 3ae 3ae 3af 3bb 3be .

.

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.

Previously, we employed 3 equivalents of carbon nucleophiles and CsF in the carbon-carbon bond formation (eq. 3). t4~ Reduction of the amounts of these components has proved to be feasible as shown in Table 3. In the most cases examined, the amounts of nucleophile and/or CsF can be reduced to 1 equivalent except one case (entry 6). It should be noted that no racemization occurred at all except 6ab (91%ee).

Thus,

the classical malonic ester synthesis has been renewed in a stereospecific manner to accommodate various functional groups. In addition, cyanation can be smoothly achieved by use of TMSCN in the presence of 3 equivalent of CsF (entry 7). However, the lesser amount of CsF gave no satisfactory yield (entry 8).

O-SO2Me -=

CsF +

~"

RI~R2 5a b c

(S)-lb R 1 = C6H13; R E = CH 3

I

/

DMF

(S)-la R 1 = CH3; R 2 = COOEt

Nu

I

Null or NuTMS

R1 ~

(3)

R2

CH2(COOEt)2 CHE(CN)COOEt TMSCN

6

Table 3. CsF-Promoted Substitution of Secondary Mesylates by Carbon Nucleophiles. Reaction .

entry 1 2 3 4 5 6 7 8

1 (S)-la

(S)-lb

5 (equiv) 5a 5a 5b 5b 5a 5a 5c 5c

(3.0) (1.3) (3.0) (1.0) (3.0) (3.0) (3.0) (3.0)

Equiv of CsF 3.0 1.0 3.0 1.0 3.0 1.0 3.0 1.0

.

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6 .

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.

temp (°C)

time (h)

45 45 60 45 60 60 50 50

5 5 6 4 7 7 72 72

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yield (%) 6aa 6aa 6ab 6ab 6ba 6ba 6bc 6bc

67 64 59 55 56 7 56 23

.

.

.

.

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.

.

%ee

>99 91 >99 >99

CsF in organic synthesis

13637

As described above, the CsF method has the advantage that a variety nucleophiles are employable while other cesium salt methods require the necessary cesium reagents to be prepared separately.

These cesium

compounds are usually prepared from cesium carbonate. If cesium carbonate itself works as a promoter, then it would be able to substitute CsF. We investigated the feasibility of this process (eq. 4). As shown in Table 4, chemical yields were satisfactory but only poor %ee's were obtained indicative of superiority of CsF.

QSO2Me

Nu

CsCO 3

-

+

Null

~

~COOEt

DMF 2a

(S)-la

b

(4) ~COOEt

3

PhCOOH PhSH

c MeCOSH Table 4. Cs2CO3-Promoted Substitution of Mesylate of Ethyl Malonate (la). "~ Reaction .

entry

2

1 2 3

2a 2b 2c

.

.

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temp (°C) 50 50 40

.

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3 .

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.

time (h) 36 12 7

yield (%) 82 52 77

%ee 76 2 70

a~Mesylate:Nucleophile:Cs2CO 3 = 1:3:3. In conclusion, on the basis of the present study together with the previous ones, the synthetic usefulness of the CsF method can be summarized as follows. (1) Both secondary mesylates and tosylates are employable as substrates. (2) A variety of oxygen-, sulfur-, nitrogen- and carbon-nucleophiles are incorporated on the asymmetric carbon center with perfect inversion of the starting secondary alcohol derivatives.

(3) Three

equivalents of nucleophiles and CsF are enough to effect the acceptable results with both yield and %ee. Moreover, use of one equivalents of these compounds also works satisfactorily in many cases. (4) Base- and acid-sensitive groups remain intact in the reaction.

