Aziridines: Overview and Recent Advancements - The Stoltz Group

Aziridines- Overview and Recent Advancements -Jan StreuffStoltzgroup - Literature Seminar01-26-2009, 8pm147 Noyes

Some Properties of AziridinePhysical Properties:HNbp = 57°CpKa (of conjug. acid) = 7.98possibly carcinogenicabsorbed through skinpotential mutagen: interacts with DNA nucleobasesStrain energy:HNOSexperimental :(calculated) :26.7 kcal/mol(26.2 kcal/mol)27.5 kcal/mol(27.3 kcal/mol)26.3 kcal/mol(24.6 kcal/mol)-(18.9 kcal/mol)J. B. Sweeney, Chem. Soc. Rev. 2002, 31, 247.R. D. Bach, O. Dmitrenko, J. Org. Chem. 2002, 67, 3884.

Inversion BarrierNHHNHHΔG = 26.8 kcal/mol(diastereomers isolable at 25°C)HΔG = 16.7 kcal/mol(inversion at 25°C)ClN NClHOMeONClONHMeno inversion at 50°CJ. B. Sweeney, Chem. Soc. Rev. 2002, 31, 247.

DNA Interaction of AziridinesOONH 2OR 1OR 2OR 1OR 2NNR 3 N N CH 3OOMitomycin AMitomycin BMitomycin CPorfiromycinR 1 = OMe, R 2 = Me, R 3 = HR 1 = OMe, R 2 = H, R 3 = MeR 1 = NH 2 , R 2 = Me, R 3 = HR 1 = NH 2 , R 2 = Me, R 3 = MeMitomycin GMitomycin HMitomycin KR 1 = NH 2 , R 2 = MeR 1 = OMe, R 2 = HR 1 = OMe, R 2 = MeR 1OR 2NOC(O)NH 2OR 3O N R 4FR-900482FR-66979FR-70496FK-973FK-317R 1 = CHO, R 2 = R 3 = R 4 = HR 1 = CH 2 OH, R 2 = R 3 = R 4 = HR 1 = CHO, R 2 = Me, R 3 = H, R 4 = AcR 1 = CHO, R 2 = R 3 = R 4 = AcR 1 = CHO, R 2 = Me, R 3 = AcOJ. B. Sweeney, Chem. Soc. Rev. 2002, 31, 247.

DNA Interaction of AziridinesOONH 2R 1OR 2OR 1OOHN+ 2e , + 2H− HOR 2NOHON R 3NH 2N R 3R 1OHORNOOHNNH 2HNNHR 3NON ONOO P OOORDNAR 1HOO NH 2OHN N R 3ORJ. B. Sweeney, Chem. Soc. Rev. 2002, 31, 247.R 1HOORNOONHNH 2R3 DNA

Other Natural Products Containing AziridinesMiraziridineHOONHONHOHNOHONHOHNNHNHNH 2CO 2 HAzinomycin AHOMeOMeOOOMeOHOH OH OOOOHHHHOOOOHNHONRONHONHOONHH 2 NFicellomycinHNH 2 NHOOOOH OH H OONHClCO 2 HNHNOOHAzicemicin A: R = HAzicemicin B: R = MeMaduropeptinMeO

Classic Aziridine SynthesesWenker's Synthesis (1935):HONH 2 H 2 SO 4250°C− H 2 OOSO2ONH 31) NaOH, Δ2) KOH3) Na, ΔHN610 g71%27%H. Wenker, J. Am. Chem. Soc. 1935, 57, 2328.Hoch-Campbell Synthesis (1934):PhN OHPhMgBr− C 6 H 6PhN OMgBrPhMgBrBrMgPhN OMgBrPhHH 2 O− 2 MgBrOHPhHNPhJ. Hoch, Compt. Rend. 1934, 198, 1865K. N. Campbell, B. K. Campbell, J. F. McKenna, E. P. Chaput, J.Org. Chem. 1943, 8, 103.

