One Carbon Homologation Reactions

Cyclopropylmagnesium carbenoids (75) generated by treatment of a-chlorosulfoxide (74) with /-PrMgCl have been shown to insert into the C-C bond of /3-aryl carbonyl compounds (Scheme 10). This insertion results from the reaction between (75) (g) and the enolate of the carbonyl compound (76) and thus corresponds to a valuable one-carbon homologation reaction or a ring-expansion reaction, as illustrated by the isolation of (77), from cyclic starting material. The insertion process proceeds in a... 

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... 

Dienes can be obtained from silylallenes by protodesilylation using boron trifluo-ride-acetic acid complex (equation 29)62. Since silylallenes can be obtained by the reaction of propargyl acetate with cuprous reagent derived from chloromethyltrimethylsilane, this reaction sequence constitutes conversion of propargylic acetate to butadiene through one carbon homologation. 

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. 

The formation of a-diazoketones from carboxylic acids (via the acyl chloride or an anhydride) and the subsequent Wolff Rearrangement in the presence of nucleophiles results in a one-carbon homologation of carboxylic acids. This reaction sequence. 

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. 

Benzyl acetates react with trimethylsilane and CO in the presence of Co2(CO)8 as catalyst to give P-phenethyl alcohols by a one-carbon homologation. The active catalyst is assumed to be (CH3)3SiCo(CO)4. The reaction proceeds under CO at atmospheric pressure at 25°. It fails with benzyl alcohol itself, but is successful with benzyl formate and benzyl methyl ether.5... 

Transition-metal-catalyzed carbonylation reactions are useful one-carbon homologation techniques in organic synthesis, involving industrially important processes, for example, Fisher-Tropsch reaction, Monsanto acetic acid process, and hydroformylation (oxo reaction) [25]. 

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. 

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. 

Homologation is the one-carbon extension reaction of organic compounds such as alcohols and carboxylic esters, and is very important. Cobalt, rhodium, and ruthenium complexes are known to be efficient catalysts. Methanol and methyl ester can be converted to ethanol and ethyl ester, respectively, using Ru/F [28] and Ru/Co [29] catalysts (Eq. 11.9). 

---