Thiopyrans and Fused Thiopyrans

2.25 Thiopyrans and Fused Thiopyrans A. H. INGALL Fison's Pharmaceuticals Ltd., Loughborough 2.25.1 INTRODUCTION 2.25.2 STRUCTURE OF THIOPYRANS 2.25.2.1 Structure of Tetrahydrothiopyrans 2.25.2.2 Structure of Dihydrothiopyrans 2.25.2.3 Structure of 2H- and 4H-Thiopyrans 2.25.2.4 Structure of Thiopyrylium Salts 2.25.2.5 Structure of lH-Thiopyrans 2.25.3 REACTIVITY OF THIOPYRANS 2.25.3.1 Reactivity of Tetrahydrothiopyrans 2.25.3.2 Reactivity of Dihydrothiopyrans 2.25.3.3 Reactivity of 2H- and 4H-Thiopyrans 2.25.3.4 Reactivity of Thiopyrylium Salts 2.25.3.5 Reactivity of Thiabenzenes 2.25.4 SYNTHESIS OF THIOPYRANS 2.25.4.1 Synthesis of Tetrahydrothiopyrans 2.25.4.1.1 De novo ring synthesis 2.25.4.1.2 Ring transformations leading to thianes 2.25.4.1.3 Synthesis of thiane derivatives 2.25.4.2 Synthesis of Dihydrothiopyrans 2.25.4.2.1 De novo ring synthesis 2.25.4.2.2 Ring transformations leading to dihydrothiopyrans 2.25.4.2.3 Synthesis of dihydrothiopyran derivatives 2.25.4.3 Synthesis of 2H- and 4H-Thiopyrans 2.25.4.3.1 De novo ring synthesis 2.25.4.3.2 Ring transformations leading to thiopyrans 2.25.4.3.3 Synthesis of thiopyran derivatives 2.25.4.4 Synthesis of Thiopyrylium Salts 2.25.4.4.1 De novo ring synthesis 2.25.4.4.2 Ring transformations leading to thiopyrylium salts 2.25.4.4.3 Synthesis of thiopyrylium derivatives 2.25.4.5 Synthesis of Thiabenzenes 2.25.5 APPLICATIONS OF THIOPYRANS

885 887 887 891 891 893 893 895 895 903 911 922 925 926 927 927 928 928 929 929 933 933 934 934 935 937 937 937 938 938 939 939

2.25.1 INTRODUCTION The nomenclature of the family of compounds to be discussed below has for long been the cause of much confusion. The systematic name for a six-membered ring containing one sulfur atom is thiin, but Chemical Abstracts uses the name thiopyran, while many earlier publications have used the 'replacement nomenclature' thiapyran (which is strictly inaccurate as 'thia' implies replacement of carbon, rather than oxygen, by sulfur). Throughout this chapter the terms thiopyran and thiin will be used interchangeably, while 'thiadecalin' nomenclature will be found convenient for the perhydrobenzothiopyran systems. Whereas the chemistry of pyrans is an immense body of knowledge, that of thiopyrans has been less extensively investigated; this is probably a reflection of the widespread availability of diverse six-membered oxygen heterocycles and their congeners in Nature vis-d-vis the almost total non-existence of naturally occurring sulfur-containing analogues. Apart from a small number of compounds found in crude oil, all thiopyrans are only 885