Aziridine Synthesis - OverviewX N R2 X N R2ML nX N R2R 1R 1 BrR 1 YXR 1NR 1 R 2 PhI=NXH 2 NXR 2Ti(IV)BrR 1 R 2H 2 NXR 4 PXSOCl 2 ,R 1 SOCl 2 , [O]RSO 2 ClR 1OHMN 3 NaOHNHXHOPPh 3 HOR 2ONHXR 2R 1 R 2 R 1I. D. G. Watson, L. Yu, A. K. Yudin, Acc. Chem. Res. 2006, 39, 194.T. Ibuka, Chem. Soc. Rev. 1998, 27, 145.O

A Brief Introduction to NitrenesTriplet nitrene:X N Singlet nitrene: X NEnergyLUMOEnergyp LUMOsp 2 HOMOsp HOMOnon bondingnon bondingslightly higher energystabilized by electrondonating substituentsCommon nitrene precursors:RN 3hνor Δ−N 2RNH 2 N X ROxidantN X SOR2 RX = CO, SO 2PhI NW. Schoeller, A. B. Rozhenko, Eur. J. Org. Chem. 2001, 845.W. Lwowski in Nitrenes (Ed.: W. Lwowski), Interscience, New York, 1970, pp. 1-11.

Selected Examples for the Synthesis of Aziridines from AlkenesXXNNXNR 1HH R 2R 1HH R 2R 1HH R 2XNXXNXR 1 NR 2R 1R 2R 1 R 2R 1NR 2Singlet Nitrene(stereoselective)Triplet Nitrene(not stereoselective)J. B. Sweeney, Chem. Soc. Rev. 2002, 31, 247.

Copper Catalyzed AziridinationsMeMeOOPhCO 2 RPhNN(6 mol%)PhCuOTf (5 mol%)PhI=NTs (2.0 equiv)C 6 H 6 , 21°CPhTsNCO 2 RR = MeR = Ph63% i.y., 94% ee64% i.y., 97%eeD. A. Evans, M. M. Faul, M. T. Bilodeau, B. A. Anderson, D. M. Barnes, J. Am. Chem. Soc. 1993, 115, 5328.D. A. Evans, M. M. Faul, M. T. Bilodeau, J. Am. Chem. Soc. 1994, 116, 2742.NCOClNNCl Cl(11 mol%)CuOTf (10 mol%)PhI=NTs (1.5 equiv)CH 2 Cl 2 , -78°CClNCONTs75% i.y., >98% eeZ. Li, K. R. Conser, E. N. Jacobsen, J. Am. Chem. Soc. 1993, 115, 5326.Z. Li, R. W. Quan, E. N. Jacobsen, J. Am. Chem. Soc. 1995, 117, 5889.Via copper nitrene species:L*CuNTs OTfDrawbacks: Limited substrate scopeOften an excess of the alkene required

Copper Catalyzed Aziridination - Catalytic CycleL*Cu PF 6PhI NTsR 1 R 2 R 3NTsR 1PhIR 2 R 3 L*Cu NTsPF 6Z. Li, R. W. Quan, E. N. Jacobsen, J. Am. Chem. Soc. 1995, 117, 5889.

Aziridinations with Ruthenium and RhodiumPhCatalyst (1 mol%)N 3(1.0 equiv) TMS (1.0 equiv)0°C, 12hPhCatalyst (0.1 mol%)(1.0 equiv) NsN 3 (1.0 equiv)room temp., 36hSESNPh99% i.y., 92%eeNsNPh70% i.y., 81% eeCatalyst:NOCO NRuAr ArOAr = 3,5-Cl 2 -4-(CH 3 ) 3 SiC 6 H 2H. Kawabata, K. Omura, T. Katsuki, Tetrahedron Lett. 2006, 47, 1571.NsCatalyst:PhR(20 equiv.)Catalyst (2 mol%)PhI=NNs (1.0 equiv)CH 2 Cl 2 , room temp.1.0 − 1.5 hPhNRO OO PO Rh 2R = H:R = Me:74% i.y., 55% ee80% i.y., 73% ee4P. Müller, C. Baud, Y. Jacquier, Can. J. Chem. 1998, 76, 738.M. C. Pirrung, J. Zhang, Tetrahedron Lett. 1992, 33, 5987.P. Müller, C. Fruit, Chem. Rev. 2003, 103, 2905.

