Building vicinal diols

Enantiopure epoxides and vicinal diols are important versatile chiral building blocks for pharmaceuticals (Hanson, 1991). Their preparation has much in common and they may also be converted into one another. These chirons may be obtained both by asymmetric synthesis and resolution of racemic mixtures. When planning a synthetic strategy both enzymic and non-enzymic methods have to be taken into account. In recent years there has been considerable advance in non-enzymic methods as mentioned in part 2.1.1. Formation of epoxides and vicinal diols from aromatics is important for the break down of benzene compounds in nature (See part 2.6.5). 

The Selective Blocking of Trans-Diequatorial, Vicinal Diols — Applications in the Synthesis of Chiral Building Blocks and Complex Sugars. Ziegler. T, Angew. Chem. Int. Ed. Engl 1994,2272. 

These very interesting chiral building blocks are employed in aldol reactions, and in the synthesis of enantiomerically pure vicinal diols (eq IS) and 3-oxo esters and acids bearing... 

Finally, Kibayashi used aqueous versions of the intramolecular acyl-nitroso Diels-Alder reaction to good effect in his stereocontrolled syntheses of (-)-swainsonine (6.28) [78] and (-)-pumiliotoxin C (6.34) [79] (Schemes 1.13 and 1.14). In each case, oxazinolactam cycloadducts (cf. 6.32 and 6.38) served as key functional chiral building blocks for the remaining synthetic operations. For example, retrosynthetic analysis of the trihydroxy-indohzidine system of swainsonine (6.28) reveals that the pyrrolidine ring of this target can be formed by amine alkylation (cf. 6.29) while the vicinal diol can be installed via substrate-controlled cw-hydroxylation of a (Z)-allyl... 

In this section, we will focus on linear cascades combining m-TAs with hydrolases or lyases. For example, the synthesis of (2S,3S)-2-aminopentane-l,3-diol from propanal and p-hydroxypyruvate was facilitated [50] by coupHng a mutated transketolase from E. coli (TK D469T) [51] and an m-TA from C. violaceum [31] (Scheme 4.14). Such vicinal chiral amino alcohols represent an important class of building blocks and pharmaceutical intermediates. 

Optically active, vicinal chlorohydrins can serve as building blocks in much the same capacity as epoxides, azido alcohols, or diols. Enantioselec-tive access to chlorohydrins such as 165 was made possible through Henry s discoveiy of a Pd-catalyzed interrupted Wacker oxidation of olefins (Equation 28) [136, 137]. The process employs tetrasulfonated BINAP 166 as a chiral ligand embedded within the bimetallic triketone complex 164 [136]. 

---