In-Cage\nRecombination Facilitates the Enantioselective\nOrganocatalytic [1,2]-Rearrangement of Allylic Ammonium Ylides

The [1,2]-rearrangement\nof allylic ammonium ylides is traditionally\nobserved as a competitive minor pathway alongside the thermally allowed\n[2,3]-sigmatropic rearrangement. Concerted [1,2]-rearrangements are\nformally forbidden, with these processes believed to proceed through\nhomolytic C–N bond fission of the ylide, followed by radical–radical\nrecombination. The challenges associated with developing a catalytic\nenantioselective [1,2]-rearrangement of allylic ammonium ylides therefore\nlie in biasing the reaction pathway to favor the [1,2]-reaction product,\nalongside controlling a stereoselective radical–radical recombination\nevent. Herein, a Lewis basic chiral isothiourea facilitates catalytic\n[1,2]-rearrangement of prochiral aryl ester ammonium salts to generate\nunnatural α-amino acid derivatives with up to complete selectivity\nover the [2,3]-rearrangement and with good to excellent enantiocontrol.\nKey factors in favoring the [1,2]-rearrangement include exploitation\nof disubstituted terminal allylic substituents, cyclic N-substituted\nammonium salts, and elevated reaction temperatures. Mechanistic studies\ninvolving <sup>13</sup>C-labeling and crossover reactions, combined\nwith radical trapping experiments and observed changes in product\nenantioselectivity, are consistent with a radical solvent cage effect,\nwith maximum product enantioselectivity observed through promotion\nof “in-cage” radical–radical recombination. Computational\nanalysis indicates that the distribution between [1,2]- and [2,3]-rearrangement\nproducts arises predominantly from C–N bond homolysis of an\nintermediate ammonium ylide, followed by recombination of the α-amino\nradical at either the primary or tertiary site of an intermediate\nallylic radical. Electrostatic interactions involving the bromide\ncounterion control the facial selectivity of the [1,2]- and [2,3]-rearrangements,\nwhile the sterically hindered tertiary position of the allylic substituent\ndisfavors the formation of the [2,3]-product. These results will impact\nfurther investigations and understanding of enantioselective radical–radical\nreactions.