Stereoselectivity Favorskii rearrangement

E. Lee and co-workers demonstrated that the chlorohydrin derived from (+)-carvone undergoes a stereoselective Favorskii rearrangement to afford a highly substituted cyclopentane carboxylic acid derivative. This intermediate was then converted to (+)-dihydronepetalactone. When the THP-protected chlorohydrin was treated with sodium methoxide in methanol at room temperature, the rearrangement took place with excellent stereoselectivity (10 1) and high yield. Interestingly, the major product was the thermodynamically less stable cyclopentanecarboxylate. 

Lee E, Yoon CH. Stereoselective Favorskii rearrangement of carvone chlorohydrin expedient s3mthesis of (-l-)-dihydrone-petalactone and (-l-)-iridomyrmecin. J. Chem. Soc, Chem. Commun. 1994 479-481. 

Favorskii rearrangement has also been used in the stereoselective synthesis of bicyclic esters (equation 188)987 and in novel very strained ring systems (equation 189)988. 

When 95 has been treated with sodium methoxide in methanol at room temperature, the Favorskii rearrangement occurred in a stereoselective manner and the cyclopentanecarboxylate 96 has been obtained in high yields as described in scheme 19. 

There have also been a number of investigations of the stereochemistry of the Favorskii rearrangement. Although several compounds show stereoselectivity, the general result is that these reactions give the stereoisomeric reaction products that... 

Scheme 7.5 Stereoselective ring-opening (retention) of a cyclopropanone under conditions of the Favorskii rearrangement.

An intramolecular (4+3)-cycloaddition illustrates the potential of the quasi-Favorskii approach in the preparation of complex ring systerns.Reaction of readily available alcohol 80 with triflic anhydride afforded the cycloadduct 81 stereoselectively in 65% yield (Scheme 7.21 V Treatment of this compound with lithium aluminum hydride (LAH) afforded an essentially quantitative yield of alcohol 82 from a sequence of reduction, quasi-Favorskii rearrangement, and further reduction. 

A Stereoselective Synthesis volume of the Science of Synthesis series has reviewed the alkylation and allylation of carbonyl and imino groups, as well as the enantio-selective addition of metal alkynylides to imino and carbonyl compounds. Recent advances in Favorskii rearrangement, Sonogashira reactions, and catalytic enantio-selective allylic substitutions with carbon nucleophiles have been highlighted. 

Excellent stereoselectivities can be observed in Favorskii rearrangements. In the ring contraction of cyclohexanone 17, cyclopentane 18 was observed with greater than 10 1 dr, which prompted the authors to study a series of related compounds to determine the factors that control the stereoselectivity. Of compounds 19, 20, and 21, only 19 underwent a Favorskii rearrangement, also with high diastereoselectivity, leading the authors to conclude that a 3-oxy substituent is critical to the success of the rearrangement. ... 

Three steps transform (5)-carvone 7 into the a-chloro-cyclohexanone derivative 8. The Favorskii rearrangement on this substrate leads stereoselectively to the highly... 

The stereoselectivity of the Favorskii rearrangement described above can be explained by the mechanism of the reaction, as shown in Scheme 18.4. The ring opening of the cyclopropane ring of 16 could a priori occur by two possible routes (a or b). Less substituted carbanions are more stable. However, in such a case, the more substituted carbanion 18 is favored (path b) because of the presence of the electron-withdrawing oxygen substituent. 

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