Mizhi Xu, McKinley K. Paul, Krista K. Bullard, Christopher DuPre, Will R. Gutekunst*
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引用次数: 1
Abstract
The unusual reactivity of twisted amides has long been associated with the degree of amide distortion, though classical bridged bicyclic amides offer limited methods to further modify these parameters. Here, we report that the geometry and reactivity of a single twisted amide scaffold can be significantly modulated through remote substituent effects. Guided by calculated ground state geometries, a library of twisted amide derivatives was efficiently prepared through a divergent synthetic strategy. Kinetic and mechanistic investigations of these amides in the alkylation/halide-rebound ring-opening reaction with alkyl halides show a strong positive correlation between the electron donating ability of the substituent and distortion of the amide bond, leading to rates of nucleophilic substitution spanning nearly 2 orders of magnitude. The rate limiting step of the cascade sequence is found to be dependent on the nature of the substituent, and additional studies highlight the role of solvent polarity and halide ion on reaction pathway and efficiency.
期刊介绍:
The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.