2225
J. Org. C h e m . 1991,56, 2225-2234
Diastereodifferentiation in SNZ'Additions of Methylcuprates to Nonracemic Acyclic Vinyloxiranes James A. Marshall* and Bruce E. Blough Department of Chemistry, The University of South Carolina, Columbia, South Carolina 29208
Received September 13, 1990 SN2' additions of Me2CuLi, MeCu(CN)Li, and Me2Cu(CN)Li2to the 2s and 2R alkoxy cis-(Z)- and -(E)vinyloxiranes 8, 9, 13, and 14 were examined as possible routes to acyclic subunits of polypropionate natural products. Highest antksyn ratios were found for the (2s)- and (2R)-hydroxy-(E')-vinyloxiranes13a and 14a followed by the (2R)-MTM ether analogue 14c. In both cases Me2CuLigave higher ratios than either of the cyanocuprates (>991 vs 14:l for 13a/13b and >401 vs -241 for 14c).
Recent studies have shown that appropriately substituted acyclic vinyloxiranes undergo highly anti selective s N 2 ' displacements with methylcuprates to afford allylic alcohols which can be further elaborated to subunits of polypropionate natural products.14 For example, the cis-(2)-vinyloxirane I affords the SN2'products I1 and I11 with 99% anti stereoselectivity (eq l).l Likewise, the
VI1 (Eor 2, * = S or R) OH
OH
OR1
BnO&,Me I I
Me
IX
VI11
I (cis-2)
1
BnO,
he
he I11 (6%)
I1 (94%)
cis-(@ isomer Iv yields the analogous SN2' products v and VI with 96% anti selectivity (eq 2). These reactions are
4
y-
BnO
R=H MhCuLi
Me
(57%)
OR IV (&-E)
OH
B
n
o
OH
T f M+ eO +n B
Me..
OR
RO
v (84%)
(2)
plications of this methodology in the synthesis of macrolides and related natural p r ~ d u c t s . ~ Representative vinyloxiranes were prepared as outlined in Scheme I starting from the knoyn epoxy aldehyde 2.' Corey-Fuchs Wittig condensation with CBr4-Ph3P afforded the vinylidene dibromide 3 in high yieldnB This was subjected to sequential dehydrobromination-debromination according to Nicolaou.' Addition of acetaldehyde to the resulting lithio acetylide intermediate afforded the diastereomeric alcohols 5a and 6a as a 1:l inseparable mixture. Enriched samples of the (2S)-alcohol 5a could be secured through oxidation of the mixture to ketone 7 and reduction of 7 with (S)-BINAL-H8or entChirald-LAHSg The resulting ca. 4 1 mixture of S and R alcohols 5a and 6a could not be separated. The corresponding TBS ethers 5b/6b and MTM ethers 5c/6c were likewise inseparable. Mixtures enriched in the 2R diastereomers 6a-c (ca. 3:l) were secured through reduction of ketone 7 with (R)-BINAL-H8 or Chirald-LAHg and subsequent ether formation. These mixtures were hydrogenated to the corresponding inseparable mixtures of (2)-allylic alcohols and ethers 8 and 9. The absolute stereochemistry of the carbinyl center was ascertained by 'H NMR analysis of the O-methylmandelates.'O The (E)-vinyloxiranes 13-14 were readily prepared starting from enone 12,the Horner-Emmons product of aldehyde 2." Reduction of this enone with (S)-BINAL-H
VI (16%)
most efficient with the free alcohols (vs TBS ethers) suggestive of an OH directing effect. The present investigation was undertaken to examine the stereochemical role of allylic alcohol and ether substituents on the diastereoselectivity of SN2' displacements in vinyloxiranes such as VI1 (eq 3). These studies set the stage for further ap(1) Marehall, J. A.; Trometer, J. D.; Blough, B. E.; Crute, T. D. J. &g. Chem. 1988,53,4274. (2) Marshall, J. A.; Trometer, J. D. Tetrahedron 1989,45, 391. (3) Marshall, J. A.; Blough, B. E. J. Org. Chem. 1990,55, 1540. (4) Marshall, J. A. Chem. Reu. 1989,89,1603.
0022-3263/91/1956-2225$02.50/0
(5) Cf.: Masamune, S. Aldrichimica Acta 1978,11,23. Hoffmann, R. W . Angew. Chem., Znt. Ed. Engl. 1987,26,489. ( 6 ) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 3769. (7) Nicolaou, K. C.; Prasad, C. V. C.; Somers, P. K.; Hwang, C.-K. J. Am. Chem. SOC.1989,111,5330. (8) Noyori, R.; Tomino, I.; Tanimoto, Y.; Nishizawa, M. J. Am. Chem.
SOC.1984,106,6709. (9) Yamaguchi, S.; Mosher, H.S. J. Org. Chem. 1973,38,1870. Chi-
rald ia available from Aldrich Chemical Co., Milwaukee, WI. The enantiomer was obtained from Eli Lilly and Co. to whom we are grateful. (10)Trost, B. M.; Belletire, J. L.; Godleski, S.; McDougal, P. G.; Balkovec, J. M.; Baldwin, J. J.; Christy, M. E.; Ponticello, G. S.; Varga, S. L.; Springer, J. D. J. Org. Chem. 1986, 51, 2370. (11) Cf.: Blancheite, M. A.; Choy, W.; Davis, S. T.; Easenfield, A. P.; Masamune, S.;Roush, W. R.; Sakai, T. Tetrahedron Lett. 1984,%, 2183.
0 1991 American Chemical Society
2226 J. Org. Chem., Vol. 56, No. 6, 1991
Marshall and Blough Table I. (2)-Vinyloxiranes
Bnow syn sN2'
anti s N 2 '
Bm%
"MeCu"
ke
16
Brio+ Me
1
2 3 4 5
a Starting
R TBS TBS
series b b
TBS
b
MTM MTM
c
MeCd B B C B C
c
n
O
w
18
21
22
Me 20
yield 100 94 96 97 97
17
OH
BnO
Bn~+
19
8:9 19:81 80:20 80:20 76:24 12:88
B
Me
15
9
entry
SN2
BnO
BnO
8
elimination
elim (17/21)
SN2 (18 or 22)
-
-
SN2' 100 100 5 87 65
6
95 7 32
3
15 17.4 72.1 61.2 12.3
SN2' products 16 19 2.0 35.8 8.4 11.2 14.9 11.2 12:1
0.9:l 2.1:l
material was recovered from reactions employing MezCuLi. B = MeCu(CN)Li in EBO. C = MezCu(CN)Lizin EBO.
Table 11. (E)-Vinyloxiranes
BnoToR anti sN2'
"MeCu"
B
~
n
13
O
syn s N 2 '
w
BnO-";/tp:
16
"MeCu"
BnO+
entry 1 2 3 4 5 6 7 8 9 O A
'OR 13:14 2872 28~72 2872 25:75 25:75 2575 2575 25:75 2575
MeCu"
yield
H H H
a a a
A B
95 100 87
TBS TBS TBS MTM MTM MTM
b b b c c
c
C A B C
A B C
Brio+
ke 19
series
90 99 86 86 100 96
18
BnO
20
R
21
BnO+
Me 14
BnO-
15
BnO+
elim (17121)
-
SN2 (18 or 22) 18 29
14 2 95 7 100
38 7 2 7
-
SN2
elimination
17
sN2' 82 71 62 79 96 5 86
100
-
15
