Phosphonium salts cyclopropanes

Difluorocarbene can be conveniently generated at room temperamre by the addition of fluoride ion to bromodifluorophosphonium bromide and, provided that the solvents are scrupulously dry, can be trapped by alkenes [60], dienes [61] and cycloalkenes [62] (Figure 6.42). The phosphonium salt may be generated in situ, allowing cyclopropanation to be carried out in a one-pot process [60] (Figure 6.43). Addition of 18-crown-6 to the reaction medium enhances the solubility of the metal fluoride and allows cyclopropanation of less nucleophilic alkenes and alkynes to be performed [63] (Figure 6.44). 

The stereoselectivity of the attack of the enolate on the activated cyclopropane most likely is due to steric factors arising from the preferred pseudoaxial conformation of the incipient methyl group . In other words, the approach of the rather bulky phosphonium salt II is less perturbed by the methyl group when it rests on the opposite side of the molecule in the transition state, presumably in the pseudoaxial conformation, as portrayed in IX. This remarkable stereoselectivity has been put to good use in the synthesis of some natural products of the spirovetivane family. ... 

Schweitzer has synthesized alkylidene cyclopropanes by Wittig reaction with a cyclopropyl phosphonium salt. If, however, the electrophilic character of the cyclopropane is enhanced by a second acceptor group (e.g. CO2R, SR), suitable nucleophiles are able to attack the three-membered ring. The resulting ylid can form hetero- and carbocycles by an intramolecular Wittig reactionas demonstrated in equations 62 and 63. These annulation reactions have been applied to terpene and alkaloid preparations. 

There are various methods for the synthesis of cyclopropyltriphenylphosphonium bromides, the precursor of choice for the preparation of cyclopropylidenetriphenylphosphoranes. Interestingly, attempts to generate the former salt from cyclopropane derivatives, e.g. 1-bromocy-clopropane, have been unrewarding. One exception is the reaction of cyclopropyllithium with tetraphenylphosphonium bromide followed by elimination of benzene from the initial adduct. The intermediate phosphorane 5 was converted into phosphonium salt 13 by reaction with hydrogen bromide. 

Preparation.—A historical account of the development of the synthesis of methylenephosphoranes has been given. Details have appeared - of the use of epoxides in the generation of ylides from phosphonium salts. Weakly acidic salts are deprotonated by the anions such as XCHaCH20 formed by attack of the phosphonium covmter-anion on epoxide, but strongly acidic phosphonium salts are deprotonated more rapidly than these species are produced. The base in these cases must be either epoxide or original anion. Side-reactions in olefin syntheses using epoxides as base include acetal formation from aldehyde and epoxide, cyclopropane formation from ylide and epoxide, and decomposition of quinquecovalent phosphoranes, e.g. (1), formed from phosphonium salt and... 

The unique chemistry exhibited by vinyl phosphonium salts and sulphur ylides is married in a versatile synthesis of disubstituted cyclopropanes (Scheme 1), and... 

Substitution of a cyclopropane by two geminal electron-withdrawing groups makes the three-membered ring very susceptible to nucleophilic attack. The readily-prepared phosphonium salt (480) condenses with the p-keto-ester anion (479) to furnish the cyclopentene (481). Similar nucleophilic attack on cyclopropane-l,l-dicarboxylic ester derivatives has been adapted to the synthesis of several prostaglandins. ... 

Such reagents might, for example, be incorporated into annulation schemes since they have the ability of undergoing the formal equivalent of cycloaddition reactions. Among the real chemical species which have been developed along these lines are the cyclopropane derivatives 1 and 2. The phosphonium salt 1 reacts with / -... 

The reaction between the sodium salt of an a-formylcycloalkanone and the phosphonium cyclopropane has been found to produce spiro compound 605, together with minor amounts of the dihydrofuran 606 (equation 215). This reaction sequence has been used in the synthesis of spirovetivane sesquiterpenes. ... 

---