(5) Sterically demanding substrates undergo smooth

transformation. EXPERIMENTAL SECTION

General. Commercially available CsF and malonic ester derivatives were used as received. Mesylates, (S)l a , aa (S)-lb, 8" l e , TM and l d , TM and tosylates, (S)-4a 7 and (S)-4b 6, were prepared according to the literature methods. All reactions were run under dry nitrogen. DMF was distilled from calcium hydride. CsF-Proraoted Reaction (Typical Procedure). To a reaction flask was added CsF (152 mg, 1.0 mmol). The flask was heated at 200 °(2 in vacuo for 15 rain and then filled with nitrogen while being cooled to room temperature. To this flask was added 2b (143 mg, 1.3 mmol) and DMF (4 ml). After the mixture was stirred for 20 min, 1 in 1.0 ml of DMF was added. The reaction mixture was stirred at 50 °C for 12 h. The mixture was extracted with EtOAc and the organic layer was washed with NaI-ICO3 solution, brine to give 3ab (179 mg, 85%): tH NMR (CDCI 3) 5 1.17 (t, 3H, J = 7.1 Hz), 1.48 (d, 3H, J = 7.1 Hz), 3.78 (q, 1H, J = 7.1 Hz),

13638

J. O T E R A e t al.

4.11 (q, 2H, J = 7.1 Hz), 7.29-7.31 (m, 3H), 7.45-7.47 (m, 2H); J3C NMR (CDCI3) ~i 13.9, 17.3, 45.2, 61.0, 127.8, 128.8, 132.9, 172.5; [(/,]D 14 1 3 2 . 5 ° (CHC13, c 0.9); 99 %ee based on IH NMR with Eu(hfc) 3. Other reactions were carried out analogously. The products were confirmed by comparison of their spectral data with reported ones. 3aa: 19~H NMR (CDC13) ~ 1.28 (t, 3H, J = 7.1 Hz), 1.63 (d, 3H, J = 7.1 Hz,), 4.24 (q, 2H, J = 7.1 Hz), 5.31 (q, 1H, J = 7.1 Hz), 7.41-7.48 (m, 2H), 7.55-7.61 (m, 1H), 8.06-8.12 (m, 2H); ~3C NMR (CDCI3) 14.0, 16.9, 61.2, 69.1, 128.3, 129.7, 133.1, 165.8, 170.7; [t~]D~7 -14.9 ° (CHC13, c 1.2); >99 %ee based on ~H NMR with Eu(hfc)3. 3ac: ~2IH NMR (CDC13) 8 1.27 (t, 3H, J = 7.1 Hz), 1.51 (d, 3H, J = 7.5 Hz), 2.35 (s, 3H), 4.15-4.26 (m, 3H); t3C NMR (CDCI3) ~ 13.9, 17.5, 30.1, 40.9, 61.5, 171.8, 193.8; [~]D~6 120.8° (CHC13, c 1.2); 99 %ee based on ~H NMR with Eu(hfc) 3. 3ad: 2° ~H NMR (CDC13) ~ 1.24 (t, 3H, J = 7.1 Hz), 1.70 (d, 3H, J = 7.4 Hz), 4.18-4.25 (m, 2H), 4.97 (q, 1H, J = 7.4 Hz), 7.73-7.77 (m, 2H), 7.85-7.88 (m, 2H); ~3C NMR (CDC13) 8 14.0, 15.1, 47.5, 61.7, 123.3, 131.9, 134.0, 167.3, 169.5; 90 %ee based on ~H NMR with Eu(hfc) 3. 3ae: 2j IH NMR (CDC13) 6 1.32 (t, 3H, J = 7.1 Hz), 1.48 (d, 3H, J = 7.1 Hz), 3.93 (q, 1H, J = 7.1 Hz), 4.25 (q, 2H, J = 7.1 Hz); ~3C NMR (CDCI3) ~5 13.9, 16.5, 57.2, 61.6, 170.8; [¢X]D~5 16.0° (hexane, c 1.1); 99 %ee based on ~H NMR with Eu(hfc) 3. 3af: 22 ~H NMR (CDC13) ~ 1.25 (t, 3H, J = 7.1 Hz), 1.62 (d, 3H, J = 6.8 Hz), 4.22 (q, 2H, J = 7.1 Hz), 4.75 (q, 1H, J = 6.8 Hz), 6.89 (d, 2H, J = 1.0 Hz), 6.94-7.00 (m, 1H), 7.25-7.30 (m, 2H); ~3C NMR (CDC13) ~ 14.0, 18.4, 61.1, 72.5, 115.0, 121.4, 129.4, 157.5, 172.1; >99 %ee (from the tosylates)based on IH NMR with Eu(hfc) 3. 3bb: 23 IH NMR (CDCI3) ~i 0.88 (t, 3H, J = 6.5 Hz), 1.21-1.35 (m, 8H), 1.27 (d, 3H, J = 6.5 Hz), 1.35-1.71 (m, 2H), 3.14-3.29 (m, IH), 7.2-7.6 (m, 5H); ~3C NMR (CDC13) ~ 14.1, 21.0, 22.6, 27.0, 29.1, 31.7, 36.5, 43.1, 126.5, 128.7, 131.7, 135.4; ; [t~]t)27 1.4° (CHC13, c 1.1); >99 %ee based on ~H NMR with Eu(hfc)3 after conversion of 3bb to (R)-2-octyl phenyl sulfone with m-CPBA. 3bc: 24 IH NMR (CDC13) ~ 0.88 (t, 3H, J = 7.0 Hz), 1.20 -1.43 (m, 8H), 1.29 (d, 3H, J = 7.0 Hz), 1.47-1.59 (m, 2H), 2.30 (s, 3H), 3.47-3.61 (m, 1H); ~3C NMR (CDCI3) 8 13.8, 21.1, 22.4, 26.8, 28.9, 30.4, 31.5, 36.3, 39.3, 195.4; [Ct]D25 6.5 ° (C6H6, c 1.2); >99 %ee based on ~H NMR with Eu(hfc) 3. 3bd: 25 tH NMR (CDCI3) 8 0.85 (t, 3H, J = 7.0 Hz), 1.11-1.37 (m, 8H), 1.46 (d, 3H, J = 7.1), 1.642.16 (m, 2H), 4.27-4.41 (m, 1H), 7.6-7.9 (m, 4H); ~3C NMR (CDC13) ~ 13.8, 18.4, 22.3, 26.5, 28.7, 31.4, 33.5, 47.2, 122.7, 131.8, 133.5, 168.2; [t~]D26 -17.2° (CHC13, c 1.0); >99 %ee as (R)-MTPA amide by IH NMR. 3be: 26 tH NMR (CDC13) ~ 0.87 (t, 3H, J = 7.1 Hz), 1.10-1.39 (m, 8H), 1.25 (d, 3H, J = 7.1 Hz), 1.35-1.58 (m, 2H), 3.39-3.49 (m, 1H); ~3C NMR (CDC13) 8 13.9, 19.3, 22.5, 26.0, 29.0, 31.6, 36.1, 57.9;

