DOI: 10.1002/adsc.200600400 A Simple Approach to Unsymmetric Atropoisomeric Bipyridine N,N’-Dioxides and Their Application in Enantioselective Allylation of Aldehydes Radim Hrdina, a Irena Valterovµ, b Jana Hodac ˇovµ, b Ivana Císar ˇovµ, c and Martin Kotora a,b, * a Department of Organic and Nuclear Chemistry, and Center for Structural and Synthetic Application of Transition Metal Complexes, Faculty of Science, Charles University, Hlavova 8, 128 43 Praha 2, Czech Republic Fax: (+ 420)-221-951-326; e-mail: kotora@natur.cuni.cz b Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo n. 2, 166 10 Praha 6, Czech Republic c Department of Inorganic Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 43 Prague 2, Czech Republic Received: August 8, 2006 Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/. Abstract: The [2 + 2 + 2] cyclotrimerization of 1-iso- quinolinyl-1,7-octadiyne with benzonitrile catalyzed by CpCo(CO) 2 opened a new pathway for a synthe- sis of unsymmetrical axially chiral bipyridine N,N’- dioxides. The N,N’-dioxide 3a was found to be highly catalytically active and enantioselective for the asymmetric allylation of aldehydes with allyltri- chlorosilane. The allylation took place with even 1% of the catalyst with an enantioselectivity up to 87% ee. Keywords: allylation; asymmetric catalysis; Lewis bases; microwave heating; organic catalysis Recently, asymmetric organocatalysis based either on Lewis acid or base interactions has been recognized as an efficient method for obtaining chiral compounds with high enantioselectivity. [1] Among the numerous examples of such molecules considerable attention has been attracted by amine N-oxides as powerful electron-pair donors. In this context, pyridine N- oxides and bipyridine N,N’-dioxides are of special in- terest in cases where the pyridine moiety is a part of a chiral scaffold. The electron-donating properties of pyridine N-oxides make them rather strong Lewis bases that are able to activate a number of reactants for a plethora of reactions such as allylation and alky- lation of carbonyl compounds, conjugated addition, aldol reaction, desymmetrization of epoxides, epoxi- dation, etc. [2] Although a number of various pyri- dine-, [3–8] bipyridine-, [9–11] and terpyridine-based li- gands [12] has been introduced into organic synthesis, there is a considerable synthetic demand for the de- velopment of new bipyridine-based organocatalysts. In this regard it would be attractive to develop a methodology that would allow the simple and fast synthesis of bipyridine N,N’-dioxides bearing various substituents in a close vicinity to the chiral scaffold. Recently, we have reported that the cobalt-cata- lyzed [2 + 2 + 2] cyclotrimerization of diynes with ni- triles is a suitable method for the preparation of po- tential pyridine-based organocatalysts with axial chir- ality. Unfortunately, the catalytic activity and enantio- selectivity of the corresponding chiral pyridine N- oxides was low: catalysis of the reaction of allyltri- chlorosilane or diethylzinc with benzaldehyde afford- ed after 3 days at 20 8C the corresponding products in 50%(20% ee)and72%(17% ee), respectively. [13] In the course of this cyclotrimerization research project aiming at the preparation of various heterocy- cles, we realized that [2 + 2 + 2] cyclotrimerization could be used for a modular synthesis of potentially atropoisomeric bipyridines from suitably substituted a-heteroaryl-a,w-diynes and nitriles (Scheme 1). [14] In this context, a plethora of unsymmetrically substituted bipyridines could be prepared by varying the substitu- ents R 1 and R 2 in the reactants. Such bipyridines would constitute an ideal starting material for the preparation of chiral bipyridine N,N’-dioxides, be- cause they could, besides having axial chirality, also exert additional steric and electronic effects caused by the unsymmetrical substitution pattern. In this work we focused on varying the substituent R 2 in the target compounds. As a starting compound for the cyclotrimerization reaction diyne 1 was chosen. It was prepared in 56% yield by Sonogashira coupling of 1-chloroisoquinoline with 1,7-octadiyne 822 # 2007 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim Adv.Synth.Catal. 2007, 349,822–826 COMMUNICATIONS