Stereoselective Synthesis of cis‐2,6‐Disubstituted Morpholines and 1,4‐Oxathianes by Intramolecular Reductive Etherification of 1,5‐Diketones

Abstract

A simple and efficient, Lewis acid catalysed reductive etherification strategy for the stereoselective synthesis of cis‐2,6‐disubstituted morpholines and 1,4‐oxathianes starting from readily available 1,5‐diketones has been developed. The strategy is used in the total synthesis of morpholine‐based natural products (±)‐chelonin A and formal total synthesis of (±)‐chelonin C.

Recent Functionalizations of Primary Sulfonamides

“…where the sulfonyl group sits outside of the ring -are employed as amine protecting groups, 49,144 while there are just a few endocyclic examples, where the sulfur atom forms part of the ring. 131,197 However, the scope for the sulfonamide moiety being installed in a ring, and especially in a macrocycle, is still broad and underexplored, even though macrocycles have seen a resurgence in popularity in drug discovery.…”

Selective access to sulfurated and selenated heterocycles by intramolecular cyclization of β-substituted sulfides and selenides

“…Among the various heterocyclic compounds, six-membered 1,4-heterocycles have attracted considerable attention for their properties in medicinal and biological field, and for their use in organic synthesis 2 . 1,4-Oxathiane derivatives possess for instance antitumor 3 , antibacterial 4 and antifungal activity 2a , and find application as chiral auxiliaries for asymmetric transformations 5 . Replacement of oxygen with sulfur in thiomorpholines allows to obtain compounds with antioxidant and hypolipidemic activity 6 , and to access derivatives that can behave as DPP-IV inhibitors 7 .…”

Iron-Catalyzed Synthesis of Sulfur-Containing Heterocycles

“…As a consequence, a large range of synthetic methods has been developed to access these S -containing heterocycles. In particular, 1,4-oxathianes could variously be prepared using a Mitsunobu reaction, a ring expansion, a reductive etherification or by functionalization of hydroxythiols. , However, few of the reported methods are based on the use of catalytic quantities of reagent to mediate the formation of these S -containing heterocycles. Nowadays, there is a growing need to develop nonexpensive, eco-friendly and powerful synthetic methods that could be turned into industrial processes.…”