Three-carbon homologation

Air-stable palladium(O) catalyst, [(Cy3P)2Pd(H)(H20)]BF4, catalyses carbonylation of propargylic alcohols to generate dienoic acids and esters (equation 167)286. Since propar-gyl alcohols are obtained from carbonyl compounds by acetyhde addition reactions, this sequence constitutes a three-carbon homologation. a-Allenic alcohols are converted to tt-vinylacrylic acids under similar conditions (equation 168)287. 

The acid portion of 1 was assembled by enantio-and diastereocontrolled addition of Z-crotyl borane to the aldehyde 8, following the Brown protocol. Hydroboration and oxidation led to 9, which was condensed with the allenyl silane 10 to give 11 with high diastereocontrol. Conversion of the alcohol to the iodide followed by three-carbon homologation by the Myers procedure then led to 1, which was cyclized with > 10 1 regio- and diasterocontrol to give 12. Ozonolysis and methylenation of the less hindered ketone then delivered 3. 

A. Dondoni, G. Fantin, and M. Fogagnolo, 2-Acetylthiazole as a three-carbon homologating reagent of aldehydes. Application toward the synthesis of amino hexoses from L-serinal, Tetrahedron Lett. 30 6063 (1989). 

Exaltolide. The key step in a new synthesis of exaltolidc (4) is the three-carbon homologation of a Grignard reagent (1) with /i-propiolactone (2) catalyzed by Cul. The product (3) is converted into 4 in two steps.1... 

Stowell, J. C. Three-carbon homologating agents. Chem. Rev. 1984, 84, 409—435. 

Reactions of Grignard reagents with oxetane lead to three-carbon homologation yields are often good, but 3-halogenopropanol may be a significant by-product [37] ... 

This three-carbon homologation was used in a synthesis of the diterpene (— )-aplysin-20 (4) from nerolidol (equation 1). ... 

The formation of carbon-carbon bonds by means of three carbon homologating agents (d synthons) can provide a useful and desirable methodology for the preparation of inter alia, a,/5- and )5,7-unsaturated aldehydes. 

TABLE 33. / ,y-Unsaturated aldehydes by three carbon homologation... 

The reactions of anion (56) proceed entirely at the 7-position with D2O, Me2S04, EtI, PrI, CeHial, C7H15I, CsHnI, PhClHiI and TMS-Cl, and in every case ( -alkenylboranes result. Alkylations proceed in high yields (90-96%) and buffered oxidation of the products gives aldehydes (90-95% overall), giving an efficient three-carbon homologation of alkyl iodides (equation 51). ... 

Just, G., Potvin, P. and Hakimelahi, G.H., 3-Diethylphosphonoacrolein diethylthioacetal anion (6 1, a reagent for the conversion of aldehydes to a.P-unsaturated ketene dithioacetals and three-carbon homologated a.P-unsaturated aldehydes. Can. J. Chem., 58, 2780, 1980. 

Conversion of olefins into esters. Brown1 has extended the one-carbon homologation of olefins with carbon monoxide and the three-carbon homologation of olefins with acrolein to a two-carbon homologation with ethyl bromoacetate. The olefin is converted into the trialkylborane in THF at 0° by addition of the calculated quantity of diborane in THF. An equimolecular quantity of ethyl bromoacetate is added, followed by an equimolecular quantity of potassium f-butoxide in t-butanol. The reaction is apparently complete immediately. Ethyl chloroacetate can also be used, but the reaction is somewhat slower and gives slightly lower yields. 

Leukotrienes. Prostaglandins and Related Compounds.- Examples of the use of the Wittig reaction in the synthesis of compounds related to arachidonic acid include an efficient synthesis of methyl arachidonate (148) by a three-carbon homologation sequence involving (3,3-diisopropoxy-propyl)triphenylphosphorane (149).91 Both diastereomers of trioxilin B3... 

Oxidative chain extension.- Reaci hydes and the Wittig reaction with .ul cordingly, three-carbon homologation o ably, the transformation is successful ii... 

Three-carbon homologation of aldehydes, and also of cyclic and acyclic ketones to form a/8-unsaturated aldehydes, can be performed by treating the carbonyl compounds with 3-methoxyallylidenetriphenylphosphorane (23) followed by in situ hydrolysis of the dienol ether (Scheme 53). ... 

A second three-carbon homologation procedure for conversion of a saturated aldehyde into an a/8-unsaturated aldehyde involves initial reaction with cyclo-propylmagnesium bromide, followed by heating the cyclopropyl derivative in dimethyl sulphoxide containing a trace amount of boron trifluoride (Scheme 54). ... 

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