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Synthesis of Tropinone & 2-CMT

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Lego:
Total Synthesis of (+)-Cocaine via Desymmetrization of a meso-Dialdehyde
Douglas M. Mans and William H. Pearson
Org. Lett.; 2004; ASAP Web Release Date: 19-Aug-2004
DOI:10.1021/ol048777a


Experimental procedures: http://pubs.acs.org/subscribe/journals/orlef7/suppinfo/ol048777a/ol048777asi20040810_021748.pdf
NMR spectra: http://pubs.acs.org/subscribe/journals/orlef7/suppinfo/ol048777a/ol048777asi20040810_021838.pdf

Abstract: The total synthesis of (+)-cocaine is described. An extension of the recently reported proline catalyzed intramolecular enol-exo-aldol reaction to a meso-dialdehyde provided the tropane ring skeleton directly with good enantiomeric excess. The meso-dialdehyde was prepared using a 2-azaallyllithium [3 + 2] cycloaddition to generate a cis-2,5-disubstituted pyrrolidine. Overall, the synthesis proceeded in 6.5% yield and 86% ee over 14 linear steps starting from commercially available 3-benzyloxy-1-propanol.






Scheme 1. Retrosynthesis of Cocaine


Scheme 2. Total Synthesis of (+)-Cocaine

Rhodium:
Cocain-Synthese aus Hyoscyamin. I. Darstellung von Tropinon-carbonsäure-estern
N. A. Preobrashenski, M. N. Schtschukina, R. A. Lapina
Chem. Ber. 69, 1615-1618 (1936) (https://www.thevespiary.org/rhodium/Rhodium/pdf/hyoscyamine2cocaine-1.pdf)
____ ___ __ _

Über ein Nebenalkaloid des Cocains, das Isatropylcocain
C. Liebermann
Chem. Ber. 21, 2342-2355 (1888) (https://www.thevespiary.org/rhodium/Rhodium/pdf/truxilline.liebermann1888.pdf)

Drug_Phreak:
I am very interested in these two "Cocaine Precursors from Hyoscyamine" papers. Could someone translate the experimental sections of them?

Rhodium:
Preobrashenski only describes the hydrolysis of Hyoscyamine to tropine and its oxidation to tropinone in very general terms with references to other articles, and the actual experimental part only details the carboxymethylation of tropinone with sodium and dimethylcarbonate (described more in detail by S. P. Findlay in his landmark article Concerning 2-Carbomethoxytropinone, see Post 488336 (Rhodium: "Synthesis of Tropinone & 2-CMT", Methods Discourse)).

The second article in my post above discusses ?/?-Truxillines and other cocaine-related alkaloids from Erythroxylon coca.

Drug_Phreak:
OK... thanks for the info. Good read. Is it possible to produce 2,5-Diethoxytetrahydrofuran from 2,5-Dimethoxytetrahydrofuran? I probed the search engine and didn't find anything on this.

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