(organic chemists)

Literature meeting Carl TrudelFebruary 7th 2011Oxaziridines : What Can You Do With A Strained Three-Membered Heterocycle*

Some GeneralitiesFirst discovered by William D. Emmons in 1956.Worked for Rohm and Haas Company's (Dow Chemical Company) HWE (least imaginative of his work!)Died in 2001

Discovery followed by H. Krimm and... ... L. Horner!

Emmons, W. D. J. Am. Chem. Soc. 1956, 78, 6208-6209. Horner, L.; Jrgens, E. Chem. Ber. 1957, 90, 2184-2189.*

Davis OxaziridinesDavis, F. A. et al. J. Am. Chem. Soc. 1988, 110, 8477-8482.Davis, F. A.; Sheppard, A. C. J. Org. Chem. 1987, 52, 954-955. Evans, D. A. et al. J. Am. Chem. Soc. 1985, 107, 4346-4348.

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The ProgramSome generalities

Oxaziridines preparation

Their properties

Their reactivityPhotoisomerisationO-transfer agentsN-transfer agentsDipolar cycloaddition agent*

Oxaziridines Preparation : Imines Oxidation Emmons, W. D. J. Am. Chem. Soc. 1956, 78, 6208-6209. Horner, L.; Jrgens, E. Chem. Ber. 1957, 90, 2184-2189.Widmer, J.; Keller-Schierlein, W. Helv. Chim. Acta 1974, 57, 657-664.Aube, J. et al. J. Am. Chem. Soc. 1995, 117, 5169-5178.*

Stereochemical considerationsSyn-directing OHAnti to EWGWang, Y.; Chackalamannil, S.; Aube, J. J. Org. Chem. 2000, 65, 5120-5126.*

Proposed MechanismImine geometry has little effect (stereoselectivity vs specificity).Faster for electron poor imines and electron rich peracids.Accelerated by protic solvents.Electrophilic oxydant (DMDO) generates significant amount of nitrone.Aube, J. et al. J. Org. Chem. 2000, 65, 5120-5126. Belzecki, C.; Mostowicz, D. J.Org. Chem.1975, 40, 3878-3880. Ogata, Y.; Sawaki, Y. J. Am. Chem. Soc. 1973, 95, 4687-4692. Nose, .; Kova, F. Int. J. Chem. Kinet. 2007, 39, 492-497.*

Other Schiff Base OxydationJain, S. L.; Singhal, S.; Sain, B. J. Organomet. Chem. 2007, 692, 2930-2935.Davis, F. A.; Chattopadhyay, S.; Towson, J. C.; Lal, S.; Reddy, T. J. Org. Chem. 1988, 53, 2087-2089.Kraem, J.; Ben Othman, R.; Ben Hassine, B. C. R. Chim., 2004, 7, 1119-1126.*

NH Oxaziridines : Ketones AminationAnreae, S.; Schmitz, E. Synthesis 1991, 327-341. Schulz, M.; Becker, D.; Rieche, A. ACIE 1965, 4, 525-526.*

Photololysis of Nitrones

This mechanism may be involved in the photochemical epimerization of oxaziridines.Ning, R. Y.; Field, G. F.; Sternbach, L. H. J. Heterocycl. Chem. 1970, 7, 475-478. Boyd, D. R. et al. J. Chem. Soc., Chem. Commun. 1976, 162-163.*

Some ConsiderationsPhotochemical epimerization

Thermal nitrogen inversion is unfavoredRing strain increases in TSInductive effect of adjacent O

Boyd, D. R. J. Chem. Soc., Chem. Commun. 1992, 1078-1079. Boyd, D. R. J. Chem. Soc., Perkin Trans. 2 1973, 1575-1577.

