A Stereoselective One-Pot Synthetic Approach to Functionalized Thietanes

Abstract

A facile synthetic route to functionalized thietanes has been developed by employing one-pot, high-yielding, and highly diastereoselective three-component coupling reaction of O,O-diethyl hydrogen phosphorodithioate, aromatic aldehydes, and activated olefins. The synthesis involves Michael addition of the dithioate to acrylonitrile/methyl acrylate followed by addition of the resulting carbanion to an aldehyde and intramolecular cyclization to afford 2-arylthietane-3-carbonitriles/carboxylates at room temperature.

Recent synthesis of thietanes

“…Yadav and co-worker first realized the synthesis of functionalized thietanes 478 from O,O-diethyl hydrogen phosphorodithioate (463), aromatic aldehydes 476, and electron-deficient olefins (acrylonitrile (187b) and methyl acrylate (187c)). They first conducted a Baylis-Hillman reaction to prepare the Baylis-Hillman adducts 477 of aromatic aldehydes 476 with acrylonitrile (187b) and methyl acrylate (187c), and then cyclized the adducts 477 with O,O-diethyl hydrogen phosphorodithioate (463) in the presence of two equivalents of sodium hydride to afford the functionalized thietanes 478 [141] (Scheme 109). To make the strategy more efficient, the same group developed a one-pot protocol.…”

“…To make the strategy more efficient, the same group developed a one-pot protocol. The one-pot three-component coupling reaction of O,O-diethyl hydrogen phosphorodithioate (463), aromatic aldehydes 476, and electron-deficient olefins 187b,c proofed as efficient method for the highly diastereoselective synthesis of functionalized thietanes 478 in high yields [141] (Scheme 110).…”

“…The latter attacked aldehydes 476 to give the alkoxide anions 481 that underwent an intramolecular addition and elimination to generate thiolates 483. The thiolates then afforded the desired thietane products 478 after intramolecular substitution [141] (Scheme 111).…”

Anionic Cascade Routes to Sulfur and Nitrogen Heterocycles Originating from Thio‐ and Aminophosphate Precursors

“…Yadav has designed two routes to 2,3-substituted thietanes inspired by the Baylis-Hillman reaction (Scheme 16). [30] The first route utilizes modified Baylis-Hillman reaction conditions [31] to afford the classic adduct, which is then reacted with dithiophosphoric acid ester in the presence of sodium hydride to afford the desired thietane in the second step. Not satisfied, he developed a one-pot synthesis, which is triggered by initial dithiophosphate Michael-addition step, followed by trapping of the resulting stabilized carbanion with an aryl aldehyde, which then triggers the phosphate mediated cascade to form the thietane product.…”

Heterocyclic chemistry

“…13 The process relies upon the treatment of diethyl phosphorodithioate with sodium hydride, addition of the resulting anion to the Michael acceptor and subsequent reaction with an aldehyde to afford the thietane. At the very end of 2009, the formation of highly strained 1,2-diazetidines (see Scheme 14) was reported.…”