Some recent advances in the use of titanium reagents for organic synthesis
A large variety of allylic triphenoxy-titanium reagents, generated by trans-metallation from the corresponding lithium or magnesium derivatives, add to aldehydes and unsymmetrical ketones at the more highly substituted allylic carbon atom to give two diastereomers, generally in a ratio of 3:1 to more than 50:1. Thus, tertiary homoallylic alcohols, and from them —hydroxy-carboxylic acids of a given configuration are readily accessible (Table 1). The products from titanium tetrachloride and methylor phenyl-isocyanide, which have the structure of trichlorotitanio-imidchlorides (9), add to aldehydes and ketones to give after hydrolysis a-hydroxy-carboxamides in high yields (Scheme 3). A building block approach is described for the alkylative amination of aldehydes to chain-elongated amines (12). With non-enolizable aldehydes, a Li-amide is first added to the carbonyl group, followed by Li/TiCl3 exchange with titanium tetrachloride and addition of two equivalents of an organolithium compound (Scheme 4). With enolizable aldehydes, dialkylamino-trichloro-titanium is first added to the carbonyl group, followed by replacement of C13TiO by an R-group with alkyllithium (Scheme 5). With the chiral organotitanium compounds bearing binaphtholate (25, 26) or tartaric acid-derived diolates (27, 28), phenyl groups can be transferred to aromatic aldehydes, and methyl groups to aromatic or aliphatic aldehydes with high enantioselectivity (Scheme 6 and Table 2). A) Introduction Since we have published two extensive review articles dealing very generally with this subject,1'2 we will describe here only a few new results which were obtained most recently. Also, only investigations done in our own laboratory will be mentioned in the present pa— per.35 The material may be divided into four groups: allylic triphenoxy-titanium reagents, trichlorotitanio imidchlorides (from isocyanides and tetrachlorotitanium) as reagents for Passerini-type reactions, alkylative aminations (Mannich-type reactions) with titanium derivatives, and asymmetric additions of chiral organotitanium derivatives to aliphatic and aromatic aldehydes B) Selective Allylations with Titanium Reagents One of our first observations concerning organotitanium reagents was their selectivity in differentiating between functional groups. This is evident from Fig. 1, in which capillary gas chromatograms (CGC) are shown of the mixtures obtained upon addition of methyllithium, methylmagnesium bromide, and methyl-triisopropoxy-titanium to a 1:1-mixture of benzaldehyde and acetophenone. The addition of a crotyl-metal derivative to the same mixture of carbonyl 1807 1808 D. SEEBACH et al.