Favorskii rearrangements. IX. Stereochemistry of the reaction with 2-bromo-4-methyl-4-phenylcyclohexanone

Abstract

In the reaction of 2-chlorocyclohexanone or 2-bromo-~5-methyl-5-phenylcyclohexanone (cis or trans) with NaOMe in MeOH the yield of Favorskii ester has been found to increase markedly at the expense of or-methoxyoxirane and or-methoxy ketone products on increasing the methoxide concentration. 2-Chloro-and 2-bromo-4methyl-4-phenylcyclohexanones ( 6 ) are much less subject to this concentration effect, 407, yield of Favorskii ester being obtained even at low (-10-5 M ) methoxide concentrations. The ratio of stereoisomeric esters formed from 6 was found to be reversed in going from low to high (2 M ) methoxide concentrations. This result i3 rationalized in terms of equilibrating dipolar ion and cyclopropanone intermediates.

A convenient preparation of 3-isopropyl-1-methylcyclopentylmethanol and 1-isopropyl-3-methylcyclopentylmethanol via Favorskii rearrangement

“…These findings strongly suggest a Favorskii rearrangement occurring through a mechanism entailing on the formation of an intermediate cyclopropanone via an S N the alternative mechanism via a zwitterionic intermediate, 19 the latter requiring that both haloketones 6 and 7 produce the same mixture of esters 8 and 9.…”

Stereochemically Probing the Photo-Favorskii Rearrangement: A Mechanistic Investigation

“…10 Instead, the complete racemization of pHP analogs involves an oxyallyl-phenoxy intermediate paralleling the ground state mechanism of Dewar 14 and documented by Bordwell. 12,17 Alternative routes, e.g., equilibration of the starting esters or a concerted formation of p -hydroxybenzyl acylium intermediates, 6h do not occur.…”

“…8 Rrelevant examples are studies of the stereochemistry of the ground state Favorskii rearrangement extensively examined by House, 9 Sorenson, 10 Bernetti, 11 and by Bordwell. 12 The seminal studies by Loftfield 13 on the 1,2-carbon migration later challenged by Dewar’s theoretical treatment 14 now serve as the two limiting mechanisms for the base-promoted Favorskii rearrangement. Loftfield’s one-step concerted S N 2 process contrasts with Dewar‘s two-step preformation of an oxyallyl zwitterion intermediate prior to cyclization by disrotatory closure 15 to generate the Favorskii cyclopropanone intermediate.…”

Catalyst-free formation of 1,4-diketones by addition of silyl enolates to oxyallyl zwitterions in situ generated from α-haloketones

“…19 Furthermore, the oxyallyl zwitterions have also been known as dienophiles in [4 + 3] cycloadditions to construct seven-membered carbocycles across a wide range of unique applications. Under typical Favorskii rearrangement conditions (Scheme 3), 21 strong bases induce the formation of cyclopentanone intermediates XV from a-haloketones and then the ring-contracted product XVII, 22 XVIII,23 or XIX 24 is produced depending on the p-nucleophile we used. Under typical Favorskii rearrangement conditions (Scheme 3), 21 strong bases induce the formation of cyclopentanone intermediates XV from a-haloketones and then the ring-contracted product XVII, 22 XVIII,23 or XIX 24 is produced depending on the p-nucleophile we used.…”

“…20 To shed light on the reaction mechanism of nucleophiles with oxyallyls (cyclopentanone intermediates and oxyallyl zwitterions), different types of reactions are summarized in Scheme 3 and 4. Under typical Favorskii rearrangement conditions (Scheme 3), 21 strong bases induce the formation of cyclopentanone intermediates XV from a-haloketones and then the ring-contracted product XVII, 22 XVIII, 23 or XIX 24 is produced depending on the p-nucleophile we used. Remarkably, treatment of 2-chlorocyclopentanone with the weak base (sodium carbonate) instead of the strong base (sodium hydroxide) affords an excellent yield of the substituted product XX.…”