Two-Carbon Chain Elongation of Aldehydes

5 Two-Carbon Chain Elongation of Aldehydes 13.5.5.1 Asymmetric Aldol Reactions 

SCHEME 13.31 Asymmetric synthesis of L-arabinitol derivatives via stereoselective dihydroxylation of an enantiomerically pure ally lie alcohol. 

SCHEME 13.32 Asymmetry induced by a chiral auxiliary in the aldol condensation of glycoaldehyde. 

SCHEME 13. 33 Mukaiyama s asymmetric aldol reactions total synthesis of D-ribose, 4-C-methyl-D-ribose and 6-deoxy-L-talose. 

Finally, recent work published by the MacMillan Group [74] demonstrates the feasibility of utilizing selective aldol reactions to prepare carbohydrates in as little as two steps. 

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Several s)uitheses of aminodeoxypentoses have employed a similar approach in which a three-carbon starting material is condensed with a two-carbon entity [237]. A synthetic equivalent of the glycoaldehyde anion, the dioxaborole 98 (O Scheme 46) has been used for the carbon chain elongation of aldehydes. Thus L-ribose is prepared from the addition of... 

The Homer-Wadsworth-Emmons reaction is among the most important reactions for effecting a two-carbon chain elongation of a carbonyl functional group - " It can be described as a general synthetic protocol for the conversion of aldehydes and ketones into aji-unsaturated carbonyl compounds and their derivatives " ... 

In another report, paromamine 92 was converted to the pseudodisaccharide 100, which is a constituent of the structure of oxyapramycin 101 (compounds 100, 101). Two-carbon chain elongation was performed by Wittig reaction on a 5 -aldehyde derivative followed by osmium tetraoxide hydroxylation, which after lactonization in the basic condition, followed by reduction and deprotection, afforded compound 100 [61]. 

Chain elongation of ArCHO. Transformation of ArCHO to 2-arylidene derivatives of Meldrum s acid followed hy reduction with PhSiH3 accomplishes homologation of the aldehydes hy two carbon units. The second step is catalyzed by Mo(CO)6. ... 

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]. 

The next phase focused on the goal of elaboration of the side chain in the desired sense. The primary alcohol function at C7 was unveiled by hydrogenolysis (Pd(OH)2/EtOAc-MeOH). Oxidation of the resultant compound 13 with chromic oxide pyridine afforded aldehyde 14, which was now to be elongated through some variation of a Homer-Emmons type of reaction. Shortly before tiiese investigations were launched. Still had demonstrated the use of phosphonate 15 as a device to achieve the two-carbon extension of an aldehyde to a Z-enoate (12). Happily, application of the Still method to compound 14 afforded the desired 16, mp 120-121° C, in 80% yield as a 20 1 mixture of Z E enoates. 

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