Premium
Regio‐ and Stereoselective Synthesis of Acetallic Tetrahydropyrans as Building Blocks for Natural Products Preparation, via a Tandem [4+3]‐Cycloaddition/Ozonolysis Process
Author(s) -
Montaña Ángel M.,
Corominas Albert,
Chesa Juan F.,
García Francisca,
FontBardia Mercè
Publication year - 2016
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201600590
Subject(s) - ozonolysis , cycloaddition , chemistry , stereocenter , regioselectivity , stereoselectivity , tandem , diene , combinatorial chemistry , organic chemistry , enantioselective synthesis , catalysis , materials science , natural rubber , composite material
A highly versatile synthetic pathway is presented for the preparation of polyfunctionalized acetallic tetrahydropyrans from conveniently substituted 1‐methoxy‐8‐oxabicyclo[3.2.1]oct‐6‐en‐3‐one derivatives, as intermediates in the total synthesis of natural and unnatural products with structural, functional and/or biological importance. This synthetic methodology involves two key steps: a [4 + 3] cycloaddition reaction between an oxyallyl cation and 2‐methoxyfuran as a diene, followed by oxidative and/or reductive ozonolysis of the cycloheptenone subunit. This sequence renders polyfunctionalized 2‐methoxytetrahydropyranic products capable of being easily opened under acidic conditions. The key steps, cycloaddition and subsequent ozonolysis were both fully studied under different reaction conditions and using several substrates in order to optimize yields and stereoselectivities and to study the scope of the methodology. It is noteworthy that both reactions proceed with high diastereoselectivity and, in the case of the oxidative ozonolysis, outstanding regioselectivity as well. A chemical library of 14 polyfunctionalized tetrahydrofurans, having five or seven stereocenters, has been prepared using the detailed approach.