CsF in organic synthesis

13639

[oqD~7 -42.7 ° (CHC13, c 1.2); >99 %ee based on 1H NMR as (R)-MTPA amide which was produced by reduction of 3be with LiA1H4 followed by treatment with (S)-MTPAC1. 3cb: 27 ~H NMR (CDC13) ~ 0.87 (S, 9H), 0.96-1.04 (m, 1H), 1.43-1.58 (m, 4H), 1.64-1.73 (m, 2H), 1.95-1.98 (m, 2H), 3.60-3.63 (m, 1H), 7.12 (t, 1H, 7.2 Hz), 7.26 (t, 2H, 7.2 Hz), 7.37 (t, 2H, 7.2 Hz); ~3C NMR (CDC13) 5 22.0, 27.4, 31.3, 32.5, 45.1, 48.2, 126.1, 128.7, 130.9, 136.4; >99 %de based on ~H NMR. 3ce: 28 ~H NMR (CDC13) fi 0.85 (s, 9H), 0.95-1.03 (m, 1H), 1.21-1.32 (m, 2H), 1.44-1.53 (m, 2H), 1.54-1.61 (m, 2H), 1.88-1.93 (m, 2H), 3.86-3.87 (m, 1H); ~3C NMR (CDCI~) ~ 21.6, 27.4, 30.3, 32.5, 47.6, 57.4; >99 %de based on ~H NMR. 3db: 27 ~H NMR (CDC13) 5 0.83 (s, 9H), 0.97-1.10 (m, 3H), 1.26-1.35 (m, 2H), 1.78-1.84 (m, 2H), 2.05-2.12 (m, 2H), 2.92-3.01 (m, 1H); ~3C NMR (CDCI3) 8 27.5, 27.6, 32.3, 33.9, 46.6, 47.3, 126.5, 128.7, 131.8, 135.0; >99 %de based on ~H NMR. 6 a a : 29

