Polypropionate 1,3-diols

During the course of the development of our group s alkylation/reductive decyanation strategy, a very reliable method for distinguishing between syn-and anfz-l,3-diols was discovered [17,18]. The acetonide methyl groups reliably display diagnostic C-NMR chemical shifts, allowing for stereochemistry to be determined simply by inspection (Fig. 1). Evans later extended the C-NMR chemical correlation to polypropionate chains [19,20]. 

In another report, Panek and Jain used chiral allylsilane methodology for construction of C1-C17 polypropionate fragment of ru-tamycin B and oligomycin C. The aldehyde partner used for the sequence consisted of a diol protected as a di-f-butylsilylene 18. The reaction proceeded in the presence of TiCU in excellent diastereoselectivity and yield (eq 9). 

Synthesis of polypropionate marine natural product (+)-membrenone C and its 7-epi-isomer has been reported using a key desymmetrization technique to create five contiguous chiral centers frombicyclic precursor 36. The diol was protected using di-f-butylsilyl bis(trifluoromethanesulfonate) and further elaborated into the natural product and its epimer (eq 14). In a separate communication, Perkins et al. utilized di-f-butylsilyl bis(trifluoromethanesulfonate) for synthesis of a model system en route to the pol)q)ropionate natural products auripyrones A and... 

Much tvork in the field of aldol reactions of ketones tvas performed by Evans to enable the synthesis of polypropionate natural products. They demonstrated that j5-ketoimides like 159 vere selectively and completely enolized at the C4 position rather than the potentially labile methyl-bearing C2 position, most probably because steric factors prohibited alignment of the carbonyl groups necessary to activate the C2 proton. As sho vn in Table 2.29, it vas demonstrated that these compounds vould react vith aldehydes to provide syn-syn product 161, via titanium enolates, vith good yield and excellent selectivity, and the corresponding syn-anti product 162 could be favored by use of a tin enolate reaction [58]. They invoked the chelated transition state assembly 160 to explain the product stereochemistry observed, in vhich the C2-methyl group directs diastereofacial selectivity. Interestingly, reduction vith Zn(BH4)2 provided the syn diol diastereoselec-tively. 

Gao X, Han H, Krische MJ. Direct generation of acyclic polypropionate stereopolyads via double diastereo- and enantioselective iridium-catalyzed crotylation of 1,3-diols beyond stepwise carbonyl addition in polyketide construction. J. Am. Chem. Soc. 2011 133 12795-12800. 

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