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. 2024 Apr 19;89(8):5911-5916.
doi: 10.1021/acs.joc.4c00604. Epub 2024 Apr 10.

The Development of a Sulfamate-Tethered Aza-Michael Cyclization Allows for the Preparation of (-)-Negamycin tert-Butyl Ester

Harshit Joshi  1 , Appasaheb K Nirpal  1 , Debobrata Paul  1 , Steven P Kelley  2 , Joel T Mague  3 , Shyam Sathyamoorthi  1
Affiliations

The Development of a Sulfamate-Tethered Aza-Michael Cyclization Allows for the Preparation of (-)-Negamycin tert-Butyl Ester

Harshit Joshi et al. J Org Chem. .

Abstract

We present the first examples of intramolecular aza-Michael cyclizations of sulfamates and sulfamides onto pendant α,β-unsaturated esters, thioesters, amides, and nitriles. Stirring the substrate with catalytic quantities of the appropriate base delivers the product in good yield and excellent diastereoselectivity. The reactions are operationally simple, can be performed open to air, and are tolerant of a variety of important functional groups. We highlight the utility of this technology by using it in the preparation of a (-)-negamycin derivative.

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Figures

Scheme 1.
Scheme 1.
A robust sulfamate-tethered aza-Michael cyclization would supply highly valuable synthetic intermediates.
Scheme 2.
Scheme 2.
Structure-Reactivity Relationship with Diverse Sulfamate Esters.
Scheme 3.
Scheme 3.
Exploring Reactivity with Diverse Michael Acceptors.
Scheme 4.
Scheme 4.
Using a menthol ester allows for the synthesis of chiral oxathiazinanes
Scheme 5.
Scheme 5.
Assessing Functional Group Compatibility and Diastereoselectivity.
Scheme 6.
Scheme 6.
Synthesis of a protected (−)-negamycin.
See this image and copyright information in PMC

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