Monomorine enantioselective syntheses

The concise enantioselective total synthesis of (+)-monomorine I, a 3,5-dialkyl-substituted indolizidine alkaloid, was completed by S. Blechert et al. using a sequential cross-metathesis double reductive cyclization strategy. The enedione substrate was prepared in two steps. The Stetter reaction between the masked equivalent of acrolein and butyl vinyl ketone was followed by a retro Diels-Alder reaction under flash vacuum pyrolysis (FVP) conditions. 

The synthesis of indolizidine 195B (450) has in general been the fortuitous result of indifferent diastereoselectivity in routes to its diastereomer monomorine I (427). The racemic alkaloid accompanied ( )-monomorine I, and sometimes other diastereomers, in several post-1985 syntheses (393,397,399,400,402,403). Enantioselective syntheses of 450 published during the period 1985-1993, most of them also producing 427, were discussed in Volume 44 of this treatise (2), while post-1993 enantioselective syntheses leading to mixtures of 427 and 450 were detailed in Section V.A of this chapter (404,410,413,415,419). A conference paper describing the synthesis of (+ )-450 and the C-5 epimer (+ )-595 was also highlighted in Volume 44 this work has subsequently been published with full experimental details (468). 

The Wacker-Tsuji oxidation has been applied in the synthesis of alkaloids as well. In an enantioselective total synthesis of (+)-monomorine 1, alkene 95 was oxidized to ketone 96, which was converted to (+)-monomorine I 97).6S> In addition, the synthesis of ABE tricyclic analogs of methyllycaconitine used a Wacker oxidation-aldol strategy to append the B ring to the AE fragment.7"... 

The indolizidine alkaloid (+ )-monomorine I (373), isolated from Pharaoh s ant Mono-morium pharaonis, is the first example of an indolizidine alkaloid found in the animal kingdom. One enantioselective total synthesis of 373 exploits an asymmetric cycloaddition of nitrone 370 to the chiral allylic ether 369, which is prepared from 349. The conversion of 349 to a tosylate followed by treatment with -propylmagnesium bromide in the presence of... 

A short synthesis of (-f)-monomorine (1562) by Maruoka and coworkers used the chiral phase-transfer catalyst (R)-1672 to mediate an enantioselective conjugate addition between enone 1673 and the imine-protected glycine ester 1674 (Scheme 213). In a remarkable one-pot reaction, the intermediate adduct 1675 was then treated with Hantzsch ester (diethyl 2,6-dimethyl-l,4-dihydropyridine-3,5-dicarboxylate) in mildly acidic medium, which brought about deprotection of the acetal and imine as well as a double reductive amination in which the dihydropyridine acted as the hydrogen transfer agent. The resulting indolizidine ester (—)-1676 was... 

Owing to its long-standing limitations, the Stetter reachon has been utilized in a limited number of syntheses (Figure 18.4). (3-Unsubstituted acceptors have been used en route to cts-jasmone and dihydrojasmone [57], roseophilin (81) [58], ( )-trons-sabinene hydrate [59], monomorine I [60], and haloperidol [61], while a doubly activated Michael acceptor was used to access an intermediate in the synthesis of atorvastatin [62]. Less reactive P substituted acceptors could be used intramolecularly in the syntheses of ( )-hirsutic acid C (82) [63], ( )-platensimycin (83) [64], and polycyclic ether arrays [65], as well as in the enantioselective formation of a spirocychc intermediate toward FD-838 (84) [66]. 

An enantioselective one-pot operation involving the phase-transfer Michael addition for the construction of an octahydroindolizine framework was applied to the synthesis of (+)-monomorine 112 (Scheme 4.26)." The... 

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