Phosphane-catalyzed [3+2] annulation of allenoates with aldehydes: a simple and efficient synthesis of 2-alkylidenetetrahydrofurans.

Five-membered oxygen-containing heterocycles are important structural components in a diverse range of naturally occurring and pharmacologically active molecules. Their widespread occurrence in the structures of natural or artificial bioactive substances has stimulated considerable interest in the development of new, efficient preparation methods. Among numerous known synthetic methods, the convergent annulation, which features both C O and C C bond formation in one step, is one of the promising strategies to construct oxygen-containing heterocycles from simple and stable starting materials. Previously, only a few such examples were reported. Herein, we report a phosphane-catalyzed [3 +2] annulation of g-methyl allenoates with aromatic aldehydes. This annulation provides a convergent and efficient synthesis of 2-alkylidenetetrahydrofurans, which are versatile synthetic building blocks for a vast array of 5-membered oxygenated heterocycle derivatives. Recently, phosphane-catalyzed cycloaddition reactions of allenes have been widely applied in the construction of a variety of carboand heterocycles. Among them, [3+2] and [4+ 2] cycloadditions of allenoates with electron-deficient olefins or imines are especially attractive because they provide metal-free and highly atom economic strategies to build fiveand six-membered ring systems. However, aldehydes as electrophiles in reactions with allenoates show distinctive reactivity patterns relative to electron-deficient olefins and imines. As a result, the corresponding [3+2] and [4+ 2] annulations of allenoates with aldehydes have not been developed to the same extent as annulations with activated olefins or imines. On the basis of experimental and theoretical studies by Kwon and co-workers, the difference in the reactivity patterns of allenoates with aldehydes, olefins, and imines has been well rationalized. 9] Under the nucleophilic catalysis of a phosphane, activated olefins and imines undergo predominant a addition to the nonsubstituted allenoate (R’= H), leading to [3+ 2] cycloaddition products (Scheme 1, pathway A). In sharp contrast, aldehydes undergo exclusive g addition to the allenoate, resulting in the formation of a cyclic adduct, for example, 1,3-dioxan-4-ylidene, rather than the normal [3+2] cycloaddition product (Scheme 1, pathway B). It is also understood that a substituent, (e.g., methyl) at the a carbon of allenoates can alter the inherent reactivity pattern of nonsubstituted allenoates. For example, under the catalysis of nucleophilic phosphanes, both activated olefins and imines can exclusively undergo g addition to a-methyl allenoates, resulting in [4+2] annulation reactions (Scheme 1, pathway C); for aldehydes no such reaction, with a-substituted allenoates, has been reported in the literature. Intrigued by these elegant studies, especially from the Kwon group, we suspected that the introduction of a substituent at the g carbon of an allenoate may be able to alter the normal regioselectivity of g addition of aldehydes to allenoates. Although it is known that g-substituted allenoates still retain similar reactivity patterns with activated olefins and imines to those of nonsubstituted allenoates. To evaluate this hypothesis, we began our investigation with allenoates bearing a small substituent like methyl (2 a) or a bulky substituent like phenyl (2 b) or tertiary butyl (2 c) at the g carbon. The preliminary experimental results showed that in the presence of PPh3 (20 mol%) the reaction of gmethyl allenoate (2 a) and o-chlorobenzaldehyde (1 a) proceeded smoothly to give the new products (3 a, 4 a, and 5 a) in appreciable yields (Scheme 2). Under similar conditions, however, neither g-phenyl nor g-tert-butyl allenoates afforded any new products. Clearly 3 a, 4 a, and 5 a were formed by unprecedented reaction pathways. The tetrahydrofuran derivative 3 a is indeed the product of a [3+2] annulation, resulting from the incorporation of three carbons of the allenoate with the carbonyl of the aldehyde; the g-methyl of 2 a is directly involved in the carbon–carbon bond-forming [a] S. Xu, L. Zhou, R. Ma, Prof. Dr. H. Song, Prof. Dr. Z. He The State Key Laboratory of Elemento-Organic Chemistry and Department of Chemistry, Nankai University 94 Weijin Road, Tianjin 300071 (China) Fax: (+86) 22-23501520 E-mail : zhengjiehe@nankai.edu.cn Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200901276.