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Publisher: Taylor & Francis Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK Phosphorus, Sulfur, and Silicon and the Related Elements Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/gpss20 Highly Stereoselective Tandem Pummerer Reaction/-Hydroxy Imine Rearrangement of E.P. - Sulfinylenamines Pierfrancesco Bravo , Marcello Crucianelli , Alessandro Volonterio & Matteo Zanda a C.N.R. - C.S.S.O.N. Dipartimento di Chimica del Politecnico , via Mancinelli 7, I-20131 Milano, Italy b C.N.R. - C.S.S.O.N. Dipartimento di Chimica del Politecnico , via Mancinelli 7, I-20131 Milano, Italy c C.N.R. - C.S.S.O.N. Dipartimento di Chimica del Politecnico , via Mancinelli 7, I-20131 Milano, Italy d C.N.R. - C.S.S.O.N. Dipartimento di Chimica del Politecnico , via Mancinelli 7, I-20131 Milano, Italy Published online: 17 Mar 2008. To cite this article: Pierfrancesco Bravo , Marcello Crucianelli , Alessandro Volonterio & Matteo Zanda (1997) Highly Stereoselective Tandem Pummerer Reaction/-Hydroxy Imine Rearrangement of E.P. -Sulfinylenamines, Phosphorus, Sulfur, and Silicon and the Related Elements, 120:1, 353-354, DOI: 10.1080/10426509708545545 To link to this article: http://dx.doi.org/10.1080/10426509708545545 PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the Content) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub- licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions D o w n l o a d e d
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Phosphorus. Sulfur, and Silicon. 1997, Vol. 120 & 121, pp. 353-354 e 1997 OPA (Overseas Publishers Association) Reprints available directly from the publisher Amsterdam E.V. Published in The Netherlands Photocopying permitted by license only under license by Gordon and Breach Science Publishers Printed in Malaysia Highly Stereoselective Tandem Pummerer Reaction/ a-Hydroxy Imine Rearrangement of E.P. P-Sulfinylenamines PIERFRANCESCO BRAVO, MARCELLO CRUCIANELLl/ ALESSANDRO VOLONTERIO AND MATTEO ZANDA C.N.R. - C.S.S.O.N. Dipartimento di Chimica del Politecnico, via Mancinelli 7, 1-20131 Milano, Italy. f Dipartimento di Chimica, Ingegneria Chimica e Materiali, Universita di L'Aquila, Via Vetoio, 1-67010, Italy Abstract. The highly stereoselective tandem Pummerer reaction/a-hydroxy imine rearrangement of E.P. a-fluoroalkyl-p-sulfmylenamines affording chiral non-racemic fluoropyruvaldehydes iV.S-ketals is described. The synthesis of fluorosubstituted organic fine chemicals is an important goal, owing to the outstanding chemical and biomedicinal properties induced by the insertion of fluorine. However, the stereoselective synthesis of fiuoroorganic molecules represents a significant challenge for the chemist. We have recently reported the synthesis of enantiomerically pure <x- fluoroalkyl-p-sulfinylenamines 1, new useful fluorinated chiral templates. 1 Treatment of 1 with trifluoroacetic anhydride, followed by addition of silica gel or of an aqueous NaHCC>3 solution, gives rise to a stereoselective tandem Pummerer reaction/arylthio group migration, producing the corresponding fluoro pyruvaldehydes /V,S-ketals 2 in high enantiomeric excess (figure 1 and table I). 2 *t O NHR j NR ^ ? ' pTolS . STEP1 1 a '. Re ~ CFi j R ~ Cbz ^ a p r 1 !? . T? 1 r*k- r 3 -, t a . Kp Cr 3 ; K Cuz l b : R F = CF 3 ; R = H 2 b : R p = CF 3 ; R' = COCF l c : R p = CF 2 H;R = Cbz 2 C : Rp = CF 2 H; R' = Cbz 1 d : Rp = CF 2 C1; R = Cbz 2 d : Rp = CF 2 C1; R' = Cb; 3 FIG. 1. Key: (i) TFAA, THF, 0C, 1 min; (ii) NaHCO 3 5% or SiO 2 /H 2 O (see table 1), 0C, 10 min. 353 D o w n l o a d e d
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354 P. BRAVO, M. CRUCIANELLI, A. VOLONTERIO AND M. ZANDA TABLE 1. Stereoselective formation of fluoropyruvaldehydes A^-ketals 2 from sulfoxides 1. Enamine R F Product NaHCO 3 5%; e.e. (yield) SiO 2 thenH 2 Q; e.e. (yield) (R)-(Z)-la CF 3 (+)-(R)-2a 68% (85%) (5)-(Z)-la CF 3 (-)-(S)-2a 68 % (85 %) CF 3 (+)<R)-2b 67% (88%) CF 2 H (+)-(R)-2c 42 % (86 %) CF 2 H (+)-(^)-2c 6% (86%) (/?)-(Z)-ld CF 2 C1 (+)-(R)-2d not performed 74 % (49 %) not performed 73 % (71 %) 62% (58%) 8 % (56 %) 79 % (70 %) The formation of the intermediate imine 3 was confirmed by performing the reaction in a NMR tube. Indeed, addition of trifluoroacetic anhydride (1 equiv) to a THF-d 8 solution of enamine 1, resulted in the clean formation of 3, stable for several days at room temperature. In the light of these results, a reasonable mechanism for the stereoselective formation of the aldehydes 2 from 1 involves a Pummerer reaction (step 1), followed by an a- hydroxy imine rearrangement (step 2), both occurring with high stereoselection. H^olS^X^ A H OOCCFj 3 - CFjCOOH FIGURE 2 H3C JH The absolute stereochemistry of the aldehydes 2 has been determined by X-ray crystallographic analysis of the enantiomerically pure molecule 4, obtained by addition of CUMgCl to (/J)-2a and subsequent esterification with (+)-(5)-a-phenylpropionic acid (figure 3). CbzHN SpTol 4 FIGURE 3 REFERENCES 1. Arnone, A.; Bravo, P.; Capelli, S.; Meille, S. V.; Zanda, M; Cavicchio, G.; Crucianelli, M., J. Org. Chem., 61, 3375 (1996). 2. Bravo, P.; Crucianelli, M.; Fronza, G.; Zanda, M., Synlett, 249 (1996). D o w n l o a d e d