A versatile and operationally simple base-catalyzed multi-component domino reaction between a,b-unsaturated carbonyl compounds, aldehydes, and alcohols is described, providing a new efficient, and stereoselective one-pot preparation of trisubstituted alkenes and 1,3-dienes.Functionalized alkenes are useful intermediates and their preparation is of paramount importance in organic chemistry. 1 The wide spectrum of applications ranging from simple modifications up to the field of total synthesis of bioactive natural products has stimulated a huge interest, resulting in the development of an impressive number of synthetic methods. 2-4 Among them, representative examples such as simple ionic, thermal, or radical elimination reactions, dehydration of alcohols or direct olefination of carbonyl compounds based on Wittig/Horner-Emmons/ Peterson/Julia type condensations or other analogues largely lead the way. 5-12 However, many of these methodologies suffer from poor stereoselectivity, unsatisfactory yields, costly reagents, and/or time consuming procedures. In particular, the preparation of densely functionalized double bonds such as trisubstituted olefins and 1,3-dienes 13-16 is a particularly difficult task and simple direct methods are scarce. 4,17,18 Usually, multi-step procedures are required such as metal-catalyzed cross-coupling of vinylic halides [19][20][21][22] or selective transformations of BaylisHillman adducts. 23-30 This is why the synthesis of highly functionalized and stereodefined alkenes is a challenging problem which justifies the need for new simple complementary approaches. 31Our ongoing interest in multi-component domino transformations 32-35 has led us to an operationally simple and efficient one-pot stereoselective synthetic method for both trisubstituted olefins and 1,3-dienes starting from simple aldehydes. Our approach entails a base-induced domino sequence starting with the oxa-Michael addition 36,37 of alcohols 3 to a,b-unsaturated acceptors 1 followed by an intermolecular aldol/dehydration step with aldehydes 2. The overall oxa-Michael/aldol/dehydration sequence gives the expected condensation products 4 with a stereodefined trisubstituted double bond (Scheme 1).
Scheme 1Michael addition of heteronucleophiles is a well-known process, but utilization of alkoxides has received little attention over the years. One of the first examples of a related sequence with methyl acrylate, aromatic aldehydes, and methanol in the presence of a stoichiometric amount of base was proposed as a simple entry to 2,3-difunctionalized acrylic acids. 38 Recently, a short route to tetrahydroxanthenones was developed based on an intermolecular oxa-Michael addition of 2-hydroxybenzaldehydes to cycloalkenones followed by an intramolecular aldol reaction. 39 Alternatively, a similar transformation was observed using the Baylis-Hillman reaction with 2-hydroxybenzaldehydes which evolved through an intramolecular oxa-Michael/dehydration sequence leading to 2H-chromene derivatives. 40 Finally, recent work has shown the eff...