An Unexpected Phosphine‐Catalyzed Regio‐ and Diastereoselective [4+1] Annulation Reaction of Modified Allylic Compounds with Activated Enones

Abstract

Nucleophilic phosphines are known to be useful mild catalysts for the synthesis of cyclic and heterocyclic compounds. Generally, tertiary-phosphine-mediated annulations are triggered by nucleophilic addition of phosphines to activated compounds. The resultant zwitterionic intermediates can react with various electrophiles such as aldehydes, imines, and activated polarized C=C bonds to furnish cyclic compounds. Herein, we report a phosphine-catalyzed highly diastereoselective synthesis of tetrasubstituted 2,3-dihydrofurans, which are subunits of a range of biologically active compounds (e.g., aflatoxin B1 and clerodin), [4] via [4+1] annulations of Morita–Baylis–Hillman carbonates with activated enones. In these annulations, Morita–Baylis– Hillman carbonates act as the one-carbon unit, which is distinguished from the modified allylic compounds reported by Lu et al. as the three-carbon units, such as in [3+2], [3+3], [3+4], and [3+6] annulation reactions. In recent years, Morita–Baylis–Hillman adducts have been illustrated as suitable starting materials for the synthesis of a variety of multifunctional compounds. During our study of the new chemistry of electron-deficient enynes, we became interested in the annulation between Morita– Baylis–Hillman carbonate 1a and conjugated yne-enone 2a. We were pleased to find that the reaction proceeded smoothly in toluene at room temperature under catalysis with 10 mol% PPh3, leading to a [4+1] adduct, 2,3-dihydrofuran 3a, in 72% yield of isolated product with 20:1 diastereoselectivity (Table 1, entry 1). The structure of 3a was established by X-ray crystallography analysis of the analogous product 3f (R=p-BrC6H4; Figure 1). [7] To improve the yield of 3a, various solvents and tertiary phosphines were tested and the results are summarized in Table 1. A higher product yield was obtained when the reaction was performed in CH2Cl2, while the selectivity was slightly decreased (Table 1, entry 2). Good yields with high selectivity were also obtained in DCE, Et2O, and 1,4-dioxane, albeit the reactions require a longer time to go to completion (Table 1, en-