Novel decarboxylation reaction

Step-Economical Synthesis of Clinprost and Analogs Utilizing a Novel Decarboxylation Reaction... 

Pre-association by a proton donor or electron acceptor can be a novel catalytic component in decarboxylation reactions. The mechanism is readily available in biochemical systems but is difficult to achieve in solution as the preassociation requires specific interactions. As instances are found, they provide important information on the mode of catalysis. 

Barton, D. H. R., Zard, S. Z. A novel radical decarboxylation reaction. Janssen Chim. Acta 1986,4, 3-9. 

Further examples illustrating the usefulness of this novel decarboxylation were developed by modifying the dienoate and pentadienyl groups (Scheme 16). Surprisingly, these reactions can be performed intramolecularly or intermolecularly. Screening different groups, such as alkenes, aromatics, cyclopropanes, alkynes, and alkanes, instead of dienoate or pentadienyl groups, demonstrated that all these moieties failed to decarboxylate. This shows that both the diene and pentadienyl systems are required for the novel decarboxylation (Fig. 9). 

Knorr reported the first pyrazole derivative in 1883. The reaction of phenyl hydrazine and ethylacetoacetate resulted in a novel stmcture identified in 1887 as l-phenyl-3-methy 1-5-pyrazolone 9. His interest in antipyretic compounds led him to test these derivatives for antipyretic activity which led to the discovery of antipyrine 10. He introduced the name pyrazole for these compounds to denote that the nucleus was derived from the pyrrole by replacement of a carbon with a nitrogen. He subsequnently prepared many pyrazole analogs, particularly compounds derived from the readily available phenyl hydrazine. The unsubstituted pyrazole wasn t prepared until 1889 by decarboxylation of liT-pyrazole-3,4,5-tricarboxylic acid. ... 

Novel asymmetric conjugate-type reactions have been accomplished with Cinchona alkaloid-derived chiral thioureas, including less traditional reactions such as asymmetric decarboxylation [71]. In the following discussion, asymmetric reactions involving nitro-olefms, aldehydes and enones, and imines will be highlighted (Fig. 5). 

Researchers at the University of Graz, in collaboration with scientists from DSM, have developed an elegant and novel approach to the synthesis of P-amino alcohols using two different enzymes in one pot (Scheme 2.35). For example, a threonine aldolase-catalyzed reaction was initially used, under reversible conditions, to prepare L-70 from glycine 69 and benzaldehyde 68. L-70 was then converted to (R)-71 by an irreversible decarboxylation catalyzed by L-tyrosine decarboxylase. In a second example, D/L-syn-70 was converted to (R)-71 using the two enzymes shown combined with a D-threonine aldolase in greater than 99% e. e. and 67% yield ]37, 38]. 

A novel system for the enantioconvergent decarboxylative protonation of racemic /3-kclo esters has been developed.48 The reaction tolerates a variety of substitution and functionality and delivers products of high enantiopurity in excellent yield. The enan-tioinduction in the observed protonated products is consistent with the intermediacy of an enolate that is intimately associated with a chiral Pd complex. 

This reaction is clearly analogous to that of NAD-IDHs, NADP-IDHs, and NAD-IMDHs. Early studies showed that the enzyme of S. cerevisiae was separated from the NAD-IDH and has a different pH optimum [33], The molecular mass of the enzyme is 48 kDa. These results suggest that NAD-HDH is a novel member of the P-decarboxylating dehydrogenase family. In spite of a number of biochemical and genetic studies, the gene encoding the enzyme has not been identified. 

A facile, one-pot synthesis of an alkylated tetrahydrofuranone intermediate was applied to the synthesis of a novel hexahydrofuro[3,4-6]furan derivative <83TL2335>. Reaction of methyl acrylate with methyl sodium benzilate in DMSO gave the intermediate 3-oxo ester carbanion, which was alkylated with allyl bromide to yield the tetrahydrofuranone derivative (408). Subsequent hydrolysis and decarboxylation of (408), followed by reduction with lithium tri-r-butoxyaluminum hydride gave compound (409), which with excess iodine and Na2C03 afforded an 85 15 mixture of the epimers (410a) and (410b) in 95% yield (Scheme 38). 

On the basis of this palladium-mediated Michael addition cyclization process, a novel two-step synthetic entry into functionalized furan derivatives 67 has also been devised (Scheme 28). Substitution of benzylidene (or alkyli-dene) malonates for their ethoxymethylene analog (65) as activating olefins gave rise to the formation of the corresponding 2-ethoxy-4-arylidene tetrahy-drofurans 66. An in situ addition of potassium ferf-buloxidc induced a decar-boxylative elimination reaction which was followed by an isomerization of the exocyclic double bond. The entire process successively involved a conjugate addition, a palladium-catalyzed cyclization-coupling reaction, a base-induced eliminative decarboxylation, and finally, a double bond isomerization [73]. 

The combretastatins are a group of antimitotic agents isolated from the bark of the South African tree Combretum caffrum. A novel and highly stereoselective total synthesis of both the c/s and trans isomers of combretastatin A-4 was developed by J.A. Hadfield and co-workers.The (Z)-stereoisomer was prepared using the Perkin reaction as the key step in which 3,4,5-trimethoxyphenylacetic acid and 3-hydroxy-4-methoxbenzaldehyde was heated with triethylamine and acetic anhydride at reflux for several hours. The a,p-unsaturated acid was isolated in good yield after acidification and had the expected ( ) stereochemistry. Decarboxylation of this acid was effected by heating it with copper powder in quinoline to afford the natural product (Z)-combretastatin A-4. 

---