SPOTLIGHT ██2773 SYNLETT Oxaziridinesspotlight Spotlight 452 Compiled by Laura Buglioni This feature focuses on a re- agent chosen by a postgradu- Laura Buglioni was born in Camerino (Italy) and studied Chemistry ate, highlighting the uses and and Advanced Chemical Methodologies at the University of Cameri- preparation of the reagent in no. She received her M.Sc. degree in 2011. Currently she is working as a doctoral student under the supervision of Professor Carsten current research Bolm at RWTH Aachen University (Germany). Her research inter- est is focused on the synthesis and reactivity of sulfoximines and sulfilimines. RWTH Aachen University, Institute of Organic Chemistry, Landoltweg 1, 52074 Aachen, Germany E-mail: [email protected] Introduction amples have been selected in order to provide an overview of the recent synthetic achievements. An oxaziridine is a strained, three-membered ring, con- R1NHNHPG sisting of weakly bound carbon, nitrogen, and oxygen at- R O O C oms. This heterocycle is synthesized by oxidation of the 1 R1NH N PG R 2 X corresponding imine, most commonly with m-chloroper- Ar 1 benzoic acid. Also, reagents such as t-butyl hydroperox- R O X Ar 1 C N ide and urea hydrogen peroxide complex can be used. R PG OR S Oxaziridines are very reactive due to the presence of three R1 R2 R2 R1 different atoms with different electronegativities. They O 1 R M O S can transfer the nitrogen or the oxygen atom and can un- R1 R2 R2 dergo [3+2] cycloadditions. The high reactivity has been R1 R1NHPG applied in many transformations with a wide range of re- OH actants, such as sulfides, organometallic reagents, amines, Scheme 1 Reactivity of oxaziridines and silyl enol ethers (Scheme 1).2 In this article, some ex- Abstracts (A) Intramolecular Amination: N-Sulfonyl oxaziridines 1 have recently been used in the activation OH 3 of C(sp )–H bonds in an intramolecular aminohydroxylation reac- NBs tion catalyzed by copper(II) salts. Surprisingly, rather than donation O NBs CuCl (2 mol%) 2 Ar an oxygen atom, a new C–N bond is formed in a highly regioselec- LiCl (4 mol%) NaBH(OAc)3 NBs H + tive manner. The proposed mechanism involves the abstraction of acetone HCl, THF O Ar the proton in the δ-position leading to the formation of a six-mem- Ar 3 up to 87% yield bered transition state. 1 NHBs Ar (B) Dynamic Kinetic Asymmetric Hydroxylation: In the presence of a chiral nickel(II) complex, oxaziridine 2 could O perform the α-hydroxylation of racemic malonates. The attack of 2 N This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. S occurs preferentially on the si face of the malonate, affording the O2 3 H R 2 HO R3 products in excellent enantioselectivities and yields. This methodo- L = O logy was extended to the synthesis of (R)-bicalutamide, an important 1 2 II O O R O2C CO2R L, Ni R1O C CO R2 anti-androgen drug used in the treatment of prostate cancer.4 2 2 N N up to 93% yield up to 98% ee Ph Ph SYNLETT 2013, 24, 2773–2774 Advanced online publication: 14.10.20130936-52141437-2096 DOI: 10.1055/s-0033-1338988; Art ID: ST-2013-V0459-V © Georg Thieme Verlag Stuttgart · New York 2774 L. Buglioni SPOTLIGHT (C) [3+2] Cycloaddition: N Oxaziridines easily undergo [3+2] cycloaddition with imines, ni- Ph 5 N triles, alkenes, and alkynes. Recently, this transformation catalyzed Ph N OTBS Ph by chiral N-heterocyclic carbenes was developed with ketenes and – O BF4 O oxaziridine 3, affording oxazolin-4-ones in moderate to good