Systematic Evaluation of 1,2-Migratory Aptitude in Alkylidene Carbenes

Abstract

Alkylidene carbenes undergo rapid inter-and intra-molecular reactions and rearrangements, including 1,2-migrations of β-substituents to generate alkynes. Their propensity for substituent migration exerts profound influence over the broader utility of alkylidene carbene intermediates, yet prior efforts to categorize 1,2-migratory aptitude in these elusive species have been hampered by disparate modes of carbene generation, ultrashort carbene lifetimes, mechanistic ambiguities, and the need to individually prepare a series of 13 C-labelled precursors. Herein we report on the rearrangement of 13 C-alkylidene carbenes generated in situ by the homologation of carbonyl compounds with [ 13 C]-Li-TMS-diazomethane, an approach that obviates the need for isotopically labelled substrates and has expedited a systematic investigation ( 13 C{ 1 H} NMR, DLPNO-CCSD(T)) of migratory aptitudes in an unprecedented range of more than 30 alkylidene carbenes. Hammett analyses of the reactions of 26 differentially substituted benzophenones reveal several counterintuitive features of 1,2-migration in alkylidene carbenes that may prove of utility in the study and synthetic application of unsaturated carbenes more generally.

Stereoelectronic Features of a Complex Ketene Dimerization Reaction

“…The structure is assigned to 26 based on its mass, H-1 and C-13 spectra, and by comparison to reference compounds in the literature. In particular, the new ring methine H-3 (in red) is shifted downfield (7.17 ppm; compare 7.20 ppm reported for the closely related N-methyl analogue [20]) relative to a possible isomeric structure with thienyl at C-3 (27). The latter compound (H-4, in red, expected at 6.6 ppm [21]), which would have resulted from a C-3 to C-4 hydride shift, was not detected in the reaction of 2.…”

“…In the case of 5 , room-temperature loss of CO may be driven by the stability of the resulting through-conjugated carbene 25 . Carbene insertion into the C-C bond of adjacent electron-rich aryl substituents has been previously reported, as has vicinal 2-thienyl migration in a gold–carbene intermediate [ 27 , 28 ].…”

Stopped‐Flow 19F NMR Spectroscopic Analysis of a Protodeboronation Proceeding at the Sub‐Second Time‐Scale

“…[15,16] However, monitoring rapid irreversible reactions by NMR spectroscopy poses a considerably different challenge, especially when such processes are initiated by mixing, rather than by a readily controlled external stimulus such as light. [17] Over the last decade we have investigated a wide range of anion-mediated processes involving organoboron [18][19][20][21] and organosilicon [22][23][24][25][26] reagents, including hydrolytic activation and degradation of boronic acids, [18,21] and their derivatives. [19,20] In the majority of examples we were able to employ standard 1 H, 11 B, 19 F, and 29 Si NMR spectroscopic techniques to analyze the reaction kinetics.…”

“…Over the last decade we have investigated a wide range of anion‐mediated processes involving organoboron [18–21] and organosilicon [22–26] reagents, including hydrolytic activation and degradation of boronic acids, [18,21] and their derivatives [19,20] . In the majority of examples we were able to employ standard 1 H, 11 B, 19 F, and 29 Si NMR spectroscopic techniques to analyze the reaction kinetics.…”

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

“…The substrate scope results suggest that aryl and alkynyl groups are migratable, whereas alkyl groups are not. The FBW rearrangement of magnesium alkylidene carbenoids seems to be an anionotropic rearrangement because the trend of migratory aptitude (aryl, alkynyl >> alkyl) follows the trend of the stability of carbanions [ 21 – 22 ]. The trans -relationship between the chloro group and the migrating substituent appears to be of importance for a successful 1,2-rearrangement [ 8 ].…”