Morphines asymmetric synthesis

Hong, C.Y, Kado, N., Overman, L.E. (1993) Asymmetric Synthesis of Either Enantiomer of Opium Alkaloids and Morphinans. Total Synthesis of (—)- and (-f)-Dihydrocodeinone and (—)- and (-F)-Morphine. Journal of the American Chemical Society, 115, 11028-11029. 

White, J.D., Hrnciar, R, Stappendeck, F. (1997) Asymmetric Synthesis of (-F)-Morphine. The Phenanthrene Route Revisited. Journal of Organic Chemistry, 62, 5250-5251. 

Somewhat more effective catalysts are obtained by replacing BINAP with TolBINAP, which is 2,2 -bis(di-p-tolylphosphino)-l,l -binaphthyl.4 The presently preferred catalysts are complexes of Ru(OCOCF3)2 with (R)- or (S)-TolBINAP, obtained by treatment of Ru(OAc)2TolBINAP with 2 equiv. of trifluoroacetic acid. Such catalysts promote hydrogenation of typical enamides in 98% ee and 98% yield. This reaction can be used to provide asymmetric synthesis of isoquinoline alkaloids as well as of morphinans used as substitutes for morphine. 

A study of the phenolic oxidative coupling reaction in the synthesis of morphine alkaloids. An approach to the asymmetric synthesis of codeine... 

Oxidative coupling of cis-3,N-bis(methoxycarbonyl)-N-norreticuline an approach to the asymmetric synthesis of morphine alkaloids Schwartz, Martin A. Pham, Phuong T. K. 

General asymmetric synthesis of morphine and its analogs via enantioselective hydrogenation... 

Hong CY, Kado N, Overman LE (1993) Asymmetric-synthesis of either enantiomer of opium-alkaloids and morphinans - total synthesis of (—)-dihydrocodeinone and (-1-)-dihydrocodeinone and (—)-morphine and (+)-morphine. J Am Chem Soc 115 11028-11029 Mulzer J, Dumer G, Trauner D (1996) Formal total synthesis of (—)-morphine by cuprate conjugate addition. Angew Chem hit Ed 35 2830-2832... 

White JD, Hmciar P, Stappenbeck F (1997) Asymmetric synthesis of (+)-morphine. The phenanthrene route revisited. J Org Chem 62 5250-5251... 

Fig. 48 Rodrigo-Assoud s asymmetric synthesis of a morphine-type indolinocodeine...

Hong, C. Y. Overman, L. E. "Preparation of Opium Alkaioids by Paiiadium Cataiyzed Bis-Cyclizations. Formai Totai Synthesis of Morphine" Tetrahedron Lett. 1994, 35, 3453, Aiso see Hong, C. Y. Kado, N. Overman, L. E. "Asymmetric Synthesis of Either Enantiomer of Opium Alkaloids and Morphinans. Total Synthesis of (-)- and (+)-Dihydrooodeinone and (-)- and (+)-Morphine" J. Am. Chem. Soc. 1993, 115,11028-11029. Heerdlng, E. A. Hong, C. Y. Kado, N. Look, G. C. Overman, L. E. "Simple Method for Controlling Stereoseleotion in Mannich Cyclization Reactions of Aldehydes" J. Org. Chem. 1993, 58, 6847-6948. 

Intramolecular Heck reactions for building up complex oxacyclic skeletons are a common theme in the synthesis of natural products. These reactions are exceptionally valuable for the installation of quaternary carbon stereocenters. In the morphine total syntheses by Overman <1994PAC1423> and Trost et al., intramolecular Heck reactions to form dihydrobenzofurans served as strategic key steps (Equation 138) <2005JA14785>. Asymmetric variants of intramolecular Heck reactions based on BINAP ligands to yield dihydrobenzofurans have also been investigated <1998T4579>. 

The Noyori asymmetric transfer hydrogenation was utilized in the synthesis of the chiral 1,2,3,4-tetrahydroisoquinolines by R.A. Sheldon et al. These compounds are important intermediates in the Rice and Beyerman routes to morphine. The "Rice imine" was exposed to a series of chiral Ru " complexes, which was prepared from r -arene-Ru " chloride dimeric complexes and A/-sulfonated 1,2-diphenylethylenediamines along with the azeotropic mixture of HCOOH/NEts. With the best catalyst the desired tetrahydroisoquinoline was isolated in 73% yield and the enantiomeric excess was 99%. 

A study directed at the total synthesis of (-)-codeine and (-)- morphine synthesis via a novel asymmetric intramolecular Diels-Alder reaction Costanzo, Michael John... 

Recently, palladium-catalyzed asymmetric allylic substitution of an activated cyclohexenol derivative has allowed two enantioselective syntheses of (—)-galantha-mine (75) (234,235). Both approaches rely on the enantioselective preparation of the same tricyclic intermediate, which is subsequently converted to the alkaloid via stereocontrolled transformations the most efficient of which comprised stereoselective allylic oxidation of the cyclohexene moiety (Scheme 5). The same methodology allowed the synthesis of (—)-codeine and (—)-morphine (236). The same group had earlier reported the synthesis of (-l-)-pancratistatin following a related strategy (237). Use of a tosylamide as the nucleophile in the displacement of an activated aryl-cyclohexenol derivative enabled the preparation of a chiral intermediate which... 

Asymmetric total synthesis of (—)-octahydro-l f-benzofuro[3,2- ]isoquinoline 149, a partial structure of morphine, a potent analgesic alkaloid, was accomplished using the ATH protocol (Scheme 30.28). The ketone 147... 

Hsin L-W, Chen C-W, Chang L-T. Asymmetric total synthesis of( ) octahydro-lHbenzojuro[3,2-e]isoquinoline, a partial structure of morphine. J. Chin. Chem. Soc. 2005 52 (2) 339 346. 

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