Boyd, D. R. et al. J. Chem. Soc., Chem. Commun. 1976, 162-163.*

The ProgramSome generalities

Oxaziridines preparation

Their properties

Their reactivityPhotoisomerisationO-transfer agentsN-transfer agentsDipolar cycloaddition agent*

Photo- Oxaziridine to Amide RearrangementBiradical mechanismConcerted alkyl migration

C-C bond anti to the hydrogen lone pairMalrieu, J. P. et al. J. Am. Chem. Soc. 1979, 101, 318-322. Lattes, A. et al. J. Am. Chem. Soc. 1982, 104, 3929-3934.*

Oxaziridines to AmidesPhotochemical process

Apparent less stable radical leads to the product

Nitrones also work altough with lower yieldsMore strained product is obtained

Lattes, A. et al. J. Am. Chem. Soc. 1982, 104, 3929-3934. Girard, J.-P. et al. Org. Lett. 2001, 3, 3067-3070. Aube, J. Chem. Soc. Rev. 1997, 26, 269.*

Oxaziridines to AmidesTransition metal catalysed processOpposed stereoselectivityStereospecificSuda, K.; Sashima, M.; Izutsu, M.; Hino, F. J. Chem. Soc., Chem. Commun. 1994, 949-950.*

Oxaziridines to AmideTransition metal catalysed process

Stabilised intermediateSubstituent syn to the lone pair migrates

Towards an atom economic amid synthesis?Suda, K. et al. J. Chem. Soc., Chem. Commun. 1994, 949-950. Crabtree, R. H. et al. Green Chem. 2007, 9, 976-979.

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The ProgramSome generalities

Oxaziridines preparation

Their properties

Their reactivityPhotoisomerisationO-transfer agentsN-transfer agentsDipolar cycloaddition agent*

O Transfer AgentsCan act as O or N transfer agentsN substituent tunes the reactivitySteric and electronic effectsElectron poor imine derivatives react fasterNucleophiles may react in a SN2 fashion (N-O bond)Or via a concerted asynchronous TS

Epoxidations occurs in a spiro transition stateDavis, F. A. et al. J.Org. Chem. 1986, 51, 4240-4245. Houk, K. N. et al. J. Am. Chem. Soc. 1997, 119, 10147-10152.*

Asymetric Enolate Oxidation SN2-typem attackRacemic oxaziridine

Evans, D. A. et al. J. Am. Chem. Soc. 1985, 107, 4346-4348.*

Dynamic Kinetic Asymetric HydroxylationReddy, D. S.; Shibata, N.; Nagai, J.; Nakamura, S.; Toru, T. Angew. Chem. Int. Ed. 2009, 48, 803-806.*

O Transfer to Heteroatom : Sulfur OxidationClerici, F. et al. Tetrahedron: Asymmetry 2009, 20, 2247-2256. Guillen, F. et al. Tetrahedron: Asymmetry 2007, 18, 2959-2964.*

Intramolecular EpoxidationIntramolecular process proven by competitive experiment with 13C and 18O labeled oxaziridineAnderson, D. R.; Woods, K. W.; Beak, P. Org. Lett. 1999, 1, 1415-1417.*

Intramolecular EpoxidationElectron rich alkene

Regiocontrol via a six-membered ring transition stateArmstrong, A.; Draffan, A. G. J. Chem. Soc., Perkin Trans. 1 2001, 2861-2873.*

Catalytic EpoxidationPhosphonio imine can be converted in situ in oxaziridine oxidant.

Reaction takes 3 to 45 hoursConcerted mechanismElectron rich alkene reacts firstCyclohexene derivatives showed increased reactivity over linear alkenePrieur, D.; El Kazzi, A. e.; Kato, T.; Gornitzka, H.; Baceiredo, A. Org. Lett. 2008, 10, 2291-2294.*

Oxaziridinium SaltFaster than m-CPBA C=O directed (vs O-H)

Hanquet, G. et al.Tetrahedron Lett. 1993, 34, 7271-7274. Lusinchi, X.; Hanquet, G. Tetrahedron 1997, 53, 13727-13738. Boh, L.; Lusinchi, M.; Lusinchi, X. Tetrahedron 1999, 55, 141-154.*

Oxaziridinium SaltFaster than m-CPBA C=O directed (vs O-H)Stoechiometric oxaziridinium gave 42% ee.

