Synthesis of conduramines from N-tert-butoxycarbonylpyrrole

Article abstract of DOI:10.1021/jo971907r

Two related synthetic strategies were devised to convert the Diels- Alder adduct 3c of Boc-pyrrole and p-toluenesulfonylacetylene into various racemic and optically pure conduramines. One process consists of the regio- and stereoselective hydroxylation of 3c to the tri- and dihydroxylated azabicyclo-[2.2.1]heptane derivatives 10b (Scheme 2) and the exo-endo mixture 13-14 (Scheme 3). Anionic fragmentation of 10b (methylmagnesium bromide) and of the 13-14 sulfone mixture (lithium bis-(trimethylsilyl)amide) generated the corresponding tri- and dihyroxylated aminocyclohexenes 17 and 16 (Scheme 3). Compound 17 is an aminocyclitol with a stereochemistry and partial aminotriol sequence identical to that found in neoinosamine. Compound 16 served as a source of the protected and free aminodiols 35b and 35a (Scheme 6), which were stereospecifically epoxidized to 36 (Scheme 6) and 40 (Scheme 7). Phenylselenide cleavage of these epoxides provided 37 (Scheme 6) and 41a (Scheme 7), which after selenoxide cycloelimination and protecting group manipulation were converted into (±)-conduramine C-1 (39a, Scheme 6) and the previously unreported, all-cis-conduramine D-1 (43a, Scheme 7). In a second process, anionic fragmentation of the bicyclic system is effected prior to introduction of the hydroxyl groups, as exemplified by the high-yielding conversion of the exo-endo mixture of azabicycloheptenes 11 and 12 into the aminocyclohexadiene 15 (Scheme 3). Osmate catalyzed cis-dihydroxylation of the derived bis-Boc derivative 20 (Scheme 4) led stereospecifically to the α-cis-diol 21 which was transformed into (±)-conduramine A-1 (27a) and its tetraacetyl derivative 27b via the epoxy compound 24. On the other hand, peracid oxidation of the diene 15 gave the β-epoxide 28 (Scheme 5) which was cleaved to the trans-diol 29 with aqueous sulfuric acid. This diol was converted into (±)-conduramine F-1 (34a) and its tetraacetyl derivative (34b) by a reaction sequence similar to that used for the other conduramine syntheses. Fractional crystallization of the diastereomeric mixture of Michael adducts obtained from (±)-3c and (-)-methyl lactate gave (-)-44a and (-)-45a both in ≤47% yield (Scheme 8). Both the carboxylic acid (+)-44b and the primary alcohol (+)-46 derived from (-)-44a were converted into (-)-3c with excess methylmagnesium bromide (ca. 40% overall yield). In the same way (-)-45a was transformed into optically pure (+)-3c. (-)-3c and (+)-3c were then converted into (-)-conduramine C-1 [(-)-39a] and (+)-conduramine D-1 [(+)-43a] by procedures identical to those used for the racemic compounds.