J. Org.Chem.
1986,51, 5259-5264
5259
Reduction of Vinyloxiranes with Samarium Diiodide. An Efficient Route to Functionalized Chiral, Nonracemic (E)-Allylic Alcohols’ Gary A. Molander,* Bruce E. La Belle, and Gregory Hahn Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215 Received August 11, 1986
Functionalized vinyloxiranes have been found to undergo facile reductive epoxide ring opening with samarium diiodide (SmI,) in THF in the presence of a proton source to provide (E)-allylic alcohols. Reactions are exceedingly rapid, taking place in most cases a t -90 “C within minutes. Ketones, esters, nitriles, and other functional groups survive these mild reaction conditions intact. Exclusive kinetic protonation of intermediates is observed. Furthermore, reactions take place under essentially neutral conditions, leading to exclusive generation of a single regio- and stereoisomeric (E)-allylic alcohol in nearly all cases. Unsaturated epoxide substrates for the reaction are readily available in chiral, nonracemic form, allowing unique access to optically active organic intermediates with a n array of chemodifferentiable functionality useful for further elaboration.
Development of synthetic methods which provide ready access to highly functionalized chiral, nonracemic substrates represents an important, continuing challenge for organic chemists. Perhaps the most significant contribution in this area during the past 10 years has been development of the Sharpless asymmetric epoxidation reaction., This procedure provides straightforward access to a wide variety of optically active epoxy alcohols suitable for further transformation into useful organic products? We have previously reported on samarium diiodide (Sm12)reduction of a,P-epoxy ketone substrates as a route to P-hydroxy ketone^.^ Utilizing the Sharpless asymmetric epoxidation technology2 and complementary methodologies5 to access requisite precursors, the SmI, reduction of qb-epoxy ketones represents an efficient entry into chiral, nonracemic aldol products difficult to access by more conventional means. Samarium diiodide is an extraordinarily efficient, yet chemoselective reducing agent.6 Recent studies have revealed that a variety of reduction^^,^,^ and coupling reactions6B can be accomplished by SmI, in the presence of a wide range of functional groups. We sought to utilize the selective nature of SmIz to effect reduction of functionalized vinyloxirane derivatives, pro(1) Lanthanides in Organic Synthesis. 5. (2) (a) Kabuki, T.; Sharpless, K. B. J.Am. Chem. Soc. 1980,102,5975. (b) Rossiter, B. E.; Kabuki, T.; Sharpless, K. B. J.Am. Chem. SOC.1981, 103, 464. (c) Martin, V. S.; Woodard, S. S.; Katsuki, T.; Yamada, Y.; Ikeda, M.; Sharpless, K. B. J. Am. Chem. SOC.1981, 103, 6237. (d) Pfenninger, A. Synthesis 1986,89. (e) Hanson, R. M.; Sharpless, K. B. J. Org. Chem. 1986, 51, 1922. (3) (a) Behrens, C. H.; Sharpless, K. B. Aldrichimica Acta 1983, 16, 67. (b) Sharpless, K. B.; Behrens, C. H.; Katsuki, T.; Lee, A. W. M.; Martin, V. S.; Takatani, M.; Viti, S. M.; Walker, F. J.; Woodard, S. S. Pure Appl. Chem. 1983,55,589. (c) Caron, M.; Sharpless, K. B. J. Org. Chem. 1985,50, 1557. (d) Chong, J. M.; Sharpless, K. B. J. Org. Chem. 1985,50, 1560. (e) Roush, W. R.; Adam, M. A. J . Org. Chem. 1985,50, 3752. (0 Behrens, C. H.; KO,S. Y.; Sharpless, K. B.; Walker, F. J. J. Org. Chem. 1985,50,5687. (9) Behrens, C. H.; Sharpless, K. B. J. Org. Chem. 1985,50, 5696. (4) Molander, G. A.;,Hahn, G. J. Org. Chem. 1986, 51, 2596. (5) (a) Hayashi, M.; Terashima, S.; Koga, K. Tetrahedron, 1981,37, 2797. (b) Adam, W.; Griesbeck, A.; Staab, E. Tetrahedron Lett. 1986, 27, 2839. (6) (a) Girard, P.; Namy, J. L.; Kagan, H. B. J. Am. Chem. SOC.1980, 102, 2693. (b) Natale, N. R. Org. Prep. Proced. Int. 1983, 15, 387. (c) Kagan, H. B.; Namy, J. L. In Handbook on the Physics and Chemistry ofRare Earths; Gschneidner, K. A., Jr., Eyring, L., U s . ; Elsevier Science: Amsterdam-New York, 1984. (d) Kagan, H. B. In Fundamental and Technological Aspects of Organo-f-Element Chemistry; Marks, T. J., Fragala, I. L., Eds.; D. Reidel: Boston, 1985. (7) Molander, G. A.; Hahn, G. J. Org. Chem. 1986, 51, 1135. (8) (a) Molander, G. A.; Etter, J. B. J. Org. Chem. 1986,51, 1778. (b) Fukuzawa, S.; Nakanishi, A,; Fujinami, T.; Sakai, S. J. Chem. Soc., Chem. Commun. 1986, 624. ( c ) Tabuchi, T.; Inanaga, J.; Yamaguchi, M. Tetrahedron Lett. 1986, 27, 1195. 0022-3263/86/1951-5259$01.50/0
