Simmons-Smith epoxidation

A novel-in-situ preparation of an epoxidation reaction (Simmons-Smith Epoxidation) ... 

Simmons-Smith cyclopropanation of triene 423 delivers a triscyclopropyl hydrocarbon which exhibits chiral fluxional properties On epoxidation, a mixture of two triepoxides results these rearrange rapidly under a variety of conditions to 424, the first topologically nonplanar molecule The reaction path for this iso-... 

Androstenolone, 1, can be transformed microbiologically to the 7a,15a-dihy-droxy derivative 2 by the action of Colletotrichium Uni. During formation of the acetal (3), inversion takes place on C-7. Acidic cleavage of 3 results in the triol, 4, which can also be produced by direct acidic catalysis from 2 [12,13]. After selective protection to the 3/l,15a-dipivalate (5), the 15/1,16/1-methylene compound, 6, can be synthetized, and then stereoselectively transformed to the 5/ ,6/ -epoxide, 7. This reacts with triphenylphosphine and tetrachloromethane in pyridine to produce the 7a-chloro derivative, 8. On treatment with zinc and acetic acid, 8 can be converted to the key compound 9, which has a 5/i-hydroxy-6-ene structure. Compound 9 can then be methylenated stereoselectively in the 6/1,7/1 position by the Simmons-Smith method. The last three steps - 10 —> 11 —> 12 — drospirenone -include the build-up of the spironolactone ring, after which water is lost from the molecule and oxidation affords drospirenone. 

The examples mentioned above illustrate the progress in the field of stereocontrolled cyclopropanation. Nowadays, the asymmetric Simmons Smith cyclopropanation may well be mentioned in the line with other asymmetric reactions like epoxidation or dihydroxylation. Fligh enan-tioselectivity and diastereoselectivity can be... 

A cis addition mechanism is generally accepted for the reaction, because cis addition to an olefinic bond generally occurs with predominant attack at trans bonds, and the Simmons-Smith reagent attacks preferentially one of the trans olefinic bonds of trans,trans,cis-1,5,9-cyclodode-catriene and then the cis double bond of the monoadduct (378). The close correspondence in relative rates of olefins for the cyclopropane formation by the Simmons-Smith reaction with those for diimide reduction and peroxide epoxidation supports the concept 409). The latter two reactions are generally considered to proceed via cis addition. 

Chiral Ligand for Asymmetric Catalysis. Dimethyl l-tartrate is a demonstrated chiral ligand for the Ti -catalyzed asymmetric epoxidation of allylic alcohols (Sharpless epoxidation), and the Zn -mediated asymmetric cyclo-propanation of allylic alcohols (Simmons-Smith reaction), see lodomethylzinc Iodide Enantioselectivities in these reactions... 

SHAFIPLESS Asymmetne epoxidation 343 SHARPLESS Asymmetric d tydroxylalion 344 SHERAOSKY Rearrangement 345 SHESTAKOV Hydrazine synthesis 346 SIEGRIST Stilbene synthesis 347 SIMMONS - SMITH Cydopropane synthesis 348... 

Epoxides. This compound can be used instead of diiodomethane in the Simmons-Smith reaction. In the presence of a dialkyl sulfide and Et Zn aldehydes are converted to epoxides. 

The Simmons-Smith cyclopropanation reaction Stereochemically controlled epoxidations Regio- and Stereocontrolled Reactions with Nucleophiles Claisen-Cope rearrangements Stereochemistry in the Claisen-Cope rearrangement The Claisen-Ireland rearrangement Pd-catalysed reactions of allylic alcohols Pd-allyl acetate complexes Stereochemistry of Pd-allyl cation complexes Pd and monoepoxides of dienes The control of remote chirality Recent developments Summary... 

Many epoxidising agents, notably mCPBA and f-BuOOH/VO(acac)2, are capable of bonding to the OH group of an allylic alcohol. Epoxidation then occurs more readily on allylic alcohols and on the same side of the alkene as the OH groups, rather in the style of the Simmons-Smith reaction. The stereochemical outcome is easiest to see in cyclic allylic alcohols. Thus the cyclohexenol 120 gives the syn epoxide 121 cleanly with mCPBA via the conformation 122 in which the axial OH delivers the reagent to the same face of the alkene. 

Alcoholysis of epoxides. FeCl.i is an effective catalyst for the transformation. Oxidative cleavage of trimethylsiloxycyclopropanes. This method of enone generation, in combination with conjugate addition, enolate trapping, and Simmons-Smith reaction, complete the sequence of ring expansion that also incorporates a substituent at the y-position of a lower homolog. Thus 4-alkyl-2-cyclohexenones are readily prepared from cyclopentenone. 

Reaction of a-hydroxy-ketones (e.g. 275) with the Simmons-Smith reagent replaces the carbonyl group by a methylene (276) or ethano-group (277), depending upon the conditions employed. Bromomethyl-lithium in THF reacts with saturated aldehydes and ketones to give epoxides. Several steroid examples are given. 

Dimethylsulfonium methylide and dimethylsulfoxonium methylide also differ in their reachons with a,p-unsaturated carbonyl compounds. The sulfonium ylide reacts at the carbonyl group to form an epoxide, but with the sulfoxonium ylide a cyclopropane derivative is obtained by Michael addihon to the carbon-carbon double bond. The difference is again due to the fact that the kinehcally favoured reachon of the sulfonium yhde with the carbonyl group is irreversible, whereas the corresponding reaction with the sulfoxonium yhde is reversible, allowing preferenhal formahon of the thermodynamically more stable product from the Michael addihon. For example, the cyclopropane 112 is obtained from the reaction of dimethylsulfoxonium methylide with the enone 111 (1.105). Other methods for the formahon of cyclopropanes include carbene and Simmons-Smith-type... 

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