Regioselective Synthesis of 4‐(Arylsulfanyl)‐2‐hydroxyhomophthalates by [4+2] Cycloaddition of 3‐(Arylsulfanyl)‐1‐(trimethylsilyloxy)buta‐1,3‐dienes with Dimethyl Penta‐2,3‐dienedioate

Abstract

The [4 þ 2] cycloaddition of 3-(arylsulfanyl)-1-(trimethylsilyloxy)buta-1,3-dienes with dimethyl penta-2,3-dienedioate provides a convenient and regioselective approach to a variety of 4-(arylsulfanyl)-2-hydroxyhomophthalates. . This methodology was successfully applied to the synthesis of an analogue of lactonamycin [6], of the N 7 -C 25 fragment of psymberin [7], and of the 4-acetylisocoumarins AGI-7 and sescandelin [8]. Herein, we report what are, to the best of our knowledge, the first [4 þ 2] cycloadditions of 3-(arylsulfanyl)-1-(trimethylsilyloxy)buta-1,3-dienes with dimethyl penta-2,3-dienedioate. These reactions provide a convenient and regioselective approach to a variety of 4-(arylsulfanyl)-2-hydroxyhomophthalates which can be regarded as highly functionalized diaryl sulfides.Diaryl sulfides are of considerable pharmacological relevance and occur in several natural products. Examples include the lissoclibadins, dibenzothiophenes, cyclic sulfides, varacins (lissoclinotoxins), and related natural products [9]. Diaryl sulfides are available by reaction of arenes with sulfur 1 ) or sulfur dichloride [11], by condensation of organometallic reagents with chlorophenylsulfides [12] or by basemediated reactions of thiophenols with chloroarenes [13]. However, the competing formation of polysulfides and, in several cases, the low regioselectivities are severe