Reductive deformylation

Reductive deformylation of 71 then gave a 50% yield of pentanoate 72, which still required an additional carbon atom to obtain the required fragment. This homologation was then accomplished via reduction of ester 72 to the aldehyde, chain extension to the terminal dibromide, and conversion to the acetylene 73 (55%). Hydrozirconation followed by quenching with iodine afforded the desired fragment 74 in 67% yield. 

One route to o-nitrobenzyl ketones is by acylation of carbon nucleophiles by o-nitrophenylacetyl chloride. This reaction has been applied to such nucleophiles as diethyl malonatc[l], methyl acetoacetate[2], Meldrum s acid[3] and enamines[4]. The procedure given below for ethyl indole-2-acetate is a good example of this methodology. Acylation of u-nitrobenzyl anions, as illustrated by the reaction with diethyl oxalate in the classic Reissert procedure for preparing indolc-2-carboxylate esters[5], is another route to o-nitrobenzyl ketones. The o-nitrophenyl enamines generated in the first step of the Leimgruber-Batcho synthesis (see Section 2.1) are also potential substrates for C-acylation[6,7], Deformylation and reduction leads to 2-sub-stituted indoles. 

Garcia et al. has extended the Batcho-Leimgruber procedure to the synthesis of 2-substituted indoles. Treatment of 36 with o-fluorobenzoyl chloride 37, followed by in situ hydrolysis and deformylation gave ketone 38. Reduction of nitroarylketone 38 with sodium hydrosulfite then furnished indole 39. Similarly, bromoacetylation of 36 gave an acylenamine which was converted into the phthalimido derivative 40. Hydrolysis and deformylation gave phthalimidoketone 41 which underwent reductive cyclization to furnish indole 42. 

The pseudobenzylisoquinoline alkaloids are fairly widespread in nature, being found among members of Berberidaceae, Annonaceae, Fumariaceae, and Ranunculaceae. The biogenesis of the pseudobenzylisoquinoline alkaloids assumes their formation from protoberberinium salts by C-8—C-8a bond scission in a Baeyer-Villiger-type oxidative rearrangement to produce the enamides of type 73 and 74. These amides may be further biotransformed either to rugosinone (76) type alkaloids by hydrolytic N-deformylation followed by oxidation or to ledecorine (75) by enzymatic reduction. These transformations were corroborated by in vitro studies (80-82). It is suggested that enamide seco alkaloids may be precursors of aporphine alkaloids (80), on one hand, and of cularine alkaloids (77), on the other. 

Johnson has developed two linear approaches to synthesize the C-nor-D-homosteroid skeleton (Scheme 2.2). In his first approach [21], tetralone 19, obtained from reduction of 2,5-dimethoxynaphthalene, was used as the source of the C,D-rings. The B- and A-rings were constructed by sequential Robinson annulations (19 —> 20 —> 21). The Cl 1,12 olefin was then introduced to provide 22. Ozonolysis of 22 followed by an aldol reaction of the resulting dialdehyde gave 23. Subsequent deformylation and deoxygenation afforded the cyclopamine skeleton 24. 

Mithramycin shows a completely P-linked chain of D-conflgurated saccharides. This requires a totally different approach for the synthesis which is also done by application of the DBE method. The previously obtained disaccharide 180 is P-glycosylated with the monosaccharide precursor 176 to give the trisaccharide 185. After reductive debromination (Bu3SnH), an acid deformylation deblocked the C-3" position which is oxidized with pyridinium dichromate. Nucleophilic attack at the carbonyl group by methyl lithium affords a 1 1.2 mixture of 186 and 187 none of which is the desired compound [93]. Obviously, the methyl branch is formed exclusively in the axial way. 

Dehydrogenation of cydohexanes, cyclohexenes, cyclohexanols, cyclohexanones, alkanes Deformylation of aldehydes Oxidation of hydrocarbons, CO. NHj Reduction of nitrogen oxides... 

The core skeleton of geissoschizine, an important biosynthetic precursor to numerous polycyclic indole scaffolds, was the target of a nickel-catalyzed alkylative coupling strategy. Cyclization precursor 13 was prepared by ozonolysis and double reductive amination of cyclopentene 12 (Scheme 8.13) [35]. Nickeldeprotection/oxidation sequence followed, and chromatography led to complete inversion of the C3 stereocenter. A Fisher indole synthesis followed to afford ( )-deformyl-isogeissoschizine, the core skeleton of geissoschizine. 

The above classes of alkylative and reductive couplings have been applied in the synthesis of various classes of complex alkaloids, including an alkylative cyclization entry to deformyl isogeissoschizine and a reductive cyclization entry to 11-methoxy mitragynine pseudoindoxyl (Scheme 3-51). ... 

Since hydrolysis and decarboxylation of the malonate function under acidic conditions was precluded due to presence of acid sensitive groups in the molecule, the desired transformation was effected by selective reduction followed by base catalyzed deformylation of the resulting aldehyde. 

Figure 5. Reduction of 4-amino-2,6-dinitrotoluene (4Am-DNT) to 2,4-diamino-6-nitrotoluene (2,4DAm-NT) by non-ligninolytic cultures of R chrysosporium. The formylation of the amino group of 4Am-DNT led to 4-formamido-2,6-dinitrotoluene (4FAm-DNT). The latter is reduced to 2-amino-4-formamido-6-nitrotoluene (2Am4FAm-NT) which is subsequently deformylated.

---