[7440-19-9]  · Sm  · Samarium(0)  · (MW 150.36)

(used with diiodomethane to iodomethylate ketone and aldehyde substrates;2 cyclopropanates esters and a-halo ketones in the presence of diiodomethane to generate the one-carbon homologated product;2a,b,3 promotes the selective and directed cyclopropanation of allylic alcohols4-6)

Physical Data: mp 1072 °C; bp 1900 °C; d 7.470 g cm-3.

Form Supplied in: silvery metal; tarnishes on exposure to air; 40 mesh solid, ingot, chip, and foil (all commercially available).

Handling, Storage, and Precautions: moderately air- and moisture-sensitive. Should be handled accordingly under an inert atmosphere.

Iodomethylation of Ketones and Aldehydes.

Samarium metal may be utilized in conjunction with Diiodomethane to accomplish iodomethylation reactions.2 A wide variety of ketone and aldehyde substrates may be converted to the corresponding iodohydrins in good to high yields, providing an efficient means for one-carbon homologation (eq 1).

Even readily enolizable substrates such as cyclopentanone are converted to the corresponding iodohydrin in high yield upon treatment with samarium and diiodomethane (eq 2). Highly hindered ketones do not undergo iodomethylation; a,b-unsaturated carbonyl compounds subjected to these reaction conditions provide only moderate yields of the desired products.

Cyclopropanation of Esters and a-Halo Ketones.

Esters react with diiodomethane in the presence of samarium to afford the 1-substituted cyclopropanols, thereby providing a one-carbon homologation route to these molecules (eq 3).3 Likewise, a-halo substituted ketones react in a similar manner to provide cyclopropanols (eqs 4 and 5) via a Simmons-Smith-type cyclopropanation of the samarium enolate.2a,b

Directed Cyclopropanation of Allylic Alcohols.

A more efficient method of achieving cyclopropanation involves the use of Sm(Hg) in the presence of Chloroiodomethane (eq 6).4 The resulting samarium carbenoid generated under these reaction conditions reacts exclusively with allylic alcohols. Many other functionalities such as isolated alkenes, homoallylic alcohols, and other functionalized alkene substrates are inert under these reaction conditions.

Thus geraniol and nerol, when subjected to these reaction conditions, undergo cyclopropanation at only the allylic alkene, each producing a single diastereomeric product in excellent yield (eqs 7 and 8).4a,b Consequently, the Sm(Hg) protocol is preferential to the Simmons-Smith and related reagents which typically provide approximately 5% of byproducts resulting from cyclopropanation at the isolated alkene in geraniol. In addition to the exceptional chemoselectivity that this reagent possesses, the Sm(Hg) reagent displays excellent stereospecificity with respect to alkene geometry. Cyclopropanation of geraniol and nerol demonstrates that complete stereospecificity is obtained when subjected to the Sm(Hg) reagent.

Use of metalated alkenes containing tin or silicon substituents also react with excellent diastereoselectivity under similar reaction conditions, providing highly functionalized cyclopropanes (eq 9).4d The stannylated product may be transmetalated and the resulting lithium anion may be reacted with various electrophiles, thereby providing a route to diastereomers inaccessible by direct cyclopropanation (eq 10).

The samarium amalgam-mediated cyclopropanation has been used in the synthesis of 1,25-dihydroxycholecalciferol to generate the cyclopropyl alcohol stereospecifically and in high yield (eq 11).5 Likewise, the desired stereochemistry was generated under the influence of the two stereogenic centers on the (R,R)-2,3-butanediol acetal (eq 12).5

The Sm(Hg) method may also be utilized to perform ethylidenation reactions (eq 13).4a,b,6 This protocol is preferential since use of pyrophoric Diethylzinc may be avoided; additionally, the samarium-promoted reaction permits higher diastereoselectivities to be realized in this transformation.

1. (a) Molander, G. A. CRV 1992, 92, 29. (b) Molander, G. A. In The Chemistry of the Metal-Carbon Bond; Hartley, F. R., Ed.; Wiley: Chichester, 1989; Vol. 5, Chapter 8.
2. (a) Imamoto, T.; Takeyama, T.; Koto, H. TL 1986, 27, 3243. (b) Imamoto, T.; Hatajima, T.; Takiyama, N.; Takeyama, T.; Kamiya, Y.; Yoshizawa, T. JCS(P1) 1991, 3127. (c) Tabuchi, T.; Inanaga, J.; Yamaguchi, M. TL 1986, 27, 3891. (d) Imamoto, T.; Takiyama, N. TL 1987, 28, 1307.
3. Imamoto, T.; Kamiya, Y; Hatajima, T.; Takahashi, H. TL 1989, 30, 5149.
4. (a) Molander, G. A.; Etter, J. B. JOC 1987, 52, 3942. (b) Molander, G. A.; Harring, L. S. JOC 1989, 54, 3525. (c) Yamazaki, T.; Lin, J. T.; Takeda, M.; Kitazume, T. TA 1990, 1, 351. (d) Lautens, M.; Delanghe, P. H. M. JOC 1992, 57, 798.
5. Kabat, M.; Kiegiel, J.; Cohen, N.; Toth, K.; Wovkulich, P. M.; Uskoković, M. R. TL 1991, 32, 2343.
6. (a) Clive, D. L. J.; Daigneault, S. CC 1989, 332. (b) Clive, D. L. J.; Daigneault, S. JOC 1991, 56, 3801.

Gary A. Molander & Christina R. Harris

University of Colorado, Boulder, CO, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.