One-carbon homologations aldehydes

Aldehydes.1 This Wittig-Horner reagent (available from Fluka) converts aldehydes or ketones into a,fi-unsaturated isocyanides, which can be hydrolyzed to the one-carbon homologated aldehyde. 

Although reaction of organozirconocene compounds fails with most organic electrophiles, treatment with sterically unhindered isocyanides, such as rcBuNC, is possible." Organometallic species 24 attacks nBuNC 25 to give isocyanide-insertion product 26, which is finally hydrolyzed to the one-carbon homologated aldehyde 6. 

One-carbon homologation. The products 3) obtained by reaction of 2 with alkyl halides can be converted under mild conditions lo one-carbon homologated aldehydes, carboxylic acids, or enol methyl ethers. 

The phosphorane derived from triphenylphosphine and chloromethyl methyl ether (MOM-Cl, carcinogenic) reacts with aldehydes or ketones to furnish the corresponding enol ethers. These on acid hydrolysis produce one-carbon homologated aldehydes or lead to the conversion of a keto into an aldehyde group, respectively. ... 

Vinyl zirconocene derivatives react also with sterically unhindered isocyanides, such as n-BuNC, to give the isocyanide-insertion products. Acidic hydrolysis leads to the corresponding one-carbon homologated aldehydes in good yields (Scheme 12.31) [41]. 

Darzens glycidic ester condensation generally involves the condensation of an aldehyde or ketone 2 with the enolate of an a-halo ester 1 which leads to an a,P-epoxy ester (a glycidic ester) (3). Thus the reaction adds two carbons to the electrophile however, the reaction has been primarily developed as a one-carbon homologation method. That is, subsequent to the condensation, the ester is saponified and decarboxylation ensues to give the corresponding aldehyde or ketone 5.2... 

Addition of a silyl substituent into a-position of the a-(benzotriazol-l-yl)alkyl ether brings additional possibilities. Thus, lithiation of silyl ether 770 followed by treatment with an aldehyde or ketone gives unstable P-hydroxy-a-silyl-a-(benzotriazol-l-yl)alkyl ether 771 that spontaneously eliminates silanol to give vinyl ether 772 (Scheme 121). Treatment with ZnBr2 followed by hydrolysis with a diluted acid removes both the benzotriazolyl and the methyl groups to furnish carboxylic acid 773. In this way, in a simple manner, aldehydes and ketones are converted to one-carbon homologated carboxylic acid <1996S1425>. 

One-carbon homologation of an aldehyde to dibromoolefin, which is then treated with n-BuLi to produce a terminal alkyne. 

An efficient process for one-carbon homologation to aldehydes is based on cyclic boronate esters.17 These can be prepared by hydroboration of an alkene with dibromobor-ane, followed by conversion of the dibromoborane to the cyclic ester. The homologation step is carried out by addition of methoxy(phenylthio)methyllithium to the boronate ester. The migration step is induced by mercuric ion. Use of enantioenriched boranes and boronates leads to products containing the groups of retained configuration.18... 

Third, chromium-based reagents prepared by reduction of 1,1-dihalo compounds with CrCl2 are suitable for the transformation of aldehydes to (i4)-iodoalkenes, (it)-alkenylsilanes, " and ( )-alkenylboronic esters with one-carbon homologation (Equation (8)). The amount of CrCl2 can be reduced to a catalytic amount by using manganese (or zinc) and MesSiCl. " ... 

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 . 

The Strecker synthesis is the one-carbon homologation of an aldehyde to the a-amino nitrile. Robert Cunico of Northern Illinois University in DeKalb reports (Tetrahedron Lett. 44 8025, 2003) a modified Strecker leading directly to the amide of the a-amino acid. 

A third scalable method for one-carbon homologation, the conversion of an ester 5 to the terminal alkyne 7, was reported (Tetrahedron Lett. 2004,45,5597) by Kevin Hinkle of GlaxoSmithKline in Research Triangle Park, NC. The ester is reduced with Dibal, the intermediate is quenched with methanol, and the solution of liberated aldehyde is treated with K,CO, and the reagent 6 according to the Ohira procedure. Weinreb esters also work well with this protocol. The conversion was reported to work in 72% yield starting with 27 g of 5. Note that 6 has a DSC exotherm at about 70"C, so caution should be exercised in handling it. 

Carbonylation with CO in the presence of H2 leads to aldehydes. Bernhard Breit of Albert-Ludwigs-Universitat, Freiburg, has found (Chem. Comm. 2004, 114) that conversion of an allylic alcohol to the o-diphenylphosphanylbenzoate 8 allows highly diastereoselective and regioselective Rh-mediated one-carbon homologation. 

A mild oxidative one-carbon homologation of aldehyde to amide has been reported.326... 

Similarly 1,1-difluoroalkenes 12) lead via fluoroacetylenes to the corresponding ynamines in 30-40 % overall yields based on the starting aldehydes 7 13) and the whole process amounts to a versatile one-carbon homologation. Even vinyl ynamines are available by this sequence (5, 6) ... 

OL-Hydroxy aldehydes. A new method for one-carbon homologation of ketones to a-hydroxy aldehydes involves Darzens condensation with chloromethyl phenyl sulfone to give an ex,p-epoxy sulfone followed by ring opening by hydroxide ion. The anhydrous potassium hydroxide obtained by controlled addition of water to potassium /-butoxide (8,... 

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. 

Archer and co-workers (103) have also employed the Snieckus oxidative pho-tocyclization in the key step of their synthesis of the 7//-pyrido[4,3-c]carbazole ring system (Scheme 40). Thus, a Wittig condensation between pyruvate 242 and pyridine 243 gave the unsaturated ester 244. Photocyclization gave the tetracyclic ester 245. Reduction and reaction with methyl isocyanate led to carbamate 247. Oxidation of alcohol 246 to aldehyde 248, followed by a standard one-carbon homologation, gave the desired ethyl derivative 249. These chemists also synthesized the 10-methoxyl derivative of each compound. 

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