viding a unique route to potentially useful organic intermediates. Three different reduction products of vinyloxiranes involving epoxide ring opening can be envisioned (Figure 1). Substitution of “hydride” a t the epoxide terminus of the four-carbon unit followed by protonation (pathway a) provides an allylic alcohol, whereas s N 2 reactivity of “hydride” a t the allylic site followed by protonation generates a homoallylic alcohol product (pathway b). Finally, SN2/attack of “hydride” at the olefinic terminus (1,4-addition, pathway c) may lead to either ( E ) -or (Z)-allylic alcohols isomeric to those generated by pathway a. All three reactivity patterns have been observed in simple substrates, although surprisingly few detailed studies have been conducted in attempts to bring about these useful reductions. Depending on substitution patterns of the substrate, LiA1H4 has been observed to react at all three sites.g BH,.THF and related reducing agents reduce unsaturated epoxides by pathway c to provide modest yields of (2)-allylic alcohols,1° and diisobutylaluminum hydride also reacts by this SN2’ fashion,gc although diastereoselectivity in this process is variable. Finally, Ca/NH,(l) and related dissolving metal reductions are reported to react with vinyloxiranes by an s N 2 ’ process, providing (E)-allylic alcohol products (pathway c ) . ~In~ each of these methods studied to date, only alkyl or aryl substituents were prgsent in the vinyloxirane substrates. We believed that SmI, would be far more tolerant of sensitive functional groups (Y) incorporated into these R,
6?.:\ 0
-
R’
R’
Y 1
Y
2
substrates than hydride or dissolving metal reductions, and would therefore enjoy a broader scope of applicability in generation of substituted allylic alcohols. It was hoped that the Sm12methodology might provide advantages in terms of diastereoselectivity as well. Combined with the (9) (a) Fuchs, R.; VanderWerf, C. A. J.Am. Chem. Soc. 1952, 74,5917. (b) Crandall, J. K.; Banks, D. B.; Colyer, R. A.; Watkins, R. J.; Arrington, J. P. J. Org. Chem. 1968,33,423. (c) Lenox, R. S.; Katzenellenbogen, J. A. J. Am. Chem. SOC.1973,95,957. (d) Parish, E. J.; Schroepfer, G. J., Jr. Tetrahedron Lett. 1976, 3775. (e) Garst, M. E. J . Org. Chem. 1979, 44, 1578. (10) (a) Zaidlewicz, M.; Uzarewicz, A.; Sarnowski, R. Synthesis 1979, 62. (b) Hutchins, R. 0.;Taffer, I. M.; Burgoyne, W. J. Org. Chem. 1981, 46, 5214. 0 1986 American Chemical Society
Molander et al.
5260 el. Org. Chem., Vol. 51, No. 26, 1986
HO
or
i"
HO
HO
Figure 1.
1 e Y-COOA H'
Figure 2.
Sharpless epoxidation reaction,2 Swern oxidation," and Wittig or Horner-Emmons chemistry,12 such a reduction R
R R
O
Wittip
- 1
CH0
would allow ready access to chiral, nonracemic organic intermediates with an array of chemodifferentiable functionality of great utility for further synthetic transformations. Herein we describe our successful efforts to achieve this selective reduction with SmI,.
Results and Discussion A t first glance, reduction of unsaturated epoxides to provide corresponding allylic alcohols with SmI, would appear to pose several significant problems. Although SmI, has been shown to react with isolated epoxides to generate olefins? reduction of vinyloxiranes to dienes was considered to be of minor concern. Our success in reducing a,@-epoxyketones to @-hydroxyketones without elimination to a,@-unsaturatedketones in the process4 gave us confidence that this "deoxygenation" would not pose a significant problem in most cases. Of greater concern was regio- and stereoselective generation of the olefin. Not only did the desired process require clean kinetic protonation of the intermediate (Figure 2 ) , but neutral reaction conditions were required to prevent isomerization in those instances where conjugating groups (e.g. Y = -COR, -COOR, -CN, -S02Ar)were utilized in the starting materials. Furthermore, although mechanistic analogies to dissolving metal reductions of similar substrates could be made,13 it was unclear what stereochemistry would be observed in the final products utilizing SmI, as the reductant. (11) Mancuso, A. J.; Swern, D. Synthesis 1981, 165. (12) March, J. Advanced Organic Chemistry, 3rd Ed.; Wiley-Inter-
science: New York, 1985; and references therein. (13) Kagan, H. B.; Namy. ,J. L.: Girard, P. Tetrahedron Suppl. 1981, 37, 175.
Finally, the scope of the reaction with respect to the types of groups Y that could be utilized in the reaction was of interest. While SmI, had previously been utilized t o cleanly reduce unsaturated carboxylic acids and esters to saturated derivatives, nonselective reduction of a,P-unsaturated aldehydes and ketones resulted in mixtures of carbonyl and alcohol products.6a Furthermore, isolated double bonds remained unchanged in the presence of SmI,, and so there was some question as to whether simple unsaturated epoxides (Y = H, alkyl) or those with electrondonating groups would be suitable substrates for reduction. Fortunately, nearly all of these concerns proved insignificant. We initiated our studies utilizing unsaturated epoxy ester substrates. As mentioned above, unsaturated esters were known to be suitable substrates for SmI, reduction,% and so effective reduction of the unsaturated epoxide by a mechanism similar to that depicted in Figure 2 was expected. Indeed, reactions in these cases were complete within seconds upon addition of substrates dissolved in THF/EtOH to Sm12in T H F at -90 "C (Table I). Both the reaction and workup are operationally quite simple. Unsaturated epoxide substrates in THF/EtOH are added to a solution of Sm12in T H F (samarium diiodide is generated in situ from samarium metal and 1,2-diiodoethanel4). The reaction is quenched within 10 min at -90 "C by addition of a pH 8 buffer. Simple extraction and Kugelrohr distillation or flash chromatography provides pure allylic alcohols in excellent yields. Elimination to dienes in this series poses little problem. In one instance (entry 61, minor amounts (
