Simmons-Smith reaction

The Simmons-Smith reaction is an organic reaction in which a carbenoid reacts with an alkene (or alkyne) to form a cyclopropane. [cite journal | author = Howard Ensign Simmons, Jr.; Smith, R.D. | title = 4-Substituted-2,3,5-pyrrolidinetriones | journal = J. Am. Chem. Soc. | year = 1958 | volume = 80 | pages = 532 | doi = 10.1021/ja01548a031.] [cite journal | author = Simmons, H.E.; Smith, R.D. | title = A New Synthesis of Cyclopropanes | journal = J. Am. Chem. Soc. | year = 1959 | volume = 81 | pages = 4256 | doi = 10.1021/ja01525a036] [cite journal | author = Denis, J.M.; Girard, J.M.; Conia, J.M | journal = Synthesis | year = 1972 | pages = 549 | doi = 10.1055/s-1972-21919 | title = Improved Simmons-Smith Reactions | volume = 1972] It is named after Howard Ensign Simmons, Jr. and R. D. Smith.

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Thus, cyclohexene, diiodomethane, and a zinc-copper couple (as iodomethylzinc iodide, ICH₂ZnI) yield norcarane (bicyclo [4.1.0] heptane). [OrgSynth | author = Smith, R. D.; Simmons, H. E. | title = Norcarane | collvol = 5 | collvolpages = 855 | prep = cv5p0855] [OrgSynth | author = Ito, Y.; Fujii, S.; Nakatuska, M.; Kawamoto, F.; Saegusa, T. | collvol = 6 | collvolpages = 327 | year = 1988 | prep = cv6p0327 | title = One-Carbon Ring Expansion Of Cycloalkanones To Conjugated Cycloalkenones: 2-Cyclohepten-1-one]

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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. [cite journal | author = Simmons, H. E. "et al." | journal = Org. React. | year = 1973 | volume = 20 | pages = 1 | format = Review] [cite journal | author = Girard, C.; Conia, J. M. | journal = J. Chem. Res. (S) | year = 1978 | pages = 182 | format = Review] 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: [cite journal | title = Stereochemistry and total synthesis of ()-ivangulin | author = Paul A. Grieco, Tomei Oguri, Chia-Lin J. Wang, and Eric Williams | journal = J. Org. Chem | year = 1977 | volume = 42 | pages = 4113 | doi = 10.1021/jo00445a027]

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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: [cite journal | author = Cohen, T.; Kosarych, Z. | title = 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 | journal = J. Org. Chem | year = 1982 | volume = 47 | pages = 4005 | doi = 10.1021/jo00141a047]

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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 [cite journal | title = A catalytic enantioselective reaction using a C2-symmetric disulfonamide as a chiral ligand: cyclopropanation of allylic alcohols by the Et2Zn-CH2I2-disulfonamide system | journal = Tetrahedron Letters | volume = 33 | issue = 18 | year = 1992 | pages = 2575–2578 | author = Hideyo Takahashi, Masato Yoshioka, Masaji Ohno and Susumu Kobayashi | doi = 10.1016/S0040-4039(00)92246-9] with a reaction of cinnamyl alcohol with diethylzinc, diiodomethane and a chiral disulfonamide in dichloromethane:

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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: [cite journal | title = Asymmetric Simmons–Smith Reaction of Allylic Alcohols with Al Lewis Acid/N Lewis Base Bifunctional Al(Salalen) Catalyst | author = Hiroaki Shitama and Tsutomu Katsuki | journal = Angew. Chem. Int. Ed. | year = 2008 | doi = 10.1002/anie.200705641 | volume = 47 | pages = 2450]

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References

External links

* [http://www.organic-chemistry.org/namedreactions/simmons-smith-reaction.shtm Simmons-Smith reaction at Organic Chemistry Portal]