IH

NMR (CDCI3) 5 1.16 (d,

3H,

J =

7.2

Hz),

1.18 (t,

3H,

J =

7.2

Hz

), 1.19 (t, 3H, J = 7.2 Hz), 1.21 (t, 3H, J = 7.2 Hz), 3.16 (qd, 1H, J = 7.2, 9.7 Hz), 3.71, (d, 1H, J = 9.7 Hz), 4.04-4.20 (m, 6H); ~3C NMR (CDCI3) ~i 13.9, 14.0, 15.0, 39.1, 54.6, 60.9, 61.6, 167.9, 168.0, 174.0; >99 %ee based on ~H NMR with Eu(hfc) 3. 6ab: 3° ~H NMR (CDC13) major diastereomer 8 1.29 (t, 3H, J = 7.1 Hz), 1.34 (t, 3H, J = 7.1 Hz), 1.42 (d, 3H, J = 7.2 Hz), 3.15 (qd, 1H, J = 7.2, 7.5 Hz), 4.01 (d, 1H, J = 7.5 Hz), 4.21 (q, 2H, J = 7.1 Hz), 4.28 (q, 2H, J = 7.1 Hz); minor diastereomer 8 1.28 (t, 3H, J = 7.1 Hz), 1.33 (t, 3H, J = 7.1 Hz), 1.43 (d, 3H, J = 7.3 Hz), 3.23 (qd, 1H, J = 7.3, 4.9 Hz), 3.75 (d, 1H, J = 4.9 Hz), 4.21 (q, 2H, J = 7.1 Hz), 4.29 (q, 2H, J = 7.1 Hz); ~3C NMR (CDCI3) major diastereomer 8 13.8, 13.9, 14.3, 39.2, 39.9, 61.5, 63.0, 114.7, 164.8, 172.0; minor diastereomer 5 13.8, 13.9, 14.3, 39.4, 40.4, 61.4, 62.8, 114.9, 164.6, 171.2; 91.0 %ee based on IH NMR with Eu(hfc) 3 6bail ~ ~H NMR (CDC13) ~ 0.88 (t, 3H, J = 7.0 Hz), 0.98 (d, 3H, J = 6.7 Hz), 1.27 (t, 6H, J = 7.0 Hz), 1.13-1.45 (m, 10H), 2.16-2.33 (m, 1H), 3.22 (d, 1H, J = 7.9 Hz), 4.19 (q, 4H, J = 7.0 Hz); ~3C NMR (CDCI3) ~ 13.9, 14.0, 16.9, 22.5, 26.7, 29.2, 31.7, 33.3, 34.3, 57.7, 60.9, 61.0, 168.8, 168.9; >99 %ee based on ~H NMR with Eu(hfc)3 6be: 32 ~H NMR (CDC13) 5 0.89 (t, 3H, J = 6.8 Hz), 1.22-1.40 (m, 8H), 1.31 (d, 3H, J = 7.0 Hz), 1.44-1.67 (m, 2H), 2.52-2.67 (m, 1H); ~3C NMR (CDCI3) ~ 13.8, 17.9, 22.4, 25.3, 26.8, 28.6, 31.4, 33.9, 122.9; >99 %ee based on ~H NMR as (R)-MTPA amide which was produced by reduction of 3be with LiA1H4 followed by treatment with (S)-MTPACI.

13640

J. OTERAet al.

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9. 10. 11. 12. 13. 14. 15.

16. 17. 18 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32.

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(Received in Japan 9 July 1997; accepted 4 August 1997)