Wittig cyclopropanation

A project directed towards the synthesis of chrysanthemic acid enantiomers illustrates some of our recent work on cyclopropano-pyranosides. The sequence (Scheme 40) that had worked so well (25) for the preparation of the simple cyclopropyl ketone (169) from the methanol adduct (168) was not adaptable for preparation of the gem-dimethyl analogue (171). The photoaddition of isopropanol to (83) gave an excellent yield of (170), but efforts to convert this into (171) were not encouraging. However, the Wittig cyclopropanation (24) of epoxide (51) gave the ester (172) whose stereochemistry was deduced by two pieces of nmr data (a) the value J12 < 1 Hz (76) (see Scheme 4), and (b) a ten percent Nuclear Overhauser Effect between H-1 and the methyl protons. 

Some straightforward, efficient cyclopentanellation procedures were developed recently. Addition of a malonic ester anion to a cyclopropane-1,1-dicarboxylic ester followed by a Dieckmann condensation (S. Danishefsky, 1974) or addition of iJ-ketoester anions to a (l-phenylthiocyclopropyl)phosphonium cation followed by intramolecular Wittig reaction (J.P, Marino. 1975) produced cyclopentanones. Another procedure starts with a (2 + 21-cycloaddition of dichloroketene to alkenes followed by regioselective ring expansion with diazomethane. The resulting 2,2-dichlorocyclopentanones can be converted to a large variety of cyclopentane derivatives (A.E. Greene. 1979 J.-P. Deprds, 1980). 

Several steps are involved in these reactions. First, the enolate of the (1-kelocstcr opens the cyclopropane ring. The polarity of this process corresponds to that in the formal synthon B because the cyclopropyl carbons are electrophilic. The product of the ringopening step is a stabilized Wittig ylide, which can react with the ketone carbonyl to form the carbocyclic ring. 

To prepare ectocarpene 535 and desmarestene 536 which are examples of plant chemoattractants, synthetic approaches which can be named cyclopropanation-Cope rearrangement (equation 209) and Wittig reaction-Cope rearrangement (equation 210), respectively, were employed261. It suffices to say that the end products 536 and 537 were isolated in high enantiomeric purity (>94% ee). 

The transition metal-catalyzed cyclopropanation of alkenes is one of the most efficient methods for the preparation of cyclopropanes. In 1959 Dull and Abend reported [617] their finding that treatment of ketene diethylacetal with diazomethane in the presence of catalytic amounts of copper(I) bromide leads to the formation of cyclopropanone diethylacetal. The same year Wittig described the cyclopropanation of cyclohexene with diazomethane and zinc(II) iodide [494]. Since then many variations and improvements of this reaction have been reported. Today a large number of transition metal complexes are known which react with diazoalkanes or other carbene precursors to yield intermediates capable of cyclopropanating olefins (Figure 3.32). However, from the commonly used catalysts of this type (rhodium(II) or palladium(II) carboxylates, copper salts) no carbene complexes have yet been identified spectroscopically. 

Rotane was first synthesized by Rippol and Conia29. The key steps included the synthesis of dispirononanone 13 (equation 11). Condensation of 13 with formaldehyde provided the tetrahydroxymethyl derivative 32, which was converted into the tetraspiro compound 33 by tosylation-bromination followed by reductive cyclization. Subsequent Wittig methylenation and cyclopropanation of the ketone 33 completed the synthesis (equation 30). 

Ylides of other elements have been used much less commonly than sulfur ylides in cyclopropanations. Rather, other ylides are better known for their uses in other types of reactions, the best example being the use of phosphonium ylides in the Wittig reaction with carbonyl compounds to give alkenes. Nonetheless, some cases of cyclopropanations have been reported with phosphonium ylides and the related arsenic derivatives. Examples are given in Table 9. 

Reviews have featured epoxidation, cyclopropanation, aziridination, olefination, and rearrangement reactions of asymmetric ylides 66 non-phosphorus stabilized carbanions in alkene synthesis 67 phosphorus ylides and related compounds 68 the Wittig reaction 69,70 and [2,3]-Wittig rearrangement of a-phosphonylated sulfonium and ammonium ylides.71 Reactions of carbanions with electrophilic reagents, including alkylation and Wittig-Homer olefination reactions, have been discussed with reference to Hammett per correlations.72... 

This topological rule readily explained the reaction product 211 (>90% stereoselectivity) of open-chain nitroolefins 209 with open-chain enamines 210. Seebach and Golinski have further pointed out that several condensation reactions can also be rationalized by using this approach (a) cyclopropane formation from olefin and carbene, (b) Wittig reaction with aldehydes yielding cis olefins, (c) trans-dialkyl oxirane from alkylidene triphenylarsane and aldehydes, (d) ketenes and cyclopentadiene 2+2-addition, le) (E)-silyl-nitronate and aldehydes, (f) syn and anti-Li and B-enolates of ketones, esters, amides and aldehydes, (g) Z-allylboranes and aldehydes, (h) E-alkyl-borane or E-allylchromium derivatives and aldehydes, (i) enamine from cyclohexanone and cinnamic aldehyde, (j) E-enamines and E-nitroolefins and finally, (k) enamines from cycloalkanones and styryl sulfone. 

The DPM rearrangement has provided a simple route for the construction of the carbon skeleton present in the sesquiterpenoid taylorione, isolated from Mylia taylori [46]. Thus, direct irradiation of the i>cyclopentenone 62 results in efficient, regiospecific DPM reaction affording the r[Pg.177]

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