Iron Catalyzed AziridinationOTMSR 1 R 2(2 equiv)R 1 = aryl, alkylR 2 = H, alkylFe(OTf) 2 (2.5 mol%)PhI=NTs (1.0 equiv)TsMS 4Å, CH 3 CNTMSOroom temp., 1h R 1 R 2NOR 1 R 2HN46-72% i.y.TsFe(OTf) 2 (5 mol%)Ligand (30 mol%)PhI=NTs (1.0 equiv)TsNLigand:ONO(20 equiv)MS 4Å ,CH 3 CNroom temp., 1h72% i.y., 40% eeNNM. Nakanishi, A.-F. Salit, C. Bolm, Adv. Synth. Catal. 2008, 350, 1835.

Main Group Element Catalyzed AziridinationR 1 R 2 PTAB (10 mol%)Chloramine-T (1.1 equiv)orCH 3 CN, 25°C12hR 1 (30-95% i.y.)R 2R 1 , R 2 = H, alkyl, aryl, CH 2 OHTsNR 1 R 2orTsNR 1 R 2PTAB:PhBrNBrBrPhenyltrimethylammoniumtribromideTsNNTsNTsTsNOH93% 51% 76%TsTsNNPh868% 54%TsN73%OH94%HO30%TsNJ. U. Jeong, B. Tao, I. Sagasser, H. Henniges, K. B. Sharpless, J. Am. Chem. Soc. 1998, 120, 6844.J. U. Jeong, K. B. Sharpless, U.S. Patent number 5,929,252, 1999.

Main Group Element Catalyzed AziridinationPhMe"Br ": Br-X (X = Cl, TsNCl, Br, etc...)Br"Br "PhMeHPhNTsBrHMePhHNHMe+ BrHPhClNBrHMeTsTsN ClTsJ. U. Jeong, B. Tao, I. Sagasser, H. Henniges, K. B. Sharpless, J. Am. Chem. Soc. 1998, 120, 6844.

Main Group Element Catalyzed AziridinationOHPTAB (10 mol%)Chloramine-T (1.1 equiv)TsN(63%)OH(E/Z mix)OHPTAB (10 mol%)Chloramine-T (1.1 equiv)(64%)TsNOHJ. U. Jeong, B. Tao, I. Sagasser, H. Henniges, K. B. Sharpless, J. Am. Chem. Soc. 1998, 120, 6844.J. U. Jeong, K. B. Sharpless, U.S. Patent number 5,929,252, 1999.AcOAcOOAcOChloramine-T (2.3 equiv)I 2 (15 mol%)CH 3 CN, 0°C14hAcOAcOOAcONAcOAcOOAcONHTsNHTsTs69%V. Kumar, N. G. Ramesh, Chem. Commun. 2006, 4952.

With Pb(OAc) 4 as oxidant:ON NH 2 +OAziridination with HydrazinesRPb(OAc) 4-20°CPhthNHR+100 : 0PhthN highly diastereoselective(singlet state nitrene)RH(R = Ph, CO 2 Me)R. S. Atkinson, M. J. Grimshire, B. J. Kelly, Tetrahedron 1989, 45, 2875.R. S. Atkinson, D. W. Jones, B. J. Kelly, J. Chem. Soc., Perkin Trans. 1 1991, 1344.Electrochemically (platinum electrodes):OONNH 2+ R 1 R 2T. Siu, A. K. Yudin, J. Am. Chem. Soc. 2002, 124, 530.+ 1.8V (vs. Ag)HNEt 3 OAcroom temperaturePhthNR 1 R 2(R 1 , R 2 = alkyl, aryl, allyl, EWG)With PhI(OAc) 2 as oxidant:OPhthNONH 2+ R 1 PhI(OAc) 2 (2.0 equiv)R 2 room temperatureNR 1 R 2(R 1 , R 2 = alkyl, aryl, allyl, EWG)L. B. Krasnova, R. M. Hili, O. V. Chernoloz, A. K. Yudin, ARKIVOC 2005, 4, 26.

