A Photo-Favorskii Ring Contraction Reaction: The Effect of Ring Size

Abstract

The effect of ring size on the photo-Favorskii induced ring-contraction reaction of the hydroxybenzocycloalkanonyl acetate and mesylate esters (7a–d, 8a–c) has provided new insight into the mechanism of the rearrangement. By monotonically decreasing the ring size in these cyclic derivatives, the increasing ring strain imposed on the formation of the elusive bicyclic spirocyclopropanone 20 results in a divergence away from rearrangement and toward solvolysis. Cycloalkanones of seven or eight carbons undergo a highly efficient photo-Favorskii rearrangement with ring contraction paralleling the photochemistry of p-hydroxyphenacyl esters. In contrast, the five-carbon ring does not rearrange but is diverted to the photosolvolysis channel avoiding the increased strain energy that would accompany the formation of the spirobicyclic ketone, the “Favorskii intermediate 20”. The six-carbon analogue demonstrates the bifurcation in reaction channels, yielding a solvent-sensitive mixture of both. Employing a combination of time-resolved absorption measurements, quantum yield determinations, isotopic labeling, and solvent variation studies coupled with theoretical treatment, a more comprehensive mechanistic description of the rearrangement has emerged.

Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy

“…Recently, the effect of ring size on the photo-Favorskii-induced ring-contraction reaction of various hydroxybenzocycloalkanonyl acetate and mesylate esters has provided new insight into the mechanism of the rearrangement. 98 …”

“…104 The rearrangement proceeds from the chromophore’s triplet excited state ( 3 24 ) by a concerted departure of the leaving group and the phenolic proton generating the triplet biradical 3 28 . Intersystem crossing of 3 28 gives an intermediate common to the ground state Favorskii rearrangement, 102a−102c the putative cyclopropanone, 86,98,102 that either hydrolyzes or decarbonylates on its pathway to the final products. The evidence provided, however, requires involvement of another intermediate, presumably the singlet allyloxy-phenoxy species 1 28 , 98,99,104b to account for the complete racemization of a p -hydroxypropiophenone analogue where the leaving group is affixed to a stereogenic α-carbon.…”

“…Intersystem crossing of 3 28 gives an intermediate common to the ground state Favorskii rearrangement, 102a−102c the putative cyclopropanone, 86,98,102 that either hydrolyzes or decarbonylates on its pathway to the final products. The evidence provided, however, requires involvement of another intermediate, presumably the singlet allyloxy-phenoxy species 1 28 , 98,99,104b to account for the complete racemization of a p -hydroxypropiophenone analogue where the leaving group is affixed to a stereogenic α-carbon. 104b This mechanism also provides a pathway for the minor photohydrolysis byproduct 24 (X = OH) that becomes predominant for the ring-contraction photoreactions of hydroxybenzocycloalkanonyl esters when ring strain discourages or prevents cyclopropanone formation.…”

“…104b This mechanism also provides a pathway for the minor photohydrolysis byproduct 24 (X = OH) that becomes predominant for the ring-contraction photoreactions of hydroxybenzocycloalkanonyl esters when ring strain discourages or prevents cyclopropanone formation. 98 …”

Iodine(III)-Mediated Ring Contraction Reactions: Synthesis of Oxygen- and Nitrogen-Substituted Indanes

“…3 Numerous synthetic methodologies have been developed to construct indane core including cyclization, [4][5][6] cycloaddition, [7][8][9] and rearrangements. [10][11][12][13] Indanes substituted in the aromatic ring by nitrogen [14][15][16][17][18] or by oxygen 2,[19][20][21][22] are present in compounds with promising biological activities. Hypervalent iodine reagents play a substantial role in chemical synthesis, promoting efficiently carbon-carbon bond formations, rearrangements and functional group interconversions, including asymmetric versions for many reactions.…”