Organocatalytic Asymmetric Synthesis of Tetrahydrothiophenes and Tetrahydrothiopyrans

Abstract

Tetrahydrothiophenes and tetrahydrothiopyrans are an important class of compounds both from synthetic and biological points of view and have attracted the attention of many synthetic chemists and biologists over the years. Their high synthetic utility and diverse distribution in nature have made tetrahydrothiophenes and tetrahydrothiopyrans privileged motifs in organic chemistry. The last decade has witnessed great exploration of organocatalytic domino methods for the synthesis of enantiopure tetrahydrothiophenes and tetrahydrothiopyrans containing multiple stereocentres. The application of new bidentate reagents containing sulfur moieties in the development of double Michael reactions has revolutionized their synthesis. This microreview highlights recent organocatalytic asymmetric approaches to the synthesis of tetrahydrothiophenes and tetrahydrothiopyrans and describes the advances that have been made over the years.

A General Approach to Various Five‐ and Six‐Membered gem‐Difluoroheterocycles: Application to the Synthesis of Fluorinated Analogues of Sedamine

“…They play a vital role in the metabolism of living cells and they are present in a wide variety of drugs, natural products, and biologically important compounds , . The five‐ and six‐membered O ‐, S ‐ and N ‐containing heterocycles such as tetrahydrofurans, tetrahydropyrans and their sulfur analogues, as well as pyrrolidines and piperidines, are at the core of numerous bioactive natural products and drugs. Thus, many elegant synthetic methods have been developed toward corresponding heterocycles.…”

“…Cyclic ethers (THP and THF rings), represent important synthetic targets owing to their structures and the biological properties of corresponding molecules, including immunosuppressant, antitumor, antiulcer, antiproliferative, antiparasitic, and anti‐inflammatory activities . The diospongin B, with antiosteoporotic activity, is a representative example of this class of products (Figure ) .…”

1,4‐Dithiane‐2,5‐diol: An Attractive Platform for the Synthesis of Sulfur‐Containing Functionalized Heterocycles

“…A recent review highlighted the versatility of spiro scaffolds in drug discovery, owing to their inherent threedimensionality and structural novelty. [23] The main structures synthesized are listed in Scheme 16. A variety of spirotetrahydrothiophene scaffolds anchored to different skeletons have been described in a flurry of papers appearing in the literature over the last four years, [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] taking advantage of the excellent anellating properties both of 1 and of the derived 4-mercaptobut-2-enoates 11a-d in partnership with α,unsaturated carbonyl compounds.…”

“…These transformations have been reviewed very recently, highlighting the pivotal role of organocatalysis as a powerful and versatile tool for the rapid construction of spirotetrahydrothiophene motifs. [23] The main structures synthesized are listed in Scheme 16.…”

Six-Membered Ring Systems: With O and/or S Atoms

“…Reviews on stereoselective organocatalytic synthesis of tetrahydropyrans (17EJO4666), of tetrahydropyrans and their application in total synthesis of natural products (17CSR1661), on the synthesis of the less thermodynamically stable 2,6-trans-tetrahydropyrans (17S4899), on enantioselective synthesis of polyfunctionalized pyran and chromene derivatives (17TA1462), and on enantioselective and racemic total synthesis of camptothecins, including the formation of their pyran-2-one ring (17SL1134), have appeared.…”