Tropane-Based Dispirocyclic Oxiranes and Spirocyclic Ketones

Andrii Gerasov; Rodion Boiko; Grygoriy Dolgonos; Aleksandr Mandzhulo; Alexander Shivanyuk; Volodymyr Fetyukhin; Oleg Lukin

doi:10.1055/s-0040-1719848

Synthesis, Table of Contents

Synthesis 2022; 54(03): 723-731
DOI: 10.1055/s-0040-1719848

paper

Tropane-Based Dispirocyclic Oxiranes and Spirocyclic Ketones

Andrii Gerasov

^aI.F. Lab Ltd., Representative of Life Chemicals Inc. in Ukraine, 5 Murmanska St., Kyiv, 02000, Ukraine

,

Rodion Boiko

^aI.F. Lab Ltd., Representative of Life Chemicals Inc. in Ukraine, 5 Murmanska St., Kyiv, 02000, Ukraine

,

Grygoriy Dolgonos

^aI.F. Lab Ltd., Representative of Life Chemicals Inc. in Ukraine, 5 Murmanska St., Kyiv, 02000, Ukraine

,

Aleksandr Mandzhulo

^aI.F. Lab Ltd., Representative of Life Chemicals Inc. in Ukraine, 5 Murmanska St., Kyiv, 02000, Ukraine

^bInstitute of Organic Chemistry, National Academy of Sciences of Ukraine, 5 Murmanska St., Kyiv, 02000, Ukraine

,

Alexander Shivanyuk∗

^aI.F. Lab Ltd., Representative of Life Chemicals Inc. in Ukraine, 5 Murmanska St., Kyiv, 02000, Ukraine

,

Volodymyr Fetyukhin

^aI.F. Lab Ltd., Representative of Life Chemicals Inc. in Ukraine, 5 Murmanska St., Kyiv, 02000, Ukraine

,

Oleg Lukin

^aI.F. Lab Ltd., Representative of Life Chemicals Inc. in Ukraine, 5 Murmanska St., Kyiv, 02000, Ukraine

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Abstract

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Abstract

The Prilezhaev epoxidation of N-Boc-protected 3-cyclobutylidenetropane 1a affords a 1:2 mixture of compounds 2a and 2b, in which tropane and cyclobutane fragments are spiro-connected to the oxirane ring in endo- and exo-fashion, respectively. The exo-isomer 2b is obtained in 89% yield and 97% selectivity via the dioxirane oxidation of 1a. BF₃-catalyzed isomerization of exo-oxirane 2b results in a 1:1 mixture of the spirocyclic ketones endo 3a and exo 3b containing spiro-connected tropane and cyclopentanone rings, while endo-epoxide 2a gives exclusively endo-ketone 3a. Prilezhaev and dioxirane epoxidations of N-Boc-protected 3-cyclopropylidenetropane 1b affords a mixture of endo- and exo-oxiranes 2c and 2d. Compounds 2c and 2d are not isolated in individual forms since they isomerize into a mixture of spirocyclic ketones endo 3c and exo 3d. Removal of the Boc groups from ketones 3a–d gives the corresponding hydrochlorides of aminoketones 4a–d in quantitative yields. Quantum chemical calculations predict that the rearrangement of endo-epoxides into the corresponding endo-ketones involving BF₃-containing intermediates has by 4.4–7.9 kcal/mol lower activation barriers than the respective conversion of the exo-epoxides into exo-ketones. The cyclopropyl-containing dispiroepoxides 2c and 2d are predicted to interconvert faster into the corresponding ketones compared to their less strained cyclobutyl counterparts 2a and 2b.

Key words

spirocycles - tropane - oxiranes - cyclopropanes - cyclobutanes - rearrangement - selectivity - theoretical calculations

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References

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