In this study, mechanism and stereochemistry of multicomponent domino Knoevenagel/Diels–Alder reaction were investigated theoretically. Structures of reagents, transition states, intermediates, and products were optimized at M062X/6-31[Formula: see text]G(d,p) level of theory. Although the mechanism of this reaction involved several processes, including bond rotation, isomerization, asymmetric cycloaddition, acid-base, and nucleophile–electrophile competitions, critical processes were studied to provide a clearer picture of the mechanism of this valuable reaction in terms of stereochemistry considerations. According to the results, the ring closure step of reaction performed via a polar Dield-Alder mechanism, having enthalpy at approximately 40[Formula: see text]kcal/mol. The diastereoselectivity of the reaction was controlled by the interaction of dienophile with the less hindered face of diene through a more stable endo transition state ([Formula: see text] and 27.31 in methanol and gas phase, respectively). HSAB criteria could explain the regioselectivity of this reaction by considering the least softness difference ([Formula: see text]) for interacting C-atoms based on Hirshfeld populations. The result was the creation of cis-spiro cyclohexanone under kinetic and thermodynamic controls as a predominant diastereoselective and regioselective product.
A novel, efficient one-pot approach for the synthesis of furopyrimidine and oxobenzofuran derivatives 4 by a multicomponent reaction of an isocyanide, an aldehyde, and a CH-acid compound in CH 2 Cl 2 is reported (Scheme 1 and Table). The reactions were completed after 20 h at room temperature. This method has the advantages of high yields, simple methodology, and easy workup.Introduction. -The synthetic routes to furopyrimidine and oxobenzofuran derivatives is not large, and only few procedures have been reported for the synthesis of furopyrimidines [1 -4], mostly relying on multi-step reactions giving low yields [1 -3]. These compounds are an important structural unit in natural products and are intermediates in drugs and organic synthesis [5] [6]. As part of our continuing interest in the development of new synthetic methods in heterocyclic chemistry and the recent interest in isocyanide-based multicomponent reactions [7 -10], we now describe an efficient synthesis of furopyrimidine and oxobenzofuran derivatives via the reaction of CH-acids with aldehydes and isocyanides in CH 2 Cl 2 at room temperature.
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