Aziridination with HydrazinesOPb(OAc) 4NO or+1.8 V (vs Ag)NHHNEt 3 OAc2OONNHO− PhIOPhINNHOPhI(OAc) 2− HOAc ONNH 2OProblematic substrates:MeOBrnOMeO 2 COOCO 2 MeOOAziridinating reagentR 1 R 2OH ONNOO R 1 R 2OAcONONR 1 R 2Observed sidereaction (electrochemically and with Pb(OAc) 4 ):O[O]H2 PhthN NHPhthN N[O]PhthN N2NH NPhth N NPhth[O]− N 22NHL. Hoesch, A. S. Dreiding, Chimia, 1969, 23, 405.I. D. G. Watson, L. Yu, A. K. Yudin, Acc. Chem. Res. 2006, 39, 194.O

Aziridine Transformations - Ring OpeningDiaminesβ-AminosulfidesR 1 NHR 4R 2 NHR 3R 1 NHR 3R 2 SR 4R 1 OR 4 β-AminoalcoholsR 2 NHR 3COR 4R 1 NHR 3R 2 COR 4R 1 NHR 3R 2 R 2NR 1 R 1Dimerization productsNR 3 R 2PolymersR 3NN R27 kcal / molAminesR 1 CH 2 R 4NHR 3R 2OR 1 P(OR) 2AminophosphonatesR 2 NHR 3I. D. G. Watson, L. Yu, A. K. Yudin, Acc. Chem. Res. 2006, 39, 194.T. Ibuka, Chem. Soc. Rev. 1998, 27, 145.

Concepts for the Activation of AziridinesActivation by protonation:N + Nuc HHH HNuc NHNNNuc2(basic)NucActivation by alkylation:ClCO 2 EtHN1)2) LDANHCO 2 EtCO 2 EtN CO 2 Et NClIsolable aziridinium compounds:Ph 3 PPhPhPh OCBr 4N OH PPh 3 N − O PPh 3tBuO 2 CtBuO 2 CtBuOCO 2 tBu2 CCO 2 tBuH. A. Song, M. Dadwal, Y. Lee, E. Mick, H.-S. Chong, Angew. Chem. Int. Ed. 2009, early view.NBrCO 2 tBu

Activation with substituents:OORSR 1NORSR 1NR 1 OORConcepts for the Activation of AziridinesPOR 1NR 1ORPR 1NOROR 1NORR 1NO R 1NRweak amide resonance(increased ring strain)Activation with Lewis acids:LAOR 1NLAOR 1X LANLAOXR 1NRR(R 1 = H, alkyl)RR(indirect interaction)Kinetic activation:Thermodynamic activation:R 1ONR(polarization)ORR 1NNucRNucNORR 1Nuc(stabilization)NOR 1

Enantioselective Opening of AziridinesLiO N SO 2 -t-BunBuLi (3.0 equiv)(−)-Sparteine (3.0 equiv)Et 2 O-78°C to 0°CONLiSO 2 -t-BuHOSO 2 -t-BuNH30% i.y., 25% eeD. M. Hodgson, B. Stefane, T. J. Miles, J. Witherington, Chem. Commun. 2004, 2234.O 2 NNO 2Catalyst (10 mol%)TMSN 3 (1.05 equiv)ArHN N 3Catalyst:PhNMS 4Å, acetone-30°C, 48h95% i.y., 94% eeNOCrON 3Ph MeZ. Li, M. Fernández, E. N. Jacobsen, Org. Lett. 1999, 1, 1611.Catalyst:PhNTsCatalyst (30 mol%)MeMgBr (10 equiv)THF, 0°C1.5 hNHTsMe52% i.y., 91% eeOPhONO CuOCuNOOP. Müller, P. Nury, Org. Lett. 1999, 1, 439.

