The sterospecific total synthesis of dl-lycopodine

Stork, Gilbert; Kretchmer, Richard A.; Schlessinger, R. H.

doi:10.1021/ja01008a042

Cited by 96 publications

(44 citation statements)

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“…Numerous syntheses of complex natural products [1] crucially rely on diastereoselectivity of the conjugate additions, as illustrated by the stereoselective synthetic step in our cortisone synthesis (Scheme 1). [2] Scheme 2 illustrates the simplest, textbook examples of high diastereoselectivities.…”

Section: Introductionmentioning

confidence: 99%

Density Functional Studies on Conjugate Addition of (Me2CuLi)2 to Cyclohexenone: Stereoselectivity and Rate-Determining Step

Mori

Nakamura

1999

Chem. Eur. J.

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The reaction pathway of the conjugate addition of a dimeric cuprate (Me 2 CuLi) 2 to 2-cyclohexenone has been studied by means of the B3LYP hybrid density functional method, and intermediates and transition structures (TSs) on the potential surface of the reaction have been determined. A lithium/carbonyl coordination complex (CPli), a copper/olefin complex retaining a closed cuprate structure (CPcl), a copper/olefin complex with an open cuprate structure (CPop), and the TS of CÀC bond formation (TScc) have been located along the gas-phase pathway leading to the conjugate addition product (PD). We studied two diastereoisomeric pathways, and found that the pathway that results in the axial placement of the nucleophilic methyl group in the product was favored throughout the course of the reaction, except in the product complex. Thus, the stereoselectivity of the conjugate addition to cyclohexenone originates from the stereochemical preference of the final, ratelimiting C À C bond formation stage that mainly reflects the steric factors in the formation of 3-methylcyclohexanone enolate in its half-chair form (TSccax).Comparison of the calculated and experimental values for 13 C NMR chemical shift and kinetic isotope effects strongly suggests that the copper/olefin complex of the CPop structural type is the reactive intermediate that directly forms the product. Thus, the open complex CPop, rather than the closed complex CPcl hitherto considered, is a direct precursor of the product and crucial for the stereoselectivity of the conjugate addition. On the basis of theory and experiments, transition-state models for the conjugate addition to substituted cyclohexenones are provided.

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Section: Introductionmentioning

confidence: 99%

Density Functional Studies on Conjugate Addition of (Me2CuLi)2 to Cyclohexenone: Stereoselectivity and Rate-Determining Step

Mori

Nakamura

1999

Chem. Eur. J.

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“…The isomünchnone cycloadduct 14 was formed from the Rh(II)-catalyzed reaction of diazo imide 13 and was found to be the precursor of the key Stork intermediate 16 (via 14) [46].…”

Section: Methodsmentioning

confidence: 99%

Tandem Methodology for Heterocyclic Synthesis

Padwa

2005

ChemInform

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Tandem methodology for heterocyclic synthesis represents a powerful approach for the rapid buildup of molecular complexity from potentially simple starting materials. Work from our laboratory has shown that the rhodium(II)-catalyzed cyclization cascade of α-diazo imides represents an effective method for the synthesis of a variety of heterocyclic systems. As an extension of these studies, we became interested in using a linked Pummerer/N-acyliminium ion cyclization sequence since we felt that this combination offers unique opportunities for the assemblage of complex target molecules. A synthetic method that combines transformations of different reaction types significantly broadens the scope of such procedures in synthetic chemistry. α-Thiocarbocations generated from the Pummerer reaction of β-phenylsulfinylmethyl-α,β-unsaturated amides can be intercepted by the adjacent amido group to produce transient amino-substituted furans which undergo subsequent Diels-Alder cycloadditions. Using this domino amido Pummerer/Diels-Alder cascade, we were able to assemble novel polycyclic systems in a single operation. The key step in the process involves the generation of a reactive N-acyliminium ion by fragmentation of an amino-substituted [4+2]-cycloadduct. The successful synthesis of a number of alkaloids by this sequence of reactions reveals the usefulness and importance of this unique domino cascade. Application of the process for the preparation of the stenoma alkaloid stenine was recently carried out in our laboratory.

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“…Central to this strategy was the expectation that the bicyclic iminium ion originating from 126 would exist in a chairlike conformation. [61][62][63] Indeed, cyclization of the aromatic ring onto the N-acyliminium ion center readily occurred from the axial position. [64][65][66] The rearranged product 127 was then converted into the key intermediate 128 previously used by Stork for the synthesis of (±)-lycopodine 129.…”

Section: (±)-Lycopodinementioning

confidence: 99%

“…[64][65][66] The rearranged product 127 was then converted into the key intermediate 128 previously used by Stork for the synthesis of (±)-lycopodine 129. 61,62 Scheme 25…”

Section: (±)-Lycopodinementioning

confidence: 99%

Use of nitrogen and oxygen dipole ylides for alkaloid synthesis

Padwa¹

2018

Arkivoc

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As highlighted in this mini review, a growing area of interest in organic synthesis involves the use of substituted azomethine and carbonyl ylides as 1,3-dipoles for the preparation of alkaloidal natural products. Cascade reactions proceeding by an intramolecular 1,3-dipolar cycloaddition of nitrogen and oxygen dipole ylides are of particular interest to the synthetic organic community because of the increase in molecular complexity involved and the high isolated yields.

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The sterospecific total synthesis of dl-lycopodine

Cited by 96 publications

References 0 publications

Density Functional Studies on Conjugate Addition of (Me2CuLi)2 to Cyclohexenone: Stereoselectivity and Rate-Determining Step

Density Functional Studies on Conjugate Addition of (Me2CuLi)2 to Cyclohexenone: Stereoselectivity and Rate-Determining Step

Tandem Methodology for Heterocyclic Synthesis

Use of nitrogen and oxygen dipole ylides for alkaloid synthesis

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