Reduction polypropionates

A reiterative application of a two-carbon elongation reaction of a chiral carbonyl compound (Homer-Emmonds reaction), reduction (DIBAL) of the obtained trans unsaturated ester, asymmetric epoxidation (SAE or MCPBA) of the resulting allylic alcohol, and then C-2 regioselective addition of a cuprate (Me2CuLi) to the corresponding chiral epoxy alcohol has been utilized for the construction of the polypropionate-derived chain ]R-CH(Me)CH(OH)CH(Me)-R ], present as a partial structure in important natural products such as polyether, ansamycin, or macro-lide antibiotics [52]. A seminal application of this procedure is offered by Kishi s synthesis of the C19-C26 polyketide-type aliphatic segment of rifamycin S, starting from aldehyde 105 (Scheme 8.29) [53]. 

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]. 

Vogel also used (-)-5, prepared from 2,4-dimethylfuran, to show that a sequence involving stereoselective functionalization, fragmentation via Baeyer-Villiger oxidation and exhaustive reduction constitutes a quick assembly of optically pure polypropionate arrays with four contiguous stereocenters, Eq. 82 [14,132]. 

The Evans aldol reaction using chiral p-keto imide 23 as a dipropionate building block is also very effective for the construction of polypropionate segments in polyoxomacrolides (Scheme 2) [8]. The diastereoselective aldol reaction of 23 via different metal enolates (Ti, Sn, and B enolates) afforded three kind of aldols, syn-syn-24, anti-syn-25, and anti-anti-26, with high diastereoselectivity, respectively. The subsequent stereoselective reduction of the resulting p-hydroxy ketones 24-26 provides various types of dipropionate units. Based on this strategy, the... 

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. 

Polypropionates possessing chiral chains compose a big group of natural products called polyketides. Polyketides are produced in nature by Claisen condensation and the subsequent reduction. However, people think that aldol reactions should be adequate to construct polypropionate skeletons because an aldol reaction constructs two stereo-genic centers at the a and 3 positions. For example, as shown in Scheme 8.1, erythromycin A would be synthesized by repetition of aldol reactions and manipulation of (3-hydroxy groups. Therefore, the stereoselective aldol reaction should be a key to the synthesis of polypropionates, and chemists have developed many types of aldol reactions. ... 

The synthesis of polypropionate by the (3-ketoimide-aldol reaction features the subsequent stereoselective reduction of the (3-ketone. As shown in the total synthesis of 6-deoxyerythronolide B 59 (Scheme 8.8), aldol adduct... 

Brazeau JF, Mochirian P, Prevost M, Guindon Y. Stereopentads derived from a sequence of Mukaiyama aldolization and free radical reduction on a-methyl-(3-alkoxy aldehydes a general strategy for efficient polypropionate synthesis. J. Org. Chem. 2009 74 64-74. 

Hydroxy-8-lactone such as 209 constitutes the structural motif of natural polypropionates and an intermediate in the step-by-step biosynthesis of these compounds. As shown in Scheme 22.34, 209 is readily obtained by diaster-eoselective reduction of ketone 202, followed by ozonolysis of its enol ester moiety. ... 

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