Alternative Approaches to Titanium Enolate Generation

Although the direct generation of titanium enolates is typically the most useful method of generating titanium enolates for aldol reactions, other methods have been described. Grubbs and Stille reported that titanium enolates could be generated by reaction of biscyclopentadienyltitanium al-kylidene complexes and acyl halides [93]. Oshima and coworkers reported the formation of titanium enolates from a-iodoketones with allylsilane and titanium tetrachloride [94]. Mukaiyama and coworkers reported the generation of titanium enolates from a-bromoketones on treatment with TiCh and copper powder [95]. 

Titanium enolate aldol reactions have been shown to be very effective for control of relative and absolute stereochemistry in acetate aldol and both syn and anti aldol reactions. The use of readily available and inexpensive titanium reagents make these methods convenient for large-scale synthesis. The synthetic potential of a variety of aldol reactions has been demonstrated by highlighting the synthesis of numerous bioactive complex natural products. The significance of enantio- and diastereoselection in synthesis, particularly in this pharmaceutical age, ensures that titanium enolate aldol reactions will remain an important part of organic synthesis for years to come. There is no doubt that unprecedented success has been achieved in the development of a variety of titanium enolate aldol reactions in the past decade. Much new potential and other exciting possibilities remain to be 

2 The term chiral auxiliary was first introduced by Fliel. Fliel, F. L. Tetrahedron 1974, 30, 1503 and references cited therein. 

Gonzalez, A. Aiguade, J. Uepi, F. Vilaeeasa, J. Tetrahedron Lett. 1996, 37, 8949. 

Feinguelli, F. Pieematte, O. Pizzo, F. Sgappini, A. M. Gazz. Chim. Ital. 1995, 325, 195. 

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