Towards a Flexible Strategy for the Synthesis of Enantiomerically Pure [2.2]Paracyclophane Derivatives: The Chemistry of 4-Tolylsulfinyl[2.2]paracyclophane

Abstract

The use of enantiomerically enriched 4-tolylsulfinyl[2.2]paracyclophane as a precursor to a variety of mono- and di­substituted [2.2]paracyclophane derivatives is described. The goal of our research is to develop a single general precursor that permits the synthesis of the most common [2.2]paracyclophane substitution patterns. The chemistry of two diastereoisomers of 4-tolylsulfinyl[2.2]paracyclophane has been explored and it facilitates the synthesis of enantiomerically enriched 4-substituted and 4,13-disubstituted [2.2]paracyclophanes. Directed lithiations result in an unusual cyclisation reaction. Whilst the tolyl group cannot realise our goal, the chemistry outlined acts as a successful ‘proof of concept­.’

Key words

asymmetric synthesis - cyclophanes - sulfoxides - enantiomeric resolution

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  Supporting Information contains X-ray crytallographic data, full experimental, and figures showing select NMR data.

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  CCDC-276960-276961 and CCDC-772176-772181 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: [phone]; or [e-mail].

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7

This argument was originally stated in reference 5. Chemists that have worked with [2.2]paracyclophane might argue that the greatest impediment to advancing this field is the mercurial nature of these molecules that can hinder even the most simple-looking syntheses.

33

The crystal appears to contain the tribromo product co-crystallised with the dibromo product in a 2:1 ratio. There are two independent molecules with different conforma­-tions. In both the occupancy of the Br(3) atom is 0.67.