Migratory Aptitudes in Rearrangements of Destabilized Vinyl Cations

Abstract

The Lewis acid-promoted generation of destabilized vinyl cations from β-hydroxy diazo ketones leads to an energetically favorable 1,2-shift across the alkene followed by an irreversible C–H insertion to give cyclopentenone products. This reaction sequence overcomes typical challenges of counter-ion trapping and rearrangement reversibility of vinyl cations and has been used to study the migratory aptitudes of nonequivalent substituents in an uncommon C­(sp2) to C­(sp) vinyl cation rearrangement. The migratory aptitude trends were consistent with those observed in other cationic rearrangements; the substituent that can best stabilize a cation more readily migrates. However, density functional theory calculations show that the situation is more complex. Selectivity in the formation of one conformational isomer of the vinyl cation and facial selective migration across the alkene due to an electrostatic interaction between the vinyl cation and the adjacent carbonyl oxygen work in concert to determine which group migrates. This study provides valuable insight into predicting migration preferences when applying this methodology to the synthesis of structurally complex cyclopentenones that are differentially substituted at the α and β positions.

Enantioselective Acyloin Rearrangement of Acyclic Aldehydes Catalyzed by Chiral Oxazaborolidinium Ion

“…The unreacted 1q was recovered in 35% yield with 99% ee ( s factor = 16) . These results matched well with the migration order for the pinacol rearrangement. ,, …”

Stereodivergent Alkyne Hydrofluorination Using a Simple Practical Reagent

“…A range of primary, secondary, cyclic or acyclic alkyl-substituted alkynes could be employed in the hydrofluorination to furnish respective products again with moderate to good yields and excellent regio-and stereoselectivities (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). Remarkably, substrates with potentially sensitive functional groups including a primary chloro, a carboxymethyl, a cyano, a pyridyl, and a phthalimido group also delivered the monofluoroalkene products, highlighting the mildness and good functional group tolerance of this protocol (40)(41)(42)(43)(44)(45)(46). This scalability of the procedure was demonstrated by the gram-scale preparation of 44, which proceeded with unchanged regio-and stereoselectivities and only a slightly reduced yield (1.65 g, 64%).…”

A Conjugate Addition Approach to Diazo‐Containing Scaffolds with β Quaternary Centers

“…2 ) as shown in Scheme . As part of our studies into the mechanism of the vinyl cation C−H insertion reaction, we modeled the reaction pathway computationally, which showed that the Lewis acid mediated dehydroxylation step was reversible, and that the rate limiting step of this sequence is formation of the vinyl cation by loss of N 2 from the vinyl diazonium intermediate. This led us to consider that it might be possible to intercept vinyl diazonium intermediate 2 with a nucleophile other than OH prior to N 2 dissociation to give a more complex product that still retains the diazo fragment.…”