Rhodium-catalyzed asymmetric arylative ring opening of bicyclic hydrazines Ferruccio Bertolini, Franco Macchia and Mauro Pineschi * Dipartimento di Chimica Bioorganica e Biofarmacia, Universita ` di Pisa, Via Bonanno 33, 56126 Pisa, Italy Received 28 September 2006; revised 23 October 2006; accepted 27 October 2006 Abstract—The development of a novel asymmetric ring opening of bi- and polycyclic hydrazines with aryl organometallic reagents is presented. The application of this reaction to the most simple bicyclic hydrazine 1a gives a straightforward regio- and diastereo- selective access to synthetically useful trans 3,4-disubstituted hydrazinocyclopentenes in an enantioenriched form. Ó 2006 Elsevier Ltd. All rights reserved. Disubstituted cyclopentenes are versatile synthons for the construction of a variety of biologically interesting molecules, and several methodologies are suitable for their preparation. 1 In particular, 3,5-disubstituted hydrazino cyclopentenes, which are useful intermediates for the synthesis of heterocyclic components by elabora- tion of the hydrazine moiety, 2 can be obtained by stereo- selective ring opening of symmetrical bicyclic hydrazines. 3 Symmetrical bicyclic hydrazines, are funda- mental structures that have been known for a very long time and can be easily obtained from the hetero Diels– Alder reaction of cyclopentadiene with azodicarboxyl- ates. 4 Descriptions of a palladium-catalyzed hydroaryl- ation and a palladium-catalyzed reaction of allyl- and arylstannanes in ionic liquid to give 3,4-disubstituted hydrazinocyclopentenes are quite recent, but the ring- opened products were obtained invariably in a racemic form. 5 To the best of our knowledge, no example of asymmetric ring opening of bicyclic hydrazines with aryl organometallic reagents has been described so far. We recently reported a new copper-catalyzed ARO of sym- metrical bicyclic hydrazines of type 1 with hard alkyl metals to give 3-alkyl-4-hydrazino cyclopentene deriva- tives (Fig. 1). 6a Nevertheless, with our reaction protocol that make use of a copper–aminophosphine catalyst, 6b an effective arylation of bicyclic hydrazines with aryl organometallic reagents was not feasible. In order to address this problem we turned our attention to the use of a rhodium catalysts in combination with air and moisture tolerant arylboronic acids. The development of new asymmetric carbon–carbon bond formation by means of rhodium catalysis has attracted much attention in recent years. 7 In particular, spectacular advances have been made in the area of the asymmetric rhodium-catalyzed ring opening of 7-aza- and 7-oxanorbornene derivatives with aryl boronic acids by Lautens et al. 8 We herein report the development of a rhodium-cata- lyzed asymmetric arylation of symmetrical bicyclic hydrazines with aryl organometallic reagents to give a new regioselective and diastereoselective access to aryl- ated hydrazinocyclopentenes in an enantioenriched form. A preliminary screening of the reaction with phenyl- boronic acid showed that the use of a rhodium-catalyst 0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2006.10.153 * Corresponding author. Tel.: +39 0502 219 668; fax: +39 0502 219 660; e-mail: pineschi@farm.unipi.it N N R 1 1a, R 1 =R 1 =COOEt 1b, [R 1 , R 1 ]=(CO) 2 -NPh R 1 N N O O 1c 1b or 1c Cu(I)/phosphoramidite AlR 3 , CH 2 Cl 2 R N NH R 1 R 1 up to 86% ee with R=Me (Ref. 6) Figure 1. Bicyclic hydrazines of type 1 used as starting material for new asymmetric arylation. Tetrahedron Letters 47 (2006) 9173–9176