Synthesis 2020; 52(07): 1015-1024
DOI: 10.1055/s-0039-1691560
paper
© Georg Thieme Verlag Stuttgart · New York

Selective Synthesis of exo-Spiro[2′,2′-difluorocyclopropane-3′,2′-tropanes]

Andrii Gerasov
a  Life Chemicals Inc., Murmanska st. 5, Kyiv 02660, Ukraine   Email: A.Shivanyuk@lifechemicals.com
,
Grygoriy A. Dolgonos
b  Institute of Chemistry, University of Graz, Heinrichstraße 28/IV, 8010 Graz, Austria
,
Aleksandr Yu. Mandzhulo
a  Life Chemicals Inc., Murmanska st. 5, Kyiv 02660, Ukraine   Email: A.Shivanyuk@lifechemicals.com
c  Institute of Organic Chemistry, National Academy of Sciences of Ukraine, 5 Murmanska St., Kyiv 02660, Ukraine
,
Alexey Ryabitsky
a  Life Chemicals Inc., Murmanska st. 5, Kyiv 02660, Ukraine   Email: A.Shivanyuk@lifechemicals.com
,
Volodymyr Fetyukhin
a  Life Chemicals Inc., Murmanska st. 5, Kyiv 02660, Ukraine   Email: A.Shivanyuk@lifechemicals.com
,
Oleg Lukin
a  Life Chemicals Inc., Murmanska st. 5, Kyiv 02660, Ukraine   Email: A.Shivanyuk@lifechemicals.com
,
Alexander Shivanyuk
a  Life Chemicals Inc., Murmanska st. 5, Kyiv 02660, Ukraine   Email: A.Shivanyuk@lifechemicals.com
d  The Institute of High Technologies, Taras Shevchenko National University of Kyiv, 4 Glushkov st.5, Kyiv 03187, Ukraine
› Author Affiliations
Further Information

Publication History

Received: 18 November 2019

Accepted after revision: 11 December 2019

Publication Date:
02 January 2020 (online)


Abstract

Conformationally restrained exo-isomers of N-Boc-protected spiro[2′,2′-difluorocyclopropane-3′,2′-tropanes] were synthesized in 62–83% yield via absolutely diastereoselective cycloaddition of CF2, generated in situ from Me3SiCF3/NaI in refluxing THF, to double bonds of 3-alkylidenetropanes. Standard removal of Boc protecting groups afforded corresponding exo-spiro[2′,2′-difluorocyclopropane-3′,2′-tropane] hydrochlorides in 82–94% yields. DFT and CCSD(T) calculations revealed that the observed exo-selectivity of difluorocarbene addition is likely to be caused by a lower activation barrier of the exo-difluorocyclopropanation compared to the endo-reaction.

Supporting Information

 
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