An efficient asymmetric synthesis of key intermediates in the synthesis of aphanorphine and eptazocine

Taylor, Stephen K.; Ivanović, Milica; Simons, Lloyd J.; Davis, Matthew

doi:10.1016/s0957-4166(03)00117-4

Cited by 26 publications

(7 citation statements)

References 26 publications

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“…Herein, we descript a chiral cobalt(II) complex of N,N′ -dioxide that catalyzes the enantioselective Michael addition of 1-acrylpyrazoles with SKIs. − The reaction delivered α-aryl-α-alkyl-α-propenamidenitriles in high enantioselectivities and good yields with 2.5 mol % catalyst loading. Furthermore, the nitriles were successfully transformed into chiral drugs and natural products as listed in Figure a, including ( S )-verapamil, − ( S )-E2025, − ( S )-sporochnol A, − and (+)-glutechimide, − and key enantiomeric rich intermediates for the efficient synthesis of (−)-aphanorphine, − (+)-epilaurene, , and ( R )-aminoglutethimide . Calculations gave a detailed understanding of the dispersion stabilization , in the enantioselectivtity-determining processes, where attractive π–π and σ–π interactions between the substrate and the chiral catalyst play a key role in influencing the reactivity and the stereoselectivity.…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Synthesis of Nitriles Containing a Quaternary Carbon Center by Michael Reactions of Silyl Ketene Imines with 1-Acrylpyrazoles

Chen

et al. 2021

J. Am. Chem. Soc.

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The enantioselective construction of quaternary carbon centers is a marked challenge in asymmetric catalysis research. It is extremely difficult when a chiral catalyst can not distinguish the facial selectivity of the substrate through bond interactions. Here we realized an enantioselective Michael reaction of silyl ketene imines to 1-acrylpyrazoles using a chiral N,N′-dioxide−Co(II) complex. The protocol is highly efficient for the construction of nitrile-, aryl-, and dialkyl-bearing carbon centers and has been successful applied in the divergent synthesis of pharmaceuticals and natural products. The through-space dispersion interactions between unbound silyl ketene imines and the 1-acrylpyrazole-bonded catalyst play a key role in facilitating the reactivity and the enantioselectivity of this process.

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Section: Introductionmentioning

confidence: 99%

Enantioselective Synthesis of Nitriles Containing a Quaternary Carbon Center by Michael Reactions of Silyl Ketene Imines with 1-Acrylpyrazoles

Chen

et al. 2021

J. Am. Chem. Soc.

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“…(–)‐Aphanorphine, first isolated from the fresh‐water blue‐green alga Aphanizomenon flos‐aquae ,1 incorporates a 3‐benzazepine scaffold that resembles benzomorphane analgesics such as pentazocine,2 morphine3 and eptazocine 4. This structural similarity has attracted considerable attention from the synthetic community, and a number of syntheses has been reported for aphanorphine since its isolation.…”

Section: Introductionmentioning

confidence: 99%

Concise Route to (–)‐ and (+)‐Aphanorphine

Medjahdi¹,

González-Gómez²,

Foubelo³

et al. 2011

Eur J Org Chem

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“…A 17-step asymmetric synthesis of (À)-Lingzhiol was reported for the first time by Prof. Yang 7 via Rh-catalysed [3+2] cycloaddition, which efficiently constructed two quaternary carbon centers in one step. Considering the nucleophilicity of the electron rich aromatic ring and relative position of the hydroxyl group in lactone, we envisioned that the carbon at 7 0 could be formed by epoxy-arene cyclization [8][9][10] as illustrated in Scheme 1. Consequently, the retrosynthetic analysis is depicted.…”

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confidence: 99%