Catalytic Enantioselective Opening of AziridinesHNRCNR = 4-Nitrobenzoyl85% i.y., 82% eeGd(O i Pr) 3 (10 mol%)Ligand (20 mol%)TFA (5 mol%)2,6-Dimethylphenol (1 equiv)TMSCN (3 equiv)CH 3 CH 2 CNroom temp., 95hNRY(O i Pr) 3 (2 mol%)A (4 mol%)TMSN 3 (1.5 equiv)CH 3 CH 2 CNroom temp., 48hHNRN 3R = 3,5-Dinitrobenzoyl96% i.y., 91% eeLigand:PhPhPOHOOOFONHAcHOFEtO 2 CNH 2 •H 3 PO 4TamifluY. Fukuta, T. Mita, N. Fukuda, M. Kanai, M. Shibasaki, J. Am. Chem. Soc. 2006, 128, 6312.T. Mita, I. Fujimori, R. Wada, J. Wen, M. Kanai, M. Shibasaki, J. Am. Chem. Soc. 2005, 127, 11252.

Enantioselective Opening of AziridinesOTMSCN (1.0 equiv)Conditions25°COSiMe 3CN2 mol% Catalyst, CH 2 Cl 2 :0.01 mol% Catalyst, neat :100% conv., 77% ee (2h)100% conv., 56%ee (4h)RRCatalyst (dimer):NNOYONORNO 2RNH(CO)ArTMSN 3 (3.0 equiv)Catalyst (10 mol%)TMSCN (3.0 equiv)Catalyst (10 mol%)NH(CO)ArN 399% i.y., 97% eeDCE, 25°C72hNODCE, 25°C72hCN87% i.y., 94% eeB. Saha, M.-H. Lin, T. V. RajanBabu, J. Org. Chem. 2007, 72, 8648.B. Wu, J. C. Gallucci, J. R. Parquette, T. V. RajanBabu, Angew. Chem. Int. Ed. 2009, early view.

Asymmetric Opening of Aziridines with chiral AcidsRRNOCF 3Acid (10 mol%)TMSN 3 (1.0 equiv)DCE, room temp21-91hHR N ArOR N 3Acid:PhPhO OO POHF 3 C(1.5 equiv)12 examples49-97% yield (70-95% ee)E. B. Rowland, G. B. Rowland, E. Rivera-Otero, J. C. Antilla, J. Am. Chem. Soc. 2007, 129, 12084.PhPhClR 1NR 2R 3 -OH (4.0 equiv)Acid (15 mol%)Ag 2 CO 3 (0.6 equiv)4Å MS, PhCH 3 , 50°C24-36hPhNPh(meso)R 1R 2RROR 3R 1NR 211 examples56-95% yield (90-99% ee)Acid:i Pri Pri Pri PrO OO P i OHPri PrG. L. Hamilton, T. kanai, F. D. Toste, J. Am. Chem. Soc. 2008, 130, 14984.

N-Functionalization of AziridinesReactivity of Amines:OR 1 H R 3NR 2HR 1 + H 2 ONOHR 3 − H 2 OR 2R 1 N R 3 NaCNBH 3 R 1 N R 3R 2R 2Reactivity of Aziridines:R 1R 1NHR 3 OHR 1OHNR 1 R 3R 1NR 1 R 3isolable(highly strained)I. D. G. Watson, L. Yu, A. K. Yudin, Acc. Chem. Res. 2006, 39, 194.

Palladium Catalyzed Allylation of AziridinesNH+PhOAcPhPd ClCl Pd(1 mol%)(R)-BINAP (4 mol%)THF, room temp.NPhPh97% i.y., 97% eeResults obtained with PPh 3 as ligand (ratio = linear : branched) :N45 %PhNNNPhO80% (12:88)99% (92:8) 79%MeO 2 CCO 2 MeNNNPh89% i.y. (0:100)64%84%I. D. G. Watson, S. A. Styler, A. K. Yudin, J. Am. Chem. Soc. 2004, 126, 5086.

