Simmons–Smith reaction

Simmons-Smith reaction

Simmons-Smith reaction in progress

The Simmons–Smith reaction is an organic cheletropic 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. Because the methylene unit is delivered to both carbons of the alkene simultaneously, the configuration of the double bond is preserved in the product and the reaction is stereospecific.[4]

Thus, cyclohexene, diiodomethane, and a zinc-copper couple (as iodomethylzinc iodide, ICH2ZnI) yield norcarane (bicyclo[4.1.0]heptane).[5][6]

Alternatively, diethylzinc may be 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.[7][8] However, when a hydroxy substituent is present in the substrate in proximity to the double bond, the zinc coordinates with the hydroxy substituent, directing cyclopropanation cis to the hydroxyl group (which may not correspond to cyclopropanation of the sterically most accessible face of the double bond):[9]

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:[10]

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 [11] with a reaction of cinnamyl alcohol with diethylzinc, diiodomethane and a chiral disulfonamide in dichloromethane:

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:[12]

References

  1. ^ Howard Ensign Simmons, Jr.; Smith, R.D. (1958). "A New Synthesis of Cyclopropanes from Olefins". J. Am. Chem. Soc. 80: 5323. doi:10.1021/ja01552a080. 
  2. ^ Simmons, H.E.; Smith, R.D. (1959). "A New Synthesis of Cyclopropanes". J. Am. Chem. Soc. 81: 4256. doi:10.1021/ja01525a036. 
  3. ^ Denis, J.M.; Girard, J.M.; Conia, J.M (1972). "Improved Simmons–Smith Reactions". Synthesis 1972: 549. doi:10.1055/s-1972-21919. 
  4. ^ Charette, A. B.; Beauchemin, A. Org. React. 2001, 58, 1. (doi:10.1002/0471264180.or058.01)
  5. ^ Smith, R. D.; Simmons, H. E., "Norcarane", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv5p0855 ; Coll. Vol. 5: 855 
  6. ^ Ito, Y.; Fujii, S.; Nakatuska, M.; Kawamoto, F.; Saegusa, T. (1988), "One-Carbon Ring Expansion Of Cycloalkanones To Conjugated Cycloalkenones: 2-Cyclohepten-1-one", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv6p0327 ; Coll. Vol. 6: 327 
  7. ^ Simmons, H. E. et al. (1973). (Review)Org. React. 20: 1. 
  8. ^ Girard, C.; Conia, J. M. (1978). (Review)J. Chem. Res. (S): 182. 
  9. ^ Paul A. Grieco, Tomei Oguri, Chia-Lin J. Wang, and Eric Williams (1977). "Stereochemistry and total synthesis of (±)-ivangulin". J. Org. Chem 42: 4113. doi:10.1021/jo00445a027. 
  10. ^ Cohen, T.; Kosarych, Z. (1982). "Complete regio- and stereospecificity in the Lewis acid catalyzed Diels-Alder reactions of (Z)-2-methoxy-1-(phenylthio)-1,3-butadienes. Conversion of the CS configuration of an adduct to the CC configuration at the allylic position by a [2,3] sigmatropic rearrangement". J. Org. Chem 47: 4005. doi:10.1021/jo00141a047. 
  11. ^ Hideyo Takahashi, Masato Yoshioka, Masaji Ohno and Susumu Kobayashi (1992). "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 33 (18): 2575–2578. doi:10.1016/S0040-4039(00)92246-9. 
  12. ^ Hiroaki Shitama and Tsutomu Katsuki (2008). "Asymmetric Simmons–Smith Reaction of Allylic Alcohols with Al Lewis Acid/N Lewis Base Bifunctional Al(Salalen) Catalyst". Angew. Chem. Int. Ed. 47: 2450. doi:10.1002/anie.200705641. 

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