Catalyticrearrangements
astoolsinorganicsynthesis
Nuno MaulideUniversity of Vienna
Institute of Organic Chemistry
Plus Lucis FortbildungswocheFeb 25. 2015
From design to serendipitous discovery... And back
2
Overviewof researchintheMaulideGroup(2009‐2015)
Amide activation methodologies
Cyclobutene synthesis and chemistry
Nu
CO2H
H
HO O
"f lat" achiralstarting mater ial
2) Nucleophile Nu
1) h
f unctionalisedcyclobutene
Angew. Chem. 2010, 122, 5807Angew. Chem. 2011, 123, 12840
Synlett 2011, 22, 735Angew. Chem. 2012, 124, 2869Angew. Chem. 2012, 124, 7426ChemCatChem 2013, 5, 1239
Synlett 2013, 24, 1286Chem. Eur. J. 2013, 19, 6566
Angew. Chem. 2013, 125, 6434Org. Lett. 2013, 15, 2318
Angew. Chem. 2013, 125, 9845Angew. Chem. 2014, 126, 7188
Organic redox‐neutral reactions
New perspectives on the chemistry of Sulfur
3
Overviewof researchintheMaulideGroup(2009‐2015)
Amide activation methodologies
Cyclobutene synthesis and chemistry
Nu
CO2H
H
HO O
"f lat" achiralstarting mater ial
2) Nucleophile Nu
1) h
f unctionalisedcyclobutene
Angew. Chem. 2010, 122, 5807Angew. Chem. 2011, 123, 12840
Synlett 2011, 22, 735Angew. Chem. 2012, 124, 2869Angew. Chem. 2012, 124, 7426ChemCatChem 2013, 5, 1239
Synlett 2013, 24, 1286Chem. Eur. J. 2013, 19, 6566
Angew. Chem. 2013, 125, 6434Org. Lett. 2013, 15, 2318
Angew. Chem. 2013, 125, 9845Angew. Chem. 2014, 126, 7188
Organic redox‐neutral reactions
New perspectives on the chemistry of Sulfur
Fomannosin:retrosynthesisvia [2+2]cycloadditionchemistry
Ghosez, L.; Marchand‐Brynaert, J., Adv. Org. Chem. 1976, 9, Pt. 1, 421
Snider, B. B., Chem. Rev. 1988, 88, 793
Chemistryofketeniminiumsalts
Keteniminium salts are a class of heterocumulenes that are characterized by the cumulative arrangement of olefin and iminium groups.
L. Ghosez, J. Marchand‐Brynaert, in Iminium Salts in Organic Chemistry, Part 1 (Eds.: H. Böhme, H. G. Viehe), Wiley: New York, New York, 1976, pp. 421.J. C. Jochims et al., Chem. Ber. 1982, 115, 172.C. Madelaine, V. Valerio, N. Maulide, Chem. Asian J. 2011, 6, 2224.