yields O (10 mol%) 6 C + NTs and excellent enantioselectivities. NTs Et Ar Cs CO (10 mol%) Ph Ar Ph Et 2 3 O 3 THF, r.t. up to 78% yield up to 99% ee cis/trans up to 16:1 (D) Oxidation of C–H Bonds: O Cy N A copper(I)-catalyzed intramolecular oxidation of C–H bonds was [Cu(PPh3)Cl]4 developed starting from the oxaziridine 4 to selectively give the cor- O Ar Ar THF, reflux OH responding allylic alcohol in moderate to good yields. The proposed 4 mechanism involves the formation of a copper-bound radical anion up to 75% yield arising from a single electron transfer, followed by hydrogen atom abstraction.7 (E) Asymmetric Oxyamination: Fe(NTf2)2 (10 mol%) Chiral iron(II) complexes have been showed to catalyze reactions O NNs L (20 mol%) Ar O between alkenes and N-nosyl oxaziridines 5, affording the corre- R + H Ar PhH N sponding substituted oxazolidines with moderate to good yields and MgO (400 wt%) R Ns 0 °C to r.t. high enantiomeric excesses. The cis selectivity of this transforma- (2.5 equiv) up to 85% yield tion is explained by a kinetic resolution in which only one of the 5 up to 95% ee enantiomers of 5 participates in the oxyamination. As a conse- O O quence, 2.5 equivalents of 5 are necessary for high yields.8 1-Naph 1-Naph L = N N 1-Naph 1-Naph (F) C–H Ethoxycarbonylation: O Oxaziridine 6 showed unprecedented reactivity and has been used to EtO C CO Et N CO2Et 2 2 transfer an ethoxycarbonyl group to substituted 2-phenylpyridines in H 8 moderate yields. The proposed mechanism of this reaction, cata- L O N Pd lyzed by a palladium(II) complex, involves activation of the ortho Cl N 6 C–H bond of the phenyl moiety, followed by oxidative insertion of N the metal into the N–O bond of 6, forming an intermediate palla- dium(IV) species. C–C bond cleavage of 6 followed by reductive O L elimination leads to the formation of the ethoxycarbonylated product N CO2Et N CO2Et 7 and amide 8 as the by-product. This transformation has been sub- Pd Pd O CO Et 9 N Cl 2 sequently applied to aryl urea derivatives with moderate yields. Cl CO Et L N 2 CO Et 2 Pd O N 7 N Cl CO2Et References (1) (a) Garcìa Ruano, J. L.; Alemàn, J.; Fajardo, C.; Parra, A. (4) Reddy, D. S.; Shibata, N.; Nagai, J.; Nakamura, S.; Toru, T. Org. Lett. 2005, 7, 5493. (b) Singhal, S.; Jain, S. L.; Prasad, Angew. Chem. Int. Ed. 2009, 48, 803. This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. V. V. D. N.; Sain, B. Eur. J. Org. Chem. 2007, 2051. (5) Videtta, V.; Perrone, S.; Rosato, F.; Alifano, P.; Tredici, S. (c) Bitencourt, T. B.; da Graca Nascimento, M. Green Chem. M.; Troisi, L. Synlett 2010, 2781. 2009, 11, 209. (6) Shao, P.-L.; Chen, X.-Y.; Ye, S. Angew. Chem. Int. Ed. (2) (a) Perrone, S.; Rosato, F.; Salomone, A.; Troisi, L. 2010, 49, 8412. Tetrahedron 2013, 3878. (b) Kammoun, M.; Salem, R. B.; (7) Motiwala, H. F.; Gülgeze, B.; Manyem, S.; Aubé, J. J. Org. Damack, M. Synth. Commun. 2012, 2, 2181. (c) Ghoraf, M.; Chem. 2012, 77, 7005. Vidal, J. Tetrahedron Lett. 2008, 49, 7383. (d) Armstrong, (8) Williamson, K. S.; Yoon, T. P. J. Am. Chem. Soc. 2012, 134, A.; Jones, L. H.; Knight, J. D.; Kelsey, R. D. Org. Lett. 2005, 12370 . 7, 713. (e) Kiss, E.; Markò, I. E.; Guillaume, M. Tetrahedron (9) Peng, X.; Zhu, Y.; Ramirez, T. A.; Zhao, B.; Shi, Y. Org. 2011, 67, 9173. Lett. 2011, 13, 5244. (3) Allen, C. P.; Benkovics, T.; Turek, A. K.; Yoon, T. P. J. Am. Chem. Soc. 2009, 131, 12560. Synlett 2013, 24, 2773–2774 © Georg Thieme Verlag Stuttgart · New York.