Studies toward Gymnodimine:  Development of a Single-Pot Hua Reaction for the Synthesis of Highly Hindered Cyclic Imines

Abstract

[structure: see text]. In studies directed toward gymnodimine and related marine toxins, a single-pot variation of the Hua cyclic imine synthesis has been developed. The reaction involves generation of N-trimethylsilyl lactams in situ followed by alkyllithium addition leading directly to cyclic imines. Importantly, this reaction proceeds efficiently with highly hindered alpha,alpha-dialkyl lactams, provided 1,2-dimethoxyethane (DME) is used as solvent, leading to stable cyclic imines. Overall, this transformation allows a one-pot coupling of an alkyliodide and a lactam to give a cyclic imine.

An Autoimmolative Spacer Allows First‐Time Incorporation of a Unique Solid‐State Fluorophore into a Detection Probe for Acyl Hydrolases

“…This gave 8 in low yield, the hydrogenation of which necessitated the use of 10 % Pd/C, but then gave 1 in quantitative yield in 2 h. Target 2, containing two methyl groups on the a carbon of the linker, required us to exhaustively methylate pyrrolidin-2-one according to a literature procedure (Scheme 1). [36] The resulting a,a-dimethyl-g-lactam can be opened by heating in concentrated hydrochloric acid. The strong tendency of this GABA derivative to recyclize makes a special procedure necessary, that is, the activation of Cbz-Leucine as a succinate ester and its smooth conversion with the obtained hydrochloride in the presence of triethylamine to give the free acid 5 in 57 % yield.…”

Product Class 7: Imines

“…[189] A single-pot variation has been developed in which N-(trimethylsilyl) lactams are generated in situ by silylation with trimethylsilyl trifluoromethanesulfonate, followed by alkyllithium addition, thus leading to stable cyclic ketimines 39 (Scheme 18). [190] The use of 1,2-dimethoxyethane as solvent seems crucial here, since no alkylation is observed in other solvents.…”

Lactamomethylsilanes – Synthesis, Structures, and Reactivity towards CO2 and Phenylisocyanate

“…Lactames are common structural motifs in the synthesis of polyamide 6 from ε‐caprolactam or β‐lactam antibiotics. As state of the art, a trialkylsilyl moiety is attached to the lactam nitrogen atom as protecting group to metallate the α‐carbon for further reactions . Silylated lactames can react with organic acid chlorides, phosphorchlorides or methanal to form an N–C bond , .…”

“…Silylated lactames can react with organic acid chlorides, phosphorchlorides or methanal to form an N–C bond , . With strong nucleopilic bases, such as lithium organyls, imines can be synthesized starting with silylated lactams , . The silylation of ε‐caprolactam and afterwards the polymerization leads to new inorganic‐organic hybrid materials …”