The remarkable progress that has been achieved in stereoselective carbon-carbon bond formation is mostly due to the development of novel organometallic reagents. An already classical example is provided by organotitanium compounds, the synthetic potential of which was recognized in the early 1980s.[ 11 In comparison with Grignard and organolithium compounds from which they are generated by a simple in-situ transmetalation, the titanium reagents exhibit an often dramatically improved chemo-and diastereoselectivity, as shown by the addition to aldehydes and ketones.[2] Whereas methyl lithium (la) cannot differentiate between benzaldehyde and acetophenone the methyl titanium reagent (I b) is perfectly aldehyde selective (Scheme 1). Equally impressive is the diustereoselectivity thatin favor of the Cram product (3u) -is observed in the addition of (1 b) to chiral aldehydes such as (2). In contrast, powerful enuntioselective methods have been restricted to a few examples for a long time (e.g. (4) -+ (5) [3]). Obviously, the incorporation of chelating ligands into compounds of type (6u) is not necessarily associated with a sufficient stability of configuration.This goal, however, is achieved if a pentuhupto cyclopentadienyl ligand is incorporated into the reagent. Coordination of chiral coligands (two unidentate coligands X or one bidentate coligand with C2-symmetry to avoid the generation of an undesired metal stereo-center) leads to compounds of type (6b). Carbohydrates turned out to be especially effective in reagents that allow high asymmetric induction both in the nucleophilic addition to aldehydes and in aldol reactions.[4] A potent allyl transfer reagent is complex (10) which can be prepared in a 1OOg scale from the chloro precursor (9) following a twostep sequence from cyclopentadienyltitanium trichloride (7) and diacetone glucose (DAGOH) (8).[5] Complex 10 prefers addition to the re--face of aldehydes, thereby affording homoallyl alcohols (11) in good chemical yields (50-90%) and very good enantioselectivity (86-95 % ee). The selectivity depends only to a minor extent on the temperature, as shown in the addition of (10) to benzaldehyde: The ee value drops from 90 % to 80% when the temperature is raised from -74°C to 0°C. Controlled hydrolysis of the reaction mixture affords undefined titanate species that are transformed to the trichloride (7). Thus, both the metal component and the released chiral auxiliary can be recovered (Scheme 2).The enantioselectivity of the allyl transfer depends markedly on the combination of the coligands: It is essential that two carbohydrate ligands are attached to the metal center together with one allyl group. The ee value of the allylation of benzaldehyde decreases to 46 % and 21 %, respectively, if the bis(diacetone glucose) complex CpTiC1(ODAG)2 (20)
Organic Synthesis Highlights I1Edited by Herbert Waldmann OVCH Verlagsgesellschafi mbH,1995