Computational Insight to Stereochemical Control on Conjugate Addition of Pyrroloalkenyl Thiol on Activated Alkyne

ABSTRACT [3+2] Cycloaddition reaction of thiazolium ylide with activated acetylene does not yield the expected pyrrolothiazole, in contrast to a similar reaction of other N ‐cycloiminium ylides. Initially formed [3+2] cycloadduct undergoes thiazole ring opening followed by a thiol‐yne type nucleophilic addition on second molecule of activated alkyne to give E , Z and/or Z , Z isomers of 1:2 adduct. We have investigated the reaction of thiazolium ylides with alkyl propiolate computationally at DFT level to understand the impact of stereochemical control on mechanistic aspects. Relatively more stable conformer of thiazolium ylide leads to a thermodynamically as well as kinetically preferred diastereomer of the cycloadduct having trans orientation of hydrogen atoms, which restricts the auto‐oxidation and facilitates the ring opening. Formation of the Z or E isomer in subsequent thiol‐yne reaction depends on the stereochemical control of the allene or allenoate intermediate. Experimentally observed reactivity of thiazolium ylide is computationally rationalized on the basis of the CDFT‐based reactivity indices and the stereochemical control on reaction mechanism.