5 mol% of iminium, oxone/NaHCO3 system at RTHanquet, G. et al.Tetrahedron Lett. 1993, 34, 7271-7274. Lusinchi, X.; Hanquet, G. Tetrahedron 1997, 53, 13727-13738. Boh, L.; Lusinchi, M.; Lusinchi, X. Tetrahedron 1999, 55, 141-154.*

Improving the Asymmetric EpoxidationPage, P. C. B. et al. J. Org. Chem. 1998, 63, 2774-2777. Page, P. C. B. et al. J. Org. Chem. 2001, 66, 6926-6931.*

Improving Asymmetric EpoxidationOxidation step is less selective at 0C.

Page, P. C. B. et al. J. Org. Chem. 2001, 66, 6926-6931.*

Improving the Asymmetric EpoxidationPage, P. C. B. et al. J. Org. Chem. 1998, 63, 2774-2777. Page, P. C. B. et al. J. Org. Chem. 2001, 66, 6926-6931.*

Perfluorinated OxaziridinesPerfluorinated Oxaziridines are stable up to 120CFairly strong oxidant

Oxidizes sulfides to sulfoxides or sulfones, pyridine and tertiary amines to N-Oxides, silanes to silanol and alcohol and ethers to ketonesCan perform epoxidation on unactivated or electron poor alkenes.Petrov, V. A.; Resnati, G. Chem. Rev. 1996, 96, 1809. Resnati, G. et al. J. Org. Chem. 1994, 59, 5511-5513.

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Perfluorinated Oxaziridines And capable of C-H bond activation!

Enantiospecific3 C-H > 2 C-H >> 1 C-HEquatorial > AxialOxidized alcohol and ethersResnati, G. et al. J. Org. Chem. 1994, 59, 5511-5513. Sorochinsky, A. E.et al. Tetrahedron 1997, 53, 5995-6000.*

Catalytic Hydroxylation of 3 C-H BondsBrodsky, B. H.; Du Bois, J. J. Am. Chem. Soc. 2005, 127, 15391-15393. Litvinas, N. D.; Brodsky, B. H.; DuBois, J. Angew. Chem. Int. Ed. 2009, 48, 4513-4516.*

Catalytic Hydroxylation of 3 C-H BondsBrodsky, B. H.; Du Bois, J. J. Am. Chem. Soc. 2005, 127, 15391-15393. Litvinas, N. D.; Brodsky, B. H.; DuBois, J. Angew. Chem. Int. Ed. 2009, 48, 4513-4516.*

The ProgramSome generalities

Oxaziridines preparation

Their properties

Their reactivityPhotoisomerisationO-transfer agentsN-transfer agentsDipolar cycloaddition agent*

N Transfer AgentsCan act as O or N transfer agentsN substituent tunes the reactivitySmaller alkyl groups Carbonyl derivativesR1 and/or R2 are EWG

Betaine intermediate?Vidal, J. et al. Chem. Euro. J. 1997, 3, 1691-1709.*

N-N Bond FormationBulkier aminesAminoestersAnilinesOne-pot 1,3,5-pyrazolesVidal, J. et al. Tetrahedron Lett. 1998, 39, 8845-8848. Armstrong, A. et al. Org. Lett. 2005, 7, 713-716.*

N-O Bond formationFoot, O. F.; Knight, W. Chem. Commun. 2000, 975-976.*

N-S Bond FormationCompetitive oxidation pathway

Solvant and temperature play an important role

Not a steric effectVidal, J. et al. Chem. Euro. J. 1997, 3, 1691-1709. Armstrong, A.; Cooke, R. S. Chem. Commun. 2002, 904-905.*

N-S Bond and Sigmatropic RearrangementArmstrong, A.; Cooke, R. S. Chem. Commun. 2002, 904-905. Armstrong, A. et al. J. Org. Chem. 2006, 71, 4028-4030. Armstrong, A.; Cooke, R. S.; Shanahan, S. E. Org. Biomol. Chem. 2003, 1, 3142.*

N-H Oxaziridines : C Aminating Agents

Very reactive towards nucleophilic attackGood aminating agentsAndreae, S.; Schmitz, E. Synthesis 1991, 327-341.*

C-N Bond FormationAndreae, S.; Schmitz, E. Synthesis 1991, 327-341. Bulman Page, P. C. et al. J. Org. Chem. 2002, 67, 7787-7796.