Palladium Catalyzed Allylation of AziridinesN BnBnNH 2PdLNHNthermodynamic productL = (rac)-BINAPkinetic productPossible explanations:NHN• pKa difference• product inhibitionNPdthermodynamic productMonitoring the reaction over time:NHOAcPd 0 / BINAPNkinetic productPd 0 / BINAPre-insertionNthermodynamic productI. D. G. Watson, S. A. Styler, A. K. Yudin, J. Am. Chem. Soc. 2004, 126, 5086.I. D. G. Watson, A. K. Yudin, J. Am. Chem. Soc. 2005, 127, 17516.

Palladium Catalyzed Allylic AminationPhN[(allyl)PdCl] 2 (1 mol%)P(OEt) 3 (4 mol%)no baseTHF, room temp.Ph NH 2+OAc[(allyl)PdCl] 2 (1 mol%)P(OEt) 3 (4 mol%)DBU (1 equiv)THF, room temp.Ph NHno isomerization !XHN RHthermodynamic product(linear)RNH 2− Pd 0 L 2LPdRR XLLPdXLPdL 2RN− RNH 2H H− Pd 0 L 2RNPd 0 L 2RNH 2R RHRHRXkinetic product(branched)I. Dubovyk, I. D. G. Watson, A. K. Yudin, J. Am. Chem. Soc. 2007, 129, 14172.

Cycloamination Reactions of AziridinesMeOOOHOOOOHNHOHONNHOH 2 NHNH 2 NONHCO 2 HNHAzinomycin AFicellomycinConcept: CycloaminationBrHN NBS KOHNNG. Chen, M. Sasaki, X. Li, A. K. Yudin, J. Org. Chem. 2006, 71, 6067I. D. G. Watson, L. Yu, A. K. Yudin, Acc. Chem. Res. 2006, 39, 194.

Cycloamination Reactions of AziridinesNHR 1 R 2 DME/H 2 O, 0°C2hNBS (1.2 equiv)orNBS (1.1 equiv)CH 2 Cl 2 , 40°C24hBrR 1HR 2N HR 1 = H, alkylorBrR 1HNR 1 = arylR 2HHCOPhHHHCOPhNHNCOPhBrNHBrBrPh98% (d.r.: 74:26)68% (d.r.: > 99:1)67% (d.r.: 81:19)HCOPhHCOPhHNBrH51% (d.r.: 67:33)HHOH 2 CNBrH51% (d.r.: 67:33)G. Chen, M. Sasaki, X. Li, A. K. Yudin, J. Org. Chem. 2006, 71, 6067

Cycloamination Reactions Transition StateNHCOPhHCOPhN HBr98% (d.r.: 74:26)NHCOPhHHN COPhBr68% (d.r.: > 99:1)BrHHNHCOPhBrHHN HCOPh1,3-interactionRHCOPhN HBrR = H, MeKOH1% MeOH in THFroom temp., 30 minRNH99%COPhHG. Chen, M. Sasaki, X. Li, A. K. Yudin, J. Org. Chem. 2006, 71, 6067

Cycloamination Reactions and Follow-Up ChemistryRHNHHPhDIBAL-HRNHPhRNHOPhNH 2 NH 2KOHPd, H 2RNHOPh1) NBS2) KOHR = H, Me1) NBS2) KOHR = ArBrRHNHHNHOPhOPhNuH1) DebrominationRNHNuOPh2) NuH, Acid Ar N PhHHOArNuNH 2 NH 2KOH"Aziridine relay"HNPhOC HI. D. G. Watson, L. Yu, A. K. Yudin, Acc. Chem. Res. 2006, 39, 194.Ph

Cycloamination Reactions and Follow-Up ChemistryRHNHHPhDIBAL-HRNHPhRNHOPhNH 2 NH 2KOHPd, H 2RNHOPh1) NBS2) KOHR = H, Me1) NBS2) KOHR = ArBrRHNHHNHOPhOPhNuH1) DebrominationRNHNuOPh2) NuH, Acid Ar N PhHHOHNNHArNH 2 NH 2KOH"Aziridine relay"NuBrNHPhHArNPhOC HI. D. G. Watson, L. Yu, A. K. Yudin, Acc. Chem. Res. 2006, 39, 194.Ph

