Titanium tetraisopropoxide reaction with aldehydes

Yamamoto et al. have reported a chiral helical titanium catalyst, 10, prepared from a binaphthol-derived chiral tetraol and titanium tetraisopropoxide with azeotropic removal of 2-propanol [16] (Scheme 1.22, 1.23, Table 1.9). This is one of the few catalysts which promote the Diels-Alder reaction of a-unsubstituted aldehydes such as acrolein with high enantioselectivity. Acrolein reacts not only with cyclo-pentadiene but also 1,3-cyclohexadiene and l-methoxy-l,3-cyclohexadiene to afford cycloadducts in 96, 81, and 98% ee, respectively. Another noteworthy feature of the titanium catalyst 10 is that the enantioselectivity is not greatly influenced by reaction temperature (96% ee at... 

Yamamoto and colleagues prepared chiral titanium catalyst 420 from titanium tetraisopropoxide and chiral binaphthol 419 (equation 126). This catalyst gave high asymmetric inductions in various Diels-Alder reactions of a,/J-unsaturated aldehydes with cyclopen-tadiene and 1,3-cyclohexadiene260. 

Quenching the anion 225 with titanium tetraisopropoxide 2 affords the ate complex 226, which reacts 100% regio- and distereoselectively with aldehydes to afford the threo adducts 227 (>95% conversion, 80% isolated by distillation)90) (Equation 71). This methodology is simpler than analogous reactions of boron reagents122). Furthermore, even ketones react threo-selectively (Equation 72)90). Since the adducts can be converted by adds (anti elimination) or KH (syn elimination) into the two possible diastereomeric dienes122), the sequence is synthetically useful. 

Additions to Aldehydes. Alkylation of aromatic and aliphatic aldehydes with a combination of titanium tetraisopropoxide, Ti(0-/-Pr)4, and diethy Izinc, ZnEt2, in the presence of a catalytic amount of the bis-sulfonamide la leads to formation of (S)-l-phenyl-1-propanol 4 with high enantioselectivity (eq 2, Table 1). Use of the (R,7 )-l,2-(trifluoromethanesulfonamido)-cyclohexane lb [CAS 122833-60-7] allows for an equally selective reaction, but at exceptionally low catalyst loadings. In the case of aromatic aldehydes, these reactions are fairly rapid, requiring at most 2 hours to reach full conversion. 

Allyltitanium complexes (22) readily add to carbonyl compounds with high regio- and stereo-selection. They are prepared by reaction of a chlorotitanium complex (21) with an allyl-magnesium or -lithium derivative (equation 13). Some of these unsaturated Ti complexes, like (23)-(25) in Scheme 2, obtained from allylmagnesium halides or allyllithium by reaction with titanium tetraisopropoxide or titanium tetramides, are known as titanium ate complexes . The structure of these ate complexes, at least from a formal point of view, can be written with a pentacoordinate Ti atom. Some ate complexes have synthetic interest, as is the case of (allyl)Ti(OPr )4MgBr which shows sharply enhanced selectivity towards aldehydes in comparison with the simple (allyl)Ti(OPr )3. ... 

Keck almost simultaneously reported two procedures using chiral titanium catalysts 6A and 6B for the enantioselective addition of allyltributyltin to aldehydes [11]. In the first procedure, the catalyst 6A is prepared from a 1 1 mixture of (R)-binaphthol and titanium tetraisopropoxide. The second procedure for the preparation of 6B, in contrast, requires a 2 1 mixture of BINOL, Ti(0 Pr)4, and a catalytic amount of CF3SO3H or CF3CO2H. Using 10 mol % of the catalyst 6A or 6B, a variety of aromatic, aliphatic, and a,P-unsaturated aldehydes are efficiently transformed into the corresponding optically active homoallylic alcohols with high enantioselectivity. An improved procedure was later published for the catalytic asymmetric allylation reactions using the 2 1 BINOL/Ti catalytic system [12]. 

Khan and coworkers prepared the ligand 23, which led to complex 24 bearing four titanium atoms after the addition of titanium tetraisopropoxide and water (Scheme 7.17). The cyanation of aldehydes with KCN/AC2O works similarly to complex 19, giving acylated cyanohydrins in nearly quantitative yields and 85-95% enantiomeric excesses. Importantly, complex 24 precipitated after addition of hexane to the reaction mixture, and the filtrated catalyst was reused without affecting the enantiomeric excess (the yield decreases to 88% after 4 runs). 

Optically active propargylic alcohols can be prepared from terminal al-lynes and carbonyl compounds, via an in situ metalation with diethylzinc (or dimethylzinc), and excellent yields and enantioselectivities were obtained by using substoichiometric amounts of titanium tetraisopropoxide and readily available BINOL (Scheme 7.31). Aliphatic and a,(3-unsaturated aldehydes were also converted with success by performing the reaction in ether. ... 

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