Intramolecular Aldol-Type Reaction and Allylation

Intramolecular carbon-carbon bond formation is an effective means of creating a variety of functionalized carbocyclic and heterocyclic ring systems. Apparently, proper choice of Lewis acid promoters and conditions enables stereoselective ring construction by use of la and other Lewis acids. 

Bis(trimethylsilyl) enol ethers react with a variety of 1,4-dicarbonyl substrates in the presence of a Lewis acid promoter to afford [3 -t- 4] annulation products [45]. The use of TiCU, employed in the initial studies, poses difficulties and complete regiocon-trol in the cyclization is often lacking. Among many Lewis acids tested, surprisingly, la promotes the [3 -(- 4] annulation with high regio- and diastereoselectivity (Sch. 14). 

Other intramolecular aldol reactions have been reported. In the first total synthesis of A -capnellene-8/ ,10a-diol and A -capnellene-3y3,8/3,10a-triol Shibasaki et al. reported that excess la with Et3N effects the cyclization of intermediate 16 giving 17 in 42 % yield (Sch. 15), although a wide variety of different acidic and basic reagents meet with failure [46]. 

Fluoride- or Lewis acid-induced cyclization of alkylidene 1,3-dioxo compounds with an allylic silane moiety has also been studied. When la was used very high trans preference was observed. 

A stereoselective tandem Sakurai-carbonyl-ene reaction for the synthesis of steroid derivatives has been reported [48]. When LtAlCl2 and la were employed in this cyclization, stereochemical control was different. The cyclization product obtained with la is only 19 (Sch. 17), even though the starting material contained all four geometrical isomers use of LtAlCl2 resulted in a mixture of two different stereoisomers in lower yield. 

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