Deuteration enantioselective

Enantioselective reduction is not possible for aldehydes, since the products are primary alcohols in which the reduced carbon is not chiral, but deuterated aldehydes RCDO give a chiral product, and these have been reduced enantioselectively with B-(3-pinanyl)-9-borabicyclo[3.3.1]nonane (Alpine-Borane) with almost complete optical purity. ... 

Table 6.7. Enantioselective hydrogenation and deuteration of alkenes catalyzed by (R)-(ebthi)Zr-binol and MAO (at 25 °C).

The data in Table 6.7 illustrate that when the non-racemic (ebthi)Zr system is used to catalyze the hydrogenation of prochiral alkenes, moderate levels of enantiofacial differentiation are observed (23—65% ee). Enantioselective deuteration of pentene occurs in low yield but shows noticeable enantioselection (23% ee). The same reaction with styrene proceeds in 61% yield and with moderate enantioselectivity (65% ee). Hydrogenation of 2-phenyl-l-pentene proceeds in excellent yield but with poor control of stereochemistry (95% yield, 36% ee). 

The enantioselectivity is determined in an irreversible step after the chiral atom has been formed. Deuteration experiments have shown that styrene... 

Garbe L-A, Tressl R (2004) Metabolism of deuterated t/jreo-dihydroxy fatty acids in Saccha-romyces cerevisiae Enantioselective formation and characterization of hydroxylactones and y-lactones. Helv Chim Acta 87 180... 

Cpsymmetric organolanthanide complexes exhibit moderate to good enantioselectivities in the hydrogenation and deuteration of styrene and 2-phenyl-1-butene.433 Cationic iridium-phosphanodihydrooxazole complexes are more efficient catalysts for the asymmetric hydrogenation of unfunctionalized aryl-substituted alkenes. The best catalyst (42) gives high yield (>99%) and excellent enantioselectivity (97% ee) in the hydrogenation of ( )-l,2-diphenyl-l-propene 434... 

Asymmetric transfer hydrogenation of benzaldehyde-l-d with (R,R)-28 and (CH3)3COK in 2-propanol gave (R)-benzyl-l-d alcohol quantitatively in 98% ee (Scheme 41) [114], Introduction of electron-donating and electron-accepting groups at the 4 position had little effect on the enantioselectivity. Catalytic deuteration of benzaldehydes was achieved by use of the same complex (R,R)-28 and a 1 1 mixture of formic acid-2-d and triethylamine to give the S deuter-io alcohols in up to 99% ee (Scheme 42) [114], The dt content in the product alcohol was >99%. Only a stoichiometric amount of deuterium source is required to complete the reaction. 

I.4.2.6. 1-Deuterio Aldehydes Asymmetric hydrogenation of 1-deuterio benzaldehydes with Ru(OCOCH3)2[(5)-binap] in the presence of 5 equiv. of HC1 gives the corresponding chiral 1-deuterio alcohols with up to 89% ee (Scheme 1.75) [280]. The heteroatom substitution at the C2 position in the benzene ring tends to increase the enantioselectivity due to the heteroa-tom/metal interaction. This catalyst is less reactive in deuteration of benzaldehyde. 

Scheme 22 Enantioselective addition of diisopropylzinc to aldehyde 11 using chiral a-deuterated alcohols as chiral inducers...

The lithiation and silylation of the amide 71 is enantioselective for a very different reason. When the intermediate organolithium is made from the racemic stannane 72, it still gives the product 74 in good enantioselectivity provided the electrophile reacts in the presence of (-)-sparteine.72 The reaction must therefore be an enantioselective substitution. Furthermore, reaction of the deuterated analogue 75 gives a result which is not consistent with asymmetric deprotonation yield, deuterium incorporation and product ee are all high. 

The mechanism by which organolithium 73 reacts enantioselectively is illustrated in scheme 6.2.1. For a reaction in which (-)-sparteine determines the enantioselectivity in the substitution step, and not the deprotonation step, deuterium incorporation will simply reflect the magnitude of the kinetic isotope effect. The product s ee will be the same irrespective of whether or not the starting material is deuterated (contrast the reactions of d-395 in section 5.4, summarised in scheme 5.4.1). 

Section 5.4 describes the enantioselective deprotonation of a deuterated benzylamine derivative 431 to give a configurationally unstable organolithium 432.75 Over a period of minutes, in the presence of (-)-sparteine, the organolithium 432 gave products of increasing ee as the organolithiums equilibrated under thermodynamic control to the more stable 432-(-)-sparteine complex, a process that could be accelerated by the precipitation of the complex. 

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