Stereo- and Enantioselective Addition of Organolithiums to 2-Oxazolinylazetidines as a Synthetic Route to 2-Acylazetidines
作者： Pantaleo Musci , Marco Colella , Flavio Fanelli , Angela Altomare , Luisa Pisano
关键词: Double bond 、 Azetidine 、 Medicinal chemistry 、 Oxazolidine 、 Stereoselectivity 、 Oxazoline 、 Lone pair 、 Chemistry 、 Reactivity (chemistry) 、 Enantioselective synthesis
摘要: A new synthetic route to N-alkyl-2-acylazetidines was developed through a highly stereoselective addition of organolithiums N-alkyl-2‐oxazolinylazetidines followed by acidic hydrolysis the resulting oxazolidine intermediates. This study revealed an unusual reactivity C=N bond oxazoline group when reacted with in non-polar solvent such as toluene. The observed has been explained considering role nitrogen lone pair azetidine ring well oxazolinyl promoting complexation organolithium, thus ending up double bond. high level stereoselectivity this is supported DFT calculations and NMR investigations, model proposed for formation intermediates, that have isolated fully characterized. Upon conditions, moieties were readily converted into 2-acylazetidines. approach applied preparation enantioenriched 2-acylazetidines starting from chiral not racemic N‐alkyl-2‐oxazolinylazetidines.
frontiersin.org
harvard.edu
figshare.com
sci-hub.se 参考文章(37)
Leonardo Degennaro, Luisa Pisano, Giovanna Parisi, Rosmara Mansueto, Guy J. Clarkson, Michael Shipman, Renzo Luisi, Nitrogen Stereodynamics and Complexation Phenomena as Key Factors in the Deprotonative Dynamic Resolution of Alkylideneaziridines: A Spectroscopic and Computational Study Journal of Organic Chemistry. ,vol. 80, pp. 6411- 6418 ,(2015) , 10.1021/ACS.JOC.5B00848
Shrikant B. Kulkarni, Norman H. Cromwell, The synthesis of l-alkyl-2-benzoyl-4-methylazetidine. Configurational and conformational studies Journal of Heterocyclic Chemistry. ,vol. 14, pp. 981- 983 ,(1977) , 10.1002/JHET.5570140606
Vito Capriati, Leonardo Degennaro, Raffaele Favia, Saverio Florio, Renzo Luisi, Stereospecific β-Lithiation of Oxazolinyloxiranes: Synthesis of α,β-Epoxy-γ-butyrolactones Organic Letters. ,vol. 4, pp. 1551- 1554 ,(2002) , 10.1021/OL025781I
Renzo Luisi, Vito Capriati, Saverio Florio, Peppino Di Cunto, Biagia Musio, Synthesis and lithiation of oxazolinylaziridines: the N-substituent effect Tetrahedron. ,vol. 61, pp. 3251- 3260 ,(2005) , 10.1016/J.TET.2005.01.045
François Couty, Gwilherm Evano, Azetidines: New Tools for the Synthesis of Nitrogen Heterocycles Synlett. ,vol. 2009, pp. 3053- 3064 ,(2009) , 10.1055/S-0029-1218299
Ugo Azzena, Giovanna Dettori, Luisa Pisano, Biagia Musio, Renzo Luisi, BH3-Promoted Stereoselective β-Lithiation of N-Alkyl-2-phenylaziridines Journal of Organic Chemistry. ,vol. 76, pp. 2291- 2295 ,(2011) , 10.1021/JO102474U
Aleksandr V. Marenich, Christopher J. Cramer, Donald G. Truhlar, Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions. Journal of Physical Chemistry B. ,vol. 113, pp. 6378- 6396 ,(2009) , 10.1021/JP810292N
J.C. Arnould, J. Cossy, J.P. Pete, Reactivite photochimique des α-aminoenones: reactions de cyclisation et nouveau type de reaction dans les α-sulfonamido-cyclohexenones Tetrahedron. ,vol. 36, pp. 1585- 1592 ,(1980) , 10.1016/S0040-4020(01)83126-4
Leonardo Degennaro, Marina Zenzola, Piera Trinchera, Laura Carroccia, Arianna Giovine, Giuseppe Romanazzi, Aurelia Falcicchio, Renzo Luisi, Regioselective functionalization of 2-arylazetidines: evaluating the ortho-directing ability of the azetidinyl ring and the α-directing ability of the N-substituent Chemical Communications. ,vol. 50, pp. 1698- 1700 ,(2014) , 10.1039/C3CC48555B
Ann E. Weber, Dipeptidyl peptidase IV inhibitors for the treatment of diabetes. Journal of Medicinal Chemistry. ,vol. 47, pp. 4135- 4141 ,(2004) , 10.1021/JM030628V