Lithiation of optically active oxazolinyloxiranes: configurational stability Renzo Luisi, Vito Capriati, Claudia Carlucci, Leonardo Degennaro and Saverio Florio * Dipartimento Farmaco-Chimico, Istituto di Chimica dei Composti OrganoMetallici “ICCOM”, Universita ` di Bari, Via E.Orabona 4, I-70126, Bari C.N.R., Sezione di Bari, Italy Received 2 July 2003; revised 30 July 2003; accepted 5 September 2003 Abstract—The a-lithiation reaction of optically active oxazolinyloxiranes has been investigated. The trapping reaction with D 2 O, MeI and acetone affording substituted oxazolinyloxiranes proved that the corresponding lithiated species are configurationally unstable. A stereoconvergency was observed in the case of lithiation – deuteration sequence of two oxazolinyloxiranes. q 2003 Elsevier Ltd. All rights reserved. 1. Introduction The synthesis of functionalized oxiranes using oxiranyl anion methodology is a useful and convenient synthetic procedure. 1 Numerous biologically important molecules containing the oxirane moiety in their skeleton have been prepared by such a methodology. 2 One major point in stereoselective syntheses based on this methodology is the configurational stability of the oxiranyl anions (as well as chemical stability). With stabilized oxiranyl anions the configurational stability is usually dependent upon the nature of the stabilizing group. 2d,3 Silyl, arylsulfonyl, dialkoxyphosphinyl, ethoxycarbonyl, cyano, trifluoromethyl, benzothiazolyl, oxazolinyl and unsa- turated organyl groups (aryl, vinyl and alkynyl) proved to be the most efficient oxiranyl anion stabilizing groups. All these groups facilitate the oxiranyl anion formation by promoting deprotonation and prolonging its solution lifetime so that capture with electrophiles is made possible. In previous papers 4 we reported that oxazolinyloxiranes can be easily deprotonated either a or b with respect to the oxazoline ring and the resulting oxazolinyloxiranyllithiums can be trapped with electrophiles. a-Lithiated oxazolinyloxiranes proved to be chemically and configurationally stable so that, under appropriate conditions, the trapping of the cis and trans lithiated derivatives with electrophiles took place with retention of configuration. A sort of stereoconvergency was observed with lithiated chiral oxazolinyloxiranes. a-Lithiated oxazolinyloxiranes showed a configurational stability that allowed the preparation of useful intermediates in organic synthesis such as a,b-epoxy-g-butyrolactones, and in highly enantioenriched form when an optically active oxazo- linyloxirane was used as the precursor. 4b In this paper we report on the reaction of a-lithiated oxiranes, prepared from chiral non-racemic oxazolinyloxiranes, with electrophiles, particular attention being addressed to the involved stereochemistry. 2. Result and discussion Our work started with the preparation of the required oxazolinyloxiranes. 5 Lithiation of (4S)-2-chloromethyl-4- isopropyl-2-oxazoline 1a, carried out with lithium diisopro- pylamide (LDA) in THF at 2988C, followed by lithium– titanium transmetalation performed with Ti(i-PrO) 4 , and acetone addition, provided at first the chlorohydrin 2a (not isolated), and later epoxide (1S,4 0 S)-3a upon treatment with NaOH in i-PrOH in a very high diastereoselectivity (dr .98:2). The same procedure using cyclohexanone as the carbonyl compound allowed the preparation of epoxide (2S,4 0 S)-3b (dr ¼ 97:3) (Scheme 1). 6 0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2003.09.018 Tetrahedron 59 (2003) 9707–9712 Scheme 1. Preparation of enantioenriched oxazolinyloxiranes 3a,b. Conditions: (i) (a) LDA/Ti(i-PrO) 4 , THF, 2988C, 10 min. (b) R 2 CvO. (ii) NaOH/i-PrOH. * Corresponding author. Tel.: þ39-080-5442749; fax: þ39-080-5442231; e-mail: florio@farmchim.uniba.it Keywords: oxazolines; oxiranes; lithiation; configuration; stereochemistry.