Homologation of carbonyls

A Wittig reaction of the 17-oxo-7(8-lla)-aheo-compound (106) led to the Ai7 20) compound (107). Homologation of carbonyl compounds to carboxylic... 

A one-carbon homologation of carbonyl compounds is an important and extensively used method for the preparation of desired carbonyl compounds . One-carbon ring-expansion or one-carbon homologation of ketones or aldehydes via a S-oxido car-benoid is a representative example of the homologation, but few methods have been reported . 

Diethyl [(2-tetrahydropyranyloxy)methyl]phosphonate is useful in the Wlttig-Horner synthesis of enol ethers, which are intermediates in one-carbon homologations of carbonyl compounds. This procedure is an adaptation of a general method for making dialkyl hydroxymethylphosphonates. An 0-tetra-hydropyranyl derivative also has been made from dibutyl hydroxymethyl -phosphonate, and diethyl hydroxymethylphosphonate has been O-silylated with tert-butylchiorodimethylsilane and imidazole. Another useful congener in this series has been prepared by an Arbuzov reaction of methoxyethoxymethyl (HEM) chloride and triethyl phosphite. 

See also page 403, Section 6, for the synthesis of a,/3-unsaturated nitriles, carboxylic acids and derivatives, and page 1711, Section 4, for the homologation of carbonyl compounds. 

Reutrakul, V, and Kanghae, W. 1977. The synthesis of 0i, 3-unsaturated aldehydes by one-carbon homologation of carbonyl compounds. Tetrahedron Lett 18, 1377-1380. 

An interesting method for die synthesis of amines and the homologation of carbonyl compounds has been reported that utilizes the condensation of a lithiated formamidine with a carbonyl compound. 41 Typical examples are shown in Scheme 39. 

Homologation of Carbonyl Compounds from a Hetero8ubstltuted-a-selenoalkyl Metals... 

Table 4 Homologation of Carbonyls by Reaction with (PhS)2CHLi and Rearrangement with Cu ...

S2.1 I,l-Bis(seleno)alkyl metals as acyl anion equivalents 2.6.522 1,1-Sllyl-l -selenoalkyl metals as acyl anion equivalents 2.6 J3 Homologation of Carbonyl Compounds from a-Heterosubstituted-ai-selenoalkyl Metals 2.6J.4 Conclusion... 

Tebbe olefination One-carbon homologation of carbonyl compounds to afford the corresponding 1,1-disubstituted alkenes. 454... 

Binder, J., and Zbiral, E., A new procedure for homologation of carbonyl compounds to a-hydroxy-carboxylic esters by means of diethyl (trimethylsilylethoxymethyl)phosphonate. Tetrahedron Lett., 27, 5829, 1986. 

Diethyl 1-cyano-l-(dimethylamino)methylphosphonate has been used as the basis of one-carbon homologation of carbonyl compounds through the conversion of cyanoenamines into carboxylic acids. 475 7 ... 

The a,p-epoxy sulfoxides available using this protocol are important intermediates for several synthetic methodologies. For example, they give upon thermal rearrangement a, -unsaturated aldehydes and thus represent the pivotal intermediate in a two-step procedure for the one-carbon homologation of carbonyl compounds (Scheme 8). °... 

The anions derived from dihydro-1,3-oxazines have been nicely exploited as reagents to effect the two-carbon homologation of carbonyl compounds to provide a,3-unsaturated aldehydes, ketones and carboxylic acid derivatives. " For example, metallation of (77) followed by reaction with a wide variety of aldehydes and ketones provides adducts (78 Scheme 29 Although attempts to purify these adducts have been unsuccessful owing to facile retroaldolization, sequential reduction of (78) with sodium... 

Table 8 Two-carbon Homologation of Carbonyl Compounds to a,p-Unsaturated Aldehydes Using Dihydro-1,3-oxazines (77) (Scheme 29) ...

Looking carefully at the current literature we have learned that the ketene dithioacetal chemistry, widely used for one-carbon homologation of carbonyl compounds, has never been utilized for the construction of ulosonic acids [129]. Besides, ketene dithioacetals, readily available from ketones and aldehydes via the reaction with the ylides generated from substituted dithioacetals in the Peterson, Wittig or Homer-Emmons olefmation, have never been synthesized from lactones. 

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