Telescoped, Divergent, Chemoselective C1 and C1‐C1 Homologation of Imine Surrogates: Access to Quaternary Chloro‐ and Halomethyl‐Trifluoromethyl Aziridines

Abstract

A conceptually novel, high‐yielding, mono‐ or bis‐homologation was realized with lithium halocarbenoids and enables the one‐step, fully chemocontrolled assembly of a new class of quaternary trifluoromethyl aziridines. Trifluoroacetimidoyl chlorides (TFAICs) act as convenient electrophilic platforms, enabling the addition of either one or two homologating elements by simply controlling the stoichiometry of the process. Mechanistic studies highlighted that the homologation event, carried out with two different carbenoids (LiCH 2 Cl and LiCH 2 F), leads to fluoromethyl analogues in which the first nucleophile is employed for constructing the cycle and the second for decorating the resulting molecular architecture.

Modular and Chemoselective Strategy for Accessing (Distinct) α,α‐Dihaloketones from Weinreb Amides and Dihalomethyllithiums

“…[31] Upon preformation of the base, it was added to the mixture of Weinreb amide and BrCH 2 Cl through a syringe pump (0.2 mL/min rate). [32] [a] The ratio has been determined by 1 H-NMR analysis using 1,3,5-trimethylbenzene as an internal standard. [b] Isolated yield after purification.…”

“…permitted the double functionalization of a 1,4-bis Weinreb amide, giving the tetrachlorinated ketone 27. Heteroaromatic [2thienyl (28) and 2-furanyl (29)], as well as, α,βunsaturated (30)(31) or fully saturated systems (32) could also be efficiently prepared under full chemocontrol (i. e. no modification of olefin in 30-31, [34] integrity of C Ar -Br bond in 31).…”

Weinreb Amides as Privileged Acylating Agents for Accessing α-Substituted Ketones

“…Weinreb amides represent excellent acylating agents for -substituted organometallic reagents and the concomitant presence of additional reactive sites usually does not impede selective transformations, thus targeting the nucleophile towards the amide (Scheme 21). However, highly electrophilic functionalities such as the ketones of isatins 61 or trifluoroacetimidoyl chlorides 62 alter this behavior and, accordingly, halomethyllithiums react exclusively at those positions generating interesting structures such as spiroepoxyoxyindoles or a quaternary trifluoromethyl-aziridine decorated with a pendant Weinreb amide. As a consequence, late manipulations of this fragment offer the possibility to further increase the final molecular complexity.…”

Consecutive C1‐Homologation / Displacement Strategy for Converting Thiosulfonates into O,S‐Oxothioacetals

“…[8] Motivated by the interest towards such chemistry, we designed selective processes characterized by the triggering of molecular rearrangements once the initial homologation was accomplished, e. g. fully α-substituted aldehydes from vinyl ketones [9] or, aziridines via telescoped homologations of TFAICs. [10] To the best of our knowledge, classical manifolds for conducting the C1-insertions have been restricted to XÀ Y systems (X, Y = carbon-carbon, carbon-heteroatom, heteroatom 1heteroatom 2) [11] whereas, analogous operations on homo-dimeric materials (XÀ X, X = heteroatom) are much less developed. In this context, in 2016 we reported a direct procedure for converting disulfides and diselenides into symmetrical dithioacetals and diselenoacetals, respectively (Scheme 1c).…”