Methoxycarbonyl total synthesis

The parent TMM precursor (1), now commercially available, has played a pivotal role in the execution of many synthetic plans directed at natural and unnatural targets. Reaction of (1) with 2-(methoxycarbonyl)cyclohexenone (14, R=C02Me) in the presence of palladium acetate and triethyl phosphite produced the adduct (15) in near quantitative yield. This cycloadduct is a critical intermediate in the total synthesis of a hydroxykempenone (16), a component of the defensive substances secreted by termites (Scheme 2.5) [12]. In accord with a previous observation by Trost that unactivated 2-cyclohexenone reacts poorly with TMM-Pd [13], the substrate (14, R=Me) was essentially inert in the cycloaddition. 

Liu H. J., Chew S. Y., Yeh W. L. Facile Selective Diels-Alder Reactions of Chiral 5,5-Dimethyl-4,6-Methano-2-Methoxycarbonyl-2-Cyclohexenone. Application to the Total Synthesis of Qinghaosu. Youji Huaxue 1993 13 314 321 Keywords (-)-/f-pinene, asymmetric synthesis... 

A Pd-catalyzed alkoxycarbonylation of 2-chloropyridine 117 to ester 118 was reported in the synthesis of camptothecin analogs <97JOC6588>. Another Pd-catalyzed alkoxycarbonylation was the central feature in Hibino s total synthesis of oxopropaline G (121), a P-carboline isolated from Streptomyces sp G324 <98TL2341>. Triflate 119 was prepared from 2-foimyl-3-iodoindole in seven steps. The Pd-catalyzed alkoxycarbonylation of 119 provided the key intermediate, l-methoxycarbonyl-4-methylcarboline 120, which was then transformed to oxopropaline G (121) in four additional steps. 

Intramolecular nucleophilic ring opening of 4-methoxycarbonyl-l-azaphenanthrene 5,6-oxide (262) has been utilized in the total synthesis of eupolaramine (263).155... 

A general synthetic route toward the marine metabolite eunicellin diterpenes was developed by G.A. Molander and co-workers.The power of this method was demonstrated by the completion of the asymmetric total synthesis of deacetoxyalcyonin acetate. A tricyclic (3-keto ester intermediate was methylated in the y-position with complete diastereoselectivity using dianion chemistry and the crude product was subjected to the Krapcho decarboxylation. This was one of the rare cases when the transformation did not only remove the methoxycarbonyl group, but at the same time epimerized the newly formed stereocenter to yield a separable mixture of methyl ketones. 

The total synthesis (Scheme 25) of ( )-rhazinilam was achieved by viewing the alkaloid as a derivative of a 3-phenylpyrrole. Thus 2-methoxycarbonyl-4-(2-nitrophenyl)pyrrole was first synthesized and then the aliphatic portion of the molecule introduced by alkylation at the pyrrole nitrogen [ —>(111)] and the carbon skeleton completed by intramolecular Friedel-Crafts alkylation [— (112)] at the only available pyrrole a-position. 

Danishefsky etal. [61] reported an improved route to (20/ .J)-camptothe-cin in connection with their original total synthesis [60, 62-64], Reaction of tricyclic compound (14) with sodium hexamethyldisilazide and benzalde-hyde afforded a 90% yield of the benzylidene acid (15). A mechanism similar to a Stobbe condensation with participation of the methoxycarbonyl function on the pyridone ring is suggested for this reaction step. Ozonolysis of this compound (15) Scheme 2.2) afforded a 96% yield of the acid (16) which, upon esterification, provided (17) in 81% yield. Compound (17) is readily converted to (20/ S)-camptothecin. 

Marko, l.E. and Chesney, A. (1992) Towards the total synthesis of manzamines preparation and reactions of 2-methoxycarbonyl-l,3-butadienes and P-amino aldehydes, Synlett, 275-278. 

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