Transition-Metal-Free Selective Halocyclization of N-Alkoxy Amides: Synthesis of N-Alkoxy Lactams and Oximinolactones

Sunil Dattatray Chakave; Venunath Hapse; Kishor Balkrishna Inamke; Amol Satish Dehade; Anupa Dessai; Mark Montgomery; Ravindra Punjaji Sonawane; Sandeep R. Kandukuri; Bhanu N. Manjunath

doi:10.1055/s-0042-1751574

Synthesis, Table of Contents

Synthesis 2024; 56(15): 2410-2422
DOI: 10.1055/s-0042-1751574

paper

Transition-Metal-Free Selective Halocyclization of N-Alkoxy Amides: Synthesis of N-Alkoxy Lactams and Oximinolactones

Sunil Dattatray Chakave

^aSyngenta Biosciences Pvt. Ltd., Santa Monica Works, Corlim, Ilhas, Goa-403110, India

^bDepartment of Chemistry, Mangalore University, Mangalagangothri, India 576119, India

,

Venunath Hapse

^aSyngenta Biosciences Pvt. Ltd., Santa Monica Works, Corlim, Ilhas, Goa-403110, India

,

Kishor Balkrishna Inamke

^aSyngenta Biosciences Pvt. Ltd., Santa Monica Works, Corlim, Ilhas, Goa-403110, India

,

Amol Satish Dehade

^aSyngenta Biosciences Pvt. Ltd., Santa Monica Works, Corlim, Ilhas, Goa-403110, India

,

Anupa Dessai

^aSyngenta Biosciences Pvt. Ltd., Santa Monica Works, Corlim, Ilhas, Goa-403110, India

,

Mark Montgomery

^cSyngenta Jealott’s Hill International Research Centre, Bracknell, RG42 6EY, UK

,

Ravindra Punjaji Sonawane

^dSyngenta Crop Protection AG, Schaffhauserstrasse, 4332 Stein, Switzerland

,

Sandeep R. Kandukuri∗

^aSyngenta Biosciences Pvt. Ltd., Santa Monica Works, Corlim, Ilhas, Goa-403110, India

,

Bhanu N. Manjunath∗

^aSyngenta Biosciences Pvt. Ltd., Santa Monica Works, Corlim, Ilhas, Goa-403110, India

^bDepartment of Chemistry, Mangalore University, Mangalagangothri, India 576119, India

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Abstract

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Abstract

A new method for the synthesis of N-alkoxy lactams and oximinolactones, involving the selective N-cyclization and O-cyclization of unsaturated N-alkoxy amides, is presented. This approach features mild reaction conditions and no requirement for transition-metal catalysts. The protocol demonstrates a wide range of applicability in 5-exo-trig and 6-exo-trig cyclization, accommodating chloro, bromo, and iodo electrophiles. The N-cyclization process can be achieved in the presence of strong lithium base such as LiHMDS or n-BuLi, while the O-cyclization occurs spontaneously without the addition of any base. Mechanistic studies reveal the N-cyclization reactions proceed through cyclic lithium intermediates, as confirmed by FT-IR studies and control experiments, which contribute to the N-selectivity. The current methodology was successfully used in synthesis of natural product (E/Z) des-hydroxy triticone A and B.

Key words

halocyclization - lactams - N-alkoxy amides - oximinolactones - triticone A and B

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Supplementary Material

Supporting Information