Highly Enantioselective Cross‐Aldol Reactions of Acetaldehyde Mediated by a Dual Catalytic System Operating under Site Isolation. Issue 41 (28th August 2014)

• Record Type: Journal Article
• Authors: Fan, Xinyuan; Rodríguez‐Escrich, Carles; Wang, Shoulei; Sayalero, Sonia; Pericàs, Miquel A.
• Is Part Of: Chemistry. Volume 20:Issue 41(2014)
• Page Start: 13089
• Page End: 13093
• Publication Date: 2014-08-28
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201404215
• Languages: English
• ISSNs: 0947-6539

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Polystyrene‐supported (PS) diarylprolinol catalysts <bold>1 a</bold> (Ar=phenyl) and <bold>1 b</bold> (Ar=3, 5‐bis(trifluoromethyl)phenyl) have been developed. Operating under site‐isolation conditions, PS‐<bold>1 a</bold>/<bold>1 b</bold> worked compatibly with PS‐bound sulfonic acid catalyst <bold>2</bold> to promote deoligomerization of paraldehyde and subsequent cross‐aldol reactions of the resulting acetaldehyde in one pot, affording aldol products in high yields with excellent enantioselectivities. The effect of water on the performance of the catalytic system has been studied and its optimal amount (0.5 equiv) has been determined. The dual catalytic system (<bold>1</bold>/<bold>2</bold>) allows repeated recycling and reuse (10 cycles). The potential of this methodology is demonstrated by a two‐step synthesis of a phenoperidine analogue (68 % overall yield; 98 % <italic>ee</italic>) and by the preparation of highly enantioenriched 1, 3‐diols <bold>4</bold> and 3‐methylamino‐1‐arylpropanols <bold>5</bold>, key intermediates in the synthesis of a variety of druglike structures.</p> </abstract>