Communication www.rsc.org/chemcomm CHEMCOMM Addition of functional vinylzinc reagents to nitrones: synthesis of (E)-N-allylhydroxylamines and their rearrangement into (E)-O-allylhydroxylamines Shashi Urvish Pandya, Corinne Garçon, Pierre Y. Chavant, Sandrine Py and Yannick Vallée* LEDSS, UMR 5616, Université J. Fourier, BP53, F-38041 Grenoble CEDEX 9, France. E-mail: Yannick.Vallee@ujf-grenoble.fr Received (in Cambridge, UK) 18th May 2001, Accepted 26th July 2001 First published as an Advance Article on the web 4th September 2001 The vinylzinc reagents derived from hydrozirconation of alkynes and transmetallation add readily to nitrones to yield pure (E)-N-allylhydroxylamines; some of these rearrange into O-allylhydroxylamines. In the course of our studies on nitrones, 1 we became interested in obtaining (E)-allylic N-hydroxylamines by the addition of organometallic reagents onto nitrones. In the past, addition of organolithium or organomagnesium reagents onto CNN bonds 2 was studied to a much lesser extent than the corresponding addition onto carbonyl functions, the major reason being that imines are less prone to nucleophilic addition and more prone to deprotonation. In recent years, there has been a renewed interest in the addition of organometallics onto CNN double bonds because of both the availability of more selective organotransition reagents, and the use of more reactive CNN species. Among the latter, nitrones appear to be an interesting choice as precursors. They are reactive, readily available and stable. Indeed, recent work has dealt with the addition of alkyl, 3 allyl 4 and alkynyl 3,5 lithium, magnesium and zinc reagents onto nitrones. Comparatively fewer examples of the addition of vinylic organometallics to CNN bonds have been described. Imines do, however, react readily with vinylzinc compounds. 6 It has also been shown that vinylmagnesium bromide adds to tosyl imines. 7 Furthermore, it was demonstrated 8 that vinylmagne- sium bromide adds rapidly to nitrones. These results were extended to diastereoselective additions onto chiral nitrones 9 but the results were limited to the simplest ethenyl organo- metallic reagent. For our study, we needed adducts from g-functionalized, pure E, vinylmetallic species. Thus, we decided to prepare these reagents according to Wipf’s procedure: 10 hydrozirconation of alkynes followed by transmetallation to the (E)-vinylzinc species. We found that the resultant organometallic reagents add readily onto nitrones, under mild conditions, to give secondary N-hydroxylamines in good yields† (Scheme 1, Table 1). As expected, only the E configuration was observed in the double bond of all the products. Also, excellent conversions were obtained for the addition of the vinylzinc species derived from hex-1-yne onto a variety of nitrones 2. Steric hindrance in the nitrone (entry g, 39% conversion) is a limitation. The more hindered vinylzinc reagent derived from hex-3-yne led to incomplete conversion (entry h), and the formation of N- benzyl-N-(1-phenylpropyl)hydroxylamine (10%), resulting from ethylzinc addition, accompanied the allylic product 3h. Addition onto the chiral nitrone 2d led to moderate diaster- eoselectivity at 0 °C. Functionalized alkynes can also be used in this protocol. The pivalate-protected but-3-yn-1-ol led readily to 3i and 3j. In other examples however, the w-cyanoalkyne (entry k), the O-protected propynol 11 (entries l, m, n, o) and the Table 1 Preparation of N-allylhydroxylamines Alkyne 1 Nitrone 2 Conv. of Isolated Entry R 1 R 2 R 3 R 4 2 (%) a yield (%) a n-Bu H PhCH 2 Ph > 95 62 b n-Bu H p-CF 3 PhCH 2 Ph > 95 70 c n-Bu H p-CF 3 PhCH 2 Me > 95 58 d n-Bu H PhCH 2 > 95 83 de 72% e n-Bu H Ph p-MeO-Ph > 95 62 c f n-Bu H p-Tolyl Ph > 95 50 c g n-Bu H t-Bu Ph 39 29 c h Et Et PhCH 2 Ph 40 30 i PivO-(CH 2 ) 2 - H PhCH 2 Ph > 95 58 j PivO-(CH 2 ) 2 - H PhCH 2 i-Pr > 95 60 b k NC-(CH 2 ) 3 - H PhCH 2 Ph 75 5 b l TMSO-CH 2 - H PhCH 2 Ph 90 32 b m TMSO-CH 2 - H Ph p-MeO-Ph > 95 30 c n MeO-CH 2 - H PhCH 2 Ph 50 35 b o MeO-CH 2 - H Ph p-MeO-Ph > 95 40 c p (EtO) 2 CH- H PhCH 2 Ph 46 16 q Ph H PhCH 2 Ph 90 0 d a Estimated from NMR of the crude product. b A significant amount of alkynyl adduct was also isolated, see text. c Isolated as the isomeric form 4, see text. d Only alkynyl adduct, 50% yield. Scheme 1 Reagents and conditions:(a) Cp 2 ZrHCl, CH 2 Cl 2 , rt, 1 h; vacuum; Et 2 Zn, CH 2 Cl 2 , 265 to 0 °C; (b) CH 2 Cl 2 , 0 °C, 6 h. This journal is © The Royal Society of Chemistry 2001 1806 Chem. Commun., 2001, 1806–1807 DOI: 10.1039/b104427n Published on 04 September 2001. Downloaded by University of California - Irvine on 29/10/2014 15:53:50. View Article Online / Journal Homepage / Table of Contents for this issue