Readily Available Pyridine- and Quinoline-N-Oxides as New Organocatalysts for the Enantioselective Allylation of Aromatic Aldehydes with Allyl(trichloro)silane LUCA PIGNATARO, 1 MAURIZIO BENAGLIA, 1 * MAURO CINQUINI, 1,2 FRANCO COZZI, 1,2 and GIUSEPPE CELENTANO 3 1 Dipartimento di Chimica Organica e Industriale, Universita’ di Milano, Milan, Italy 2 CNR-ISTM, Universita’ di Milano, Milan, Italy 3 Istituto di Chimica Organica della Facolta’ di Farmacia—Universita’ di Milano, Milan, Italy Dedicated to Professor Piero Salvadori, Pisa, on the occasion of his 70th birthday. ABSTRACT The straightforward synthesis of a series of enantiomerically pure pyri- dine- and quinoline-N-oxides and their use as new organocatalysts for the enantiose- lective allylation of aromatic aldehydes with allyl(trichloro)silane is reported. The catalysts were readily assembled by combining commercially available enantiopure diamines with heterocyclic carboxylic acid N-oxides. The obtained compounds showed moderate to good chemical efficiency (up to 73% chemical yield) and satisfactory stereoselectivity (up to 50% ee). Tentative models of stereoselection were proposed to account for the stereochemical outcome of the reaction and to explain how the structural features of the catalyst control the stereoselctivity. Chirality 17:396 – 403, 2005. A 2005 Wiley-Liss, Inc. KEY WORDS: organic catalysis; stereoselective catalysis; synthesis of homoallylic alcohols; enantiomerically pure N-oxides Enantioselective organic catalysis represents one of the more rapidly expanding fields of research in modern organic chemistry. A number of fundamental organic reac- tions that once required the use of metal-based, enantio- pure catalysts can now be performed, with equal degrees of chemical and stereochemical efficiency, exploiting sub- stoichiometric amounts of structurally simple organic molecules that often are more stable and cheaper than their organometallic equivalents. 1 The catalytic enantioselective allylation of aldehydes 2 provides a paradigmatic example of how an organometallic catalyst can be effectively replaced by a metal-free one. Previously promoted by chiral Lewis acids, 3 this reaction can currently be carried out in the presence of a variety of organic Lewis bases as catalysts. 4 Among these, a preminent position pertains to pyridine N-oxides as demonstrated by the work of Nakajima, 5a Hayashi, 5b and Koc ¸ovsky. 5c,6 In all of the examples reported, however, the high level of stereocontrol achieved was the result of an extensive optimization of the stereochemical features of the catalysts, the synthesis of which required long and tedious procedures (sometimes involving also a resolution step) that subtract most of the appeal associated with an approach based on the use of an organic catalyst. On these bases, we started a project aimed to the devel- opment of structurally more simple chiral heteroaromatic N-oxides as catalysts for the enantioselective allylation of aldehydes with allyl(trichloro)silane, and here we report some preliminary results that we obtained in this field. MATERIALS AND METHODS General 1 H-NMR spectra were recorded on Bruker instruments at 300 MHz in chloroform-d (CDCl 3 ) unless otherwise stated and were referenced to tetramethylsilane (TMS) at 0.00 ppm; 13 C-NMR spectra were recorded at 75 MHz and were referenced to 77.0 ppm in CDCl 3 . 13 C{ 1 H}-NMR spectra were obtained using Waltz decoupling and were exponentially multiplied to give 0.8-Hz line broadening before Fourier transformation. All two-dimensional experi- ments were acquired with a Bruker inverse 5-mm z-gradient probe. The 90j pulse widths were 9.2 and 13.1 msec for 1 H and 13 C, respectively. The gradient was shaped by a waveform generator and amplified by a Bruker B-AFPA-10 amplifier. A sinusoidal gradient of length 1 msec and recovery time of 0.1 msec was used. The 2D COSY spectra were recorded with a 1,024 Â 1,024 data matrix and 512 increments of 1 scan each, in magnitude mode, with a relaxation delay of 1.0 sec and using a 1:1 gradient combination, then processed with Contract grant sponsors: MIUR (Progetto Nazionale Stereoselezione in Sintesi Organica. Metodologie ed Applicazioni); CNR *Correspondence to: Maurizio Benaglia, Dipartimento di Chimica Organ- ica e Industriale, via C. Golgi 19, I-20133 Milano, Italy. E-mail: maurizo. benaglia@unimi.it Received for publication 4 March 2005; Accepted 11 April 2005 DOI: 10.1002/chir.20180 Published online in Wiley InterScience (www.interscience.wiley.com). A 2005 Wiley-Liss, Inc. CHIRALITY 17:396–403 (2005)