Backvall’s catalyst

In 2007, Park s group showed that one of the two carbonyl ligands of Backvall s catalyst could easily be replaced with triphenylphosphane with the aid of trimethylamine A-oxide to give a novel analogue of Backvall s catalyst, depicted in Scheme 4.12. Interestingly, this catalyst promoted the racemisa-tion of alcohols at room temperature in the presence of a catalytic amount of silver oxide. The catalytic species were stable in air and reusable at least ten times for the DKR of alcohols, although stoichiometric amounts of Ag20 were required. The DKR of phenylethanol under these conditions is described in Scheme 4.12. 

Scheme 4.11 DKR of fluorinated aryl alcohols with Backvall s catalyst.

Scheme 4.12 DKR of phenylethanol with Backvall s catalyst analogue.

Bn Backvall s catalyst Scheme 4.23 DKRs of diols with Backvall s catalyst. 

Another analogue of Backvall s catalyst was reported by Kanerva s group for the DKR of secondary alcohols such as 1-phenyl- and l-(furan-2-yl)ethanols. 

Scheme 4.33 DKR of 1,2-diarylethanols with an analogue of Backvall s catalyst.

The reaction was performed with CAL-B in the presence of isoproprenyl acetate as the acyl donor in toluene. This new catalyst showed a higher stability combined with an improved performance as an alcohol racemisation catalyst in comparison with its well-known analogue, Backvall s catalyst. The enhanced stability of this catalyst compared with Backvall s catalyst could be related to the better shielding of the metal centre towards hydrolysis, thus hindering catalyst decomposition. As shown in Scheme 4.34, the corresponding acetates were obtained in high to excellent yields and excellent enantioselectivity of >97% ee. 

PhCO Backvall s catalyst Novozym 435 t-BuOK, NajCOa... 

The asymmetric synthesis of chiral fluoroorganic compounds plays an important role in the development of medicines, agrochemicals, and materials due to the influence of fluorine s unique properties. In this context, Bogar and Backvall investigated the DKR of various fluorinated aryl alcohols, in 2007. As shown in Scheme 8.17, a series of chiral fluorinated acetates were produced in remarkably high yields and enantioselectivities by using a combination of CALB with Backvall s catalyst in the presence of isopropenyl acetate as the acyl donor at room temperature. 

The lipase-ruthenium-catalysed DKR of other functionalised alcohols, such as diols, has been widely studied by Backvall et al. in recent years. These authors have developed a highly efficient synthesis of enantiopure diacetates of the symmetric diols, 2,4-pentanediol and 2,5-hexanediol, by combining Backvall s catalyst with lipase CALB, in the presence of vinyl acetate or isoproprenyl acetate as the acyl donor, respectively. Excellent yields, and diastereo- and enantioselectivities were obtained in both cases. 

In order to obtain (5 )-selective DKR of secondary alcohols, an enzyme with a complementary (5 )-stereoselectivity was needed, since the lipase-catalysed DKR provides only (R)-products. In this context, Park et al. reported, in 2003, the use of subtilisin instead of lipase, but the commercial form of subtilisin was not applicable to DKR, due to its low enzymatic activity and instability in non-aqueous medium. However, these authors succeeded in enhancing its activity and stability by treating it with a surfactant before use. In these conditions, the combination of subtilisin with an analogue of Backvall s catalyst and trifluoroethyl butanoate as the acylating agent... 

Scheme 8.36 Enzymatic DKR of aromatic chlorohydrins with Backvall s catalyst...

In 2009, Backvall s catalyst was also employed at a low catalyst loading (0.5 mol%) by these authors in combination with CALB to perform the DKR of l-(6-chloropyridin-3-yl)ethanol by using similar conditions. The corresponding acetate was achieved in 91% yield and enantioselectivity of >99% ee, as shown in Scheme 8.37. This reaction constituted the key step of a synthesis of a neonicotinoide pesticide derivative depicted in Scheme 8.37. These conditions were also applied by Gotor et al. to the total synthesis of (5)-rivastigmine, employed as a drug for the treatment of dementia of the Alzheimer s type. " As shown in Scheme 8.37, the key step of this synthesis... 

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