Simmons-Smith reaction

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The Simmons-Smith reaction is an organic reaction in which a carbenoid reacts with an alkene (or alkyne) to form a cyclopropane.[1][2][3] It is named after Howard Ensign Simmons, Jr. and R. D. Smith.


Simmons-Smith reaction mechanism

Thus, cyclohexene, diiodomethane, and a zinc-copper couple (as (iodomethyl)zinc iodide, ICH2ZnI) yield bicyclo[4.1.0]heptane.[4][5]

An example of the Simmons-Smith reaction

Alternatively, diethylzinc is used instead of the zinc-copper couple.

The Simmons-Smith reaction is generally subject to steric effects, and thus cyclopropanation usually takes place on the less hindered face.[6][7] However, when hydroxy substituents are present on chiral carbons, the zinc coordinates with the hydroxy substituents, directing cyclopropanation to the same face, which may or may not be sterically favorable [8]:

An example of a stereoselective Simmons-Smith reaction

The Simmons-Smith reagent, namely diiodomethane and diethylzinc, can react with allylic thioethers to generate sulfur ylides, which can subsequently undergo a 2,3-sigmatropic rearrangement, and will not cyclopropanate an alkene in the same molecule unless excess Simmons-Smith reagent is used[9]:

An example of the use of the Simmons-Smith reagent to generate a sulfur ylide

[edit] Asymmetric Simmons-Smith reaction

Although asymmetric cyclopropanation methods based on diazo compounds (see bisoxazoline ligand) exist since 1966, the asymmetric Simmons-Smith reaction was introduced in 1992 [10] with a reaction of cinnamyl alcohol with diethylzinc, diiodomethane and a chiral disulfonamide in dichloromethane:

Asymmetric Simmons-Smith

The hydroxyl group is a prerequisite serving as an anchor for zinc. In another version of this reaction the ligand is based on salen and Lewis acid DIBAL is added [11]:

Asymmetric Simmons-Smith Shitama 2008

[edit] References

  1. ^ Howard Ensign Simmons, Jr.; Smith, R.D. J. Am. Chem. Soc., 1958, 80, 5323.
  2. ^ Simmons, H.E.; Smith, R.D. J. Am. Chem. Soc., 1959, 81, 4256.
  3. ^ Denis, J.M.; Girard, J.M.; Conia, J.M. Synthesis, 1972, 549.
  4. ^ Smith, R. D.; Simmons, H. E. Organic Syntheses, Coll. Vol. 5, p.855 (1973); Vol. 41, p.72 (1961). (Article)
  5. ^ Ito, Y.; Fujii, S.; Nakatuska, M.; Kawamoto, F.; Saegusa, T. Organic Syntheses, Coll. Vol. 6, p.327 (1988); Vol. 59, p.113 (1979). (Article)
  6. ^ Simmons, H. E. et al. Org. React. 1973, 20, 1. (Review)
  7. ^ Girard, C.; Conia, J. M. J. Chem. Res. (S) 1978, 182. (Review)
  8. ^ Grieco et al. J. Org. Chem. 1977, 42, 4113.
  9. ^ Cohen, T.; Kosarych, Z. J. Org. Chem. 1982, 47, 4005.
  10. ^ A catalytic enantioselective reaction using a C2-symmetric disulfonamide as a chiral ligand: cyclopropanation of allylic alcohols by the Et2Zn-CH2I2-disulfonamide system Tetrahedron Letters, Volume 33, Issue 18, 28 April 1992, Pages 2575-2578 Hideyo Takahashi, Masato Yoshioka, Masaji Ohno and Susumu Kobayashi doi:10.1016/S0040-4039(00)92246-9
  11. ^ Asymmetric Simmons–Smith Reaction of Allylic Alcohols with Al Lewis Acid/N Lewis Base Bifunctional Al(Salalen) Catalyst Hiroaki Shitama and Tsutomu Katsuki Angew. Chem. Int. Ed. 2008, doi:10.1002/anie.200705641

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