Metal enolates in organic synthesis
Metal enolates play an important role in organic synthesis and in particular metal enolate mediated aldol type reactions provide very useful synthetic tools in stereoselective and asymmetric carbon-carbon bond formations. Three types of metal enolate mediated aldol reactions developed in our laboratory are discussed. During the past decade, generations and reactions of various metal enolates have been extensively studied and successful applications to the controlled formation of carbon-carbon bonds have been realized under mild conditions. Besides the well-studied aldol reaction based on lithium enolates, very versatile regioand stereoselective carbon-carbon bond forming reactions have been established by the use of silyl enol ethers-Lewis acids, vinyloxyboranes, and stannous e'iolates (Ref. 1). In this article, the chemistry of these three types of aldol reactions is discussed. They are: 1. The titanium tetrachloride promoted aldol reaction of silyl enol ethers. 2. Vinyloxyborane mediated aldol reaction. 3. The stannous enolate mediated aldol reaction. I. THE TITANIUM TETRACHLORIDE PROMOTED ALDOL REACTION (Ref. 2) Aldol reaction has long been recognized as one of the most useful synthetic tools and the reaction is usually carried out under basic conditions. However, under classical aldol reaction conditions in which basic media are employed, dimers, polymers, self-condensation products, or c,i3-unsaturated carbonyl compounds are invariably formed as by-products. Useful synthetic methods have been developed recently to alleviate those difficulties, especially under basic conditions, the lithio derivative mediated method offers one of the solutions to those problems (Refs. 1,3). On the other hand, there appeared no practical procedure for cross aldol reaction carried out under acidic conditions. Enol ethers react with acetals or ketals by the promotion of Lewis acids to give aldol-type adducts. However, acid catalyzed reactions are often accompanied with undesirable side reactions, when stoichiometric amounts of carbonyl compounds and enol ethers are employed (Ref. 4). The use of stoichiometric amounts of titanium tetrachloride, trimethylsilyl enol ether, and a carbonyl compound is a great advance in directed aldol reaction. Powerful activation of carbonyl groups by TiCl enables the nucleophilic attack by trimethylsilyl enol ethers to form trimethylsilyl chloride and the titanium salt of the aldol-type product. In this case, undesirable dissociation of the adduct is inhibited by the formation of a stable titanium chelate, hydrolysis of which yields the desired -hydroxy ketone (Ref. 5). This type of reaction is also promoted by various other Lewis acids such as SnCl, BF3'OEt2, AlCl3, and so on. Among these acids, titanium tetrachloride was found to be superior to the other Lewis acids with respect to yields. The reaction proceeds with retention of the regiochemical integrity of the starting silyl enol ethers to afford the corresponding aldol regiospecifically. Starting enol ether compounds, silyl enol ethers, can be conveniently prepared regioselectively under either kinetically or thermodynamically controlled conditions. 1749