Aziridinoaldehydes - Kinetic AmphotersNHOOMeDIBAL-H-78°C, TolueneNHOHH +NOHNHONH 3OHNOHNOHHNHOHorthogonal reactivitythermodynamicamphoter(zwitterionic)76% i.y.• stable to racemization• water-solublekineticamphoterR. Hili, A. K. Yudin, J. Am. Chem. Soc. 2006, 128, 14772.A. K. Yudin, R. Hili, Chem. Eur. J. 2007, 13, 6538.

Aziridinoaldehydes - Kinetic AmphotersR 1HHNHOEtODIBAL-H (2 equiv)-78°C, TolueneHNR 1HOHOHHN HR 1OHOHOHHN N HOPhHPhHHN NPhPh83% OH81%OHHN N HHHSHNSTBDMSO92%R. Hili, A. K. Yudin, J. Am. Chem. Soc. 2006, 128, 14772.OHOHHN NH76%OHOHN HHOTBDMSH94%

Aziridinoaldehydes - ReactivityOHHNHNaBH 4HPhOHNHHPhOHHN HPhOHNHHPhHAnilineNaCNBH 3HN99%HNHPhPh H99%R. Hili, A. K. Yudin, J. Am. Chem. Soc. 2006, 128, 14772.

Aziridinoaldehydes - Polyheterocycle SynthesisHO HHN(Dimer)HPhNHTFE0°C, 3hNHBn(1 equiv)N H HHPhNHBn(syn)HNΔor cat. H 2 ON H HHPhNHBnH(anti)N0°C:−20°C:97%, (syn/anti = 8:1)94%, (syn/anti = 20:1)BnBnBnN H PhN H HN H HHOTBDMSNHNNH NHNH N HH81%, (syn/anti = 2:1) 74%, (syn/anti = 1.5:1) 94%, (syn/anti = 3:1)R. Hili, A. K. Yudin, J. Am. Chem. Soc. 2006, 128, 14772.

Polyheterocycle Formation - MechanismNHNHBnHNPhH HOHNHHPhNHHNPhNNHPhHHHPhNHBnN H HHPhNHHNN H HHPhNHBnR. Hili, A. K. Yudin, J. Am. Chem. Soc. 2006, 128, 14772.A. K. Yudin, R. Hili, Chem. Eur. J. 2007, 13, 6538.HNPhSH5 mol% Zn(OTf) 2CH 2 Cl 2 , 23°C, 1hNNHBnHHNHPhSPh

Conclusion• The direct aziridination of olefins is more difficult than the corresponding epoxidation• A general solution towards an enantioselective ring-opening of aziridines does not exist• Partial solutions have been discovered over the past 10 years but they are very specific• Aziridines react different than amines in N-allylation reactions (under the same conditions)• Cycloamination of aziridines leads to building blocks for heterocycle chemistry and natural products• Aziridinoaldehydes are kinetic amphoters with unique reactivityLiterature:Aziridines and Epoxides in Organic Synthesis (Ed.: A. K. Yudin),Wiley-VCH, Weinheim, 2006.A. K. Yudin, R. Hili, Chem. Eur. J. 2007, 13, 6538.I. D. G. Watson, L. Yu, A. K. Yudin, Acc. Chem. Res. 2006, 39, 194.M. Pineschi, Eur. J. Org. Chem. 2006, 4979.A. Padwa, S. S. Murphree, ARKIVOC 2006, 3, 6.J. B. Sweeney, Chem. Soc. Rev. 2002, 31, 247.H. M. I. Osborn, J. Sweeney, Tetrahedron: Asymmetry 1997, 8, 1693.D. Tanner, Angew. Chem., Int. Ed. Engl. 1994, 33, 599.