Stereochemistry cyclopropanes

The stereoselection in the cyclization of each diastereomer was examined independently. The stereochemical outcome of the cyclization should be predictable based on our assumption regarding the relationship between enolate stereochemistry and cyclopropane stereochemistry, the principles of asymmetric, intermolecular alkylation of optically active amides (9-13) and the assumption that the mechanism of cyclopropane formation involves a straightforward back-side, %2 reaction. In the case of the major diastereomer, the natural tendency of the enolate to produce the cis-cyclopropane will oppose the facial preference for the alkylation of the chiral enolate. Consequently, poorer stereochemical control would be ejected in the ring closure. In the minor diastereomer these two farces are working in tandem, and high degrees of stereocontrol should result. 

The usefulness of this transformation first became apparent when it was discovered that some chiral cyclopropane-containing pyrethroids were highly effective insecticides. More importantly, the biological activity of these compounds was directly related to the cyclopropane stereochemistry [4]. One of the most ef-... 

The copper-catalyzed methylene transfer from sulfonium ylidcs to electron-rich olefins proceeds stereospecifically and probably involves a methylene copper complex15. Sulfonium, sulfoxonium, and (dialkylamino)sulfoxonium ylides are nucleophilic species and, in uncatalyzed reactions, only good Michael acceptors are attacked16 (see also Vol. IV/3, p 139 and Vol. E 11 2, p 1422). The cyclopropanation proceeds stepwise via a zwitterion, and therefore the olefin configuration is not necessarily reflected in the cyclopropane stereochemistry. Thus, both dimethyl ( )- or (Z)-2-butenedioate react with dimethylamino(phenyl)sulfoxonium methylide to give the //ww-substituted cyclopropane 4 only1. ... 

Linear correlations in the stoicheoimetric cyclopropanation by W(CHPh)(C0)5 with alkenes in a comparison with the catalytic reactions of Rh2(0Ac) suggest a unifying mechanism. Cyclopropanation stereochemistry is determined by interactions in the TT-complex and at the ring forming stage. 

Ethyl-5-methyl (3R, 5R) and (3R, 55) derivatives Elucidation of the stereochemistry of the pyrazoline-> cyclopropane reaction 77JA2740... 

The stereochemistry of the resulting cyclopropane product (.s vn vs anti) was rationalized from a kinetic study which implicated an early transition state with no detectable intermediates. Approach of the alkene substrate perpendicular to the proposed carbene intermediate occurs with the largest alkene substituent opposite the carbene ester group. This is followed by rotation of the alkene as the new C—C bonds begin to form. The steric effect of the alkene substituent determines... 

Chemo- and stereoselective reduction of (56) to (55) is achieved In highest yield by sodium borohydride in ethanol. The isolated ketone is reduced more rapidly than the enone and (55) is the equatorial alcohol. Protection moves the double bond out of conjugation and even the distant OH group in (54) successfully controls the stereochemistry of the Simmons-Smith reaction. No cyclopropanation occurred unless the OH group was there. Synthesis ... 

The enyne cross metathesis was first developed in 1997 [170,171]. Compared to CM it benefits from its inherent cross-selectivity and in theory it is atom economical, though in reality the aUcene cross-partner is usually added in excess. The inabihty to control product stereochemistry of ECM reactions is the main weakness of the method. ECM reactions are often directly combined with other transformations like cyclopropanation [172], Diels-Alder reactions [173], cychsations [174] or ring closing metathesis [175]. 

Examples of the use of dimethylsulfonium methylide and dimethylsulfoxonium methylide are listed in Scheme 2.21. Entries 1 to 5 are conversions of carbonyl compounds to epoxides. Entry 6 is an example of cyclopropanation with dimethyl sulfoxonium methylide. Entry 7 compares the stereochemistry of addition of dimethylsulfonium methylide to dimethylsulfoxonium methylide for nornborn-5-en-2-one. The product in Entry 8 was used in a synthesis of a-tocopherol (vitamin E). 

From the point of view of both synthetic and mechanistic interest, much attention has been focused on the addition reaction between carbenes and alkenes to give cyclopropanes. Characterization of the reactivity of substituted carbenes in addition reactions has emphasized stereochemistry and selectivity. The reactivities of singlet and triplet states are expected to be different. The triplet state is a diradical, and would be expected to exhibit a selectivity similar to free radicals and other species with unpaired electrons. The singlet state, with its unfilled p orbital, should be electrophilic and exhibit reactivity patterns similar to other electrophiles. Moreover, a triplet addition... 

Addition reactions with alkenes to form cyclopropanes are the most studied reactions of carbenes, both from the point of view of understanding mechanisms and for synthetic applications. A concerted mechanism is possible for singlet carbenes. As a result, the stereochemistry present in the alkene is retained in the cyclopropane. With triplet carbenes, an intermediate 1,3-diradical is involved. Closure to cyclopropane requires spin inversion. The rate of spin inversion is slow relative to rotation about single bonds, so mixtures of the two possible stereoisomers are obtained from either alkene stereoisomer. 

The threo stereoisomer was the major product obtained by the synthesis in Scheme 13.14. This stereochemistry was established by the conjugate addition in Step A, where a significant (4-6 1) diastereoselectivity was observed. The C(4)-C(7) stereochemical relationship was retained through the remainder of the synthesis. The other special features of this synthesis are in Steps B and C. The mercuric acetate-mediated cyclopropane ring opening was facilitated by the alkoxy substituent.19 The reduction by NaBH4 accomplished both demercuration and reduction of the aldehyde group. 

Based on these mechanisms and ligand structures, various transition-state models to explain the stereochemistry of asymmetric cyclopropanation reactions have been proposed. For details, see the reviews17- 1 and the references cited for Figure 12. 

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