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N-Substituted Oxaziridines Issues Competitive aldol addition with enolates

Competitive diaminationArmstrong, A.; Edmonds, I. D.; Swarbrick, M. E.; Treweeke, N. R. Tetrahedron 2005, 61, 8423-8442.*

Electrophilic Amination Of DiorganozincLow reactivity of R2Zn towards ketones or aldehydesGhoraf, M.; Vidal, J. Tetrahedron Lett. 2008, 49, 7383-7385.*

Intramolecular Amination of C-H BondsTeshik P. YoonA.B., Harvard University (Evans), 1996M.S., Caltech (Carreira), 1998Ph.D., Caltech (MacMillan), 2002Postdoc, Harvard (Jacobsen), 2002-2005Assistant Professor of Chemistry, 2005present

University of Wisconsin, Madison

Total synthesis, visible light photocatalysisNew reactions of oxaziridines.

Same State as the Green Bay Packers!

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Intramolecular Amination of C-H Bonds

Various exemples, 61 87% yields

Aliphatic oxaziridines work as well.Hemiaminal can also be trapped with other reagent to afford, in one pot, ketoamine, homoallylamine, etc.Allen, C. P.; Benkovics, T.; Turek, A. K.; Yoon, T. P. J. Am. Chem. Soc. 2009, 131, 12560-12561.*

The ProgramSome generalities

Oxaziridines preparation

Their properties

Their reactivityPhotoisomerisationO-transfer agentsN-transfer agentsDipolar cycloaddition agent*

Dipolar Cycloadditions

Three cycloaddition pathway should be tuneable with appropriate reaction conditions. Michaelis, D. J.; Ischay, M. A.; Yoon, T. P. J. Am. Chem. Soc. 2008, 130, 6610-6615.*

Hydroxyamination

CuCl2/BuN4+Cl- showed enhanced reactivityN-Nosyl oxaziridines were proven more reactiveA FeIII has been developped.

Knappke, C. E. I.; JacobivonWangelin, A. ChemCatChem, 2010, 2, 1381-1383. Yoon, T. P. et al. J. Org. Chem. 2009, 74, 5545-5552. Williamson, K. S.; Yoon, T. P. J. Am. Chem. Soc., 2010, 132, 4570-4571.*

Stereoselective Hydroxyamination

Cationic or radical pathways are proposedYoon, T. P. et al. J. Org. Chem. 2009, 74, 5545-5552. Shao, P.-L.; Chen, X.-Y.; Ye, S. Angew. Chem. Int. Ed., 2010, 49, 8412-8416.*

Isoxazolidines PreparationPartridge, K. M.; Guzei, I. A.; Yoon, T. P. Angew. Chem. Int. Ed., 2010, 49, 930-934. *

Chirality Transfer to IsoxazolidinesCarbonyl imine intermediateThermally allowed, conrotatory electrocyclicEWG increase the lifetime of the intermediateStereospecific

Chirality can be transfered from N-substituent in thermal cycloadditionPartridge, K. M.; Guzei, I. A.; Yoon, T. P. Angew. Chem. Int. Ed., 2010, 49, 930-934. Troisi, L. et al. Tetrahedron: Asymmetry 2008, 19, 2246-2251.*

Formal Nitrones CycloadditionTroisi, L. et al. Synlett 2010, 18, 2781-2783. Kivrak, A.; Larock, R. C. J. Org. Chem. 2010, 75, 7381-7387.

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Summary

Oxaziridines preparation is relatively easy

Properties widely tuneable

Amide precusorHeteroatom transfer agentLimitless [3+2] Cycloadditions

Need to be investigated

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The End*