Characteristic: high reactivity toward nucleophilic reagents
Generally unstable.Stable long‐lived keteniminium salts are only possible under special conditions and
require weakly nucleophilic counterions (BF4‐, ZnCl3‐, PF6‐)
Preparationofketeniminiumsalts
‐ by protonation of ynamines or ynamides
‐ from ‐(pseudo)haloenamines
‐ by alkylation of the corresponding ketenimines at nitrogen
F. Hallmann, Ber. Dtsch. Chem. Ges., 1876, 9, 846; L. Ghosez et al., Adv. Org. Chem. 1976, 9, Pt.1, 421.Deyrup, J. A. and Kuta, G. S. J. Org. Chem. 1978, 43, 501.J. Ficini, C. Barbara, Tetrahedron Lett. 1966, 6425; DeKorver, K. A., Li, H., Lohse, A. G., Hayashi, R., Lu, Z., Zhang, Y., Hsung, R. P. Chem. Rev. 2010, 110, 5064
TypicalreactivityofKeteniminiumSalts:2+2cycloaddition
J. Marchand‐Brynaert, L. Ghosez, J. Am. Chem. Soc. 1972, 94, 2870.B.B. Snider, Chem. Rev. 1988, 88, 793.C. Madelaine, V. Valerio, N. Maulide, Chem. Asian J. 2011, 6, 2224
BacktotheRetrosyntheticplan
Ghosez, L.; Marchand‐Brynaert, J., Adv. Org. Chem. 1976, 9, Pt. 1, 421Snider, B. B., Chem. Rev. 1988, 88, 793
Unexpectedobservation
Ghosez, L.; Marchand‐Brynaert, J., Adv. Org. Chem. 1976, 9, Pt. 1, 421Snider, B. B., Chem. Rev. 1988, 88, 793
ElectrophilicAmideActivation
With Claire Madelaine and Viviana Valerio:Angew. Chem. 2010, 122, 1628Chem. Eur. J. 2011, 17, 4742Chem. Asian J. 2011, 6, 2224
Carbonyl ‐Arylation
Reviews: (a) Bellina, F.; Rossi, R. Chem. Rev. 2010, 110, 1082. (b) Ma, D.; Cai, Q. Acc. Chem. Res. 2008, 41, 1450. (c) Culkin, D. A.; Hartwig, J. F. Acc. Chem. Res. 2003, 36, 234
Arynes: Tadross, P. M.; Gilmore, C. D.; Bugga, P.; Virgil, S. C.; Stoltz, B. M. Org. Lett. 2010, 12, 1224 Organobismuth reagents: (a) Barton, D. H. R.; Finet, J.‐P. Pure Appl. Chem. 1987, 59, 937. (b) Elliott, G.; Konopelski, J. P. Tetrahedron 2001, 57, 5683. Organolead reagents: (a) Orito, K.; Sasaki, T.; Suginome, H. J. Org. Chem. 1995, 60, 6208. (b) Xia, J.; Brown, L. E.; Konopelski, J. P. J. Org. Chem. 2007, 72, 6885.
Hypervalent iodine: (a) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299. (b) Olofsson, B.; Merritt, E. A. Angew. Chem. Int. Ed. 2009, 48, 9052.
Xu, Q.-L.; Gao, H.; Yousufuddin, M.;Ess, D. H.; Kurti, L. J. Am. Chem. Soc. 2013, 135, 14048
Initialreactiondesign
Chem. Eur. J. 2011, 17, 4742With Claire Madelaine and Viviana Valerio: Angew. Chem. Int. Ed. 2010, 49, 1583
35-90% yieldsLimited scope
Unexpectedobservation
Xueliang Huang
Ylidetransferreactions
With Xueliang Huang : Angew. Chem. Int. Ed. 2010, 49, 8979;Angew. Chem. 2010, 122, 9163.
Ylidetransferrevisited
Xueliang Huang
Towardsmetal‐freearylations
With Xueliang Huang: J. Am. Chem. Soc. 2011, 133, 8510
Towardsmetal‐freearylations:enlargedscope
With Xueliang Huang, Mahendra Patil, Walter Thiel and Christophe Farès, J. Am. Chem. Soc. 2013, 135, 7312‐7323.
Mechanisticconsiderations
With Xueliang Huang, Mahendra Patil, Walter Thiel and Christophe Farès, J. Am. Chem. Soc. 2013, 135, 7312‐7323Cf: Procter, Angew.Chem. Int. Ed. 2013, 52, 4008 Ujaque and Asensio, Org. Lett. 2009, 11, 4906
Opportunitiesforfurtherchemistry?
With Bo Peng, Xueliang Huang and Langui Xie
Theimportanceofasulfoxide
With Bo Peng, Xueliang Huang and Langui XieCf: R. P. Hsung, Chem. Rev. 2010, 110, 5064
Tetrahedron 2006, 62, 3928
Keteniminiummeetssulfoxides
With Bo Peng, Xueliang Huang and Langui Xie, Angew. Chem. Int. Ed. 2014, 53, 8718(Selected as a Hot Paper by the Editorial Office)
Keteniminiummeetssulfoxides– again
RO R
NO
N
SR1
electrophilic activation PhS
R1
O
SO
R1
NR
N
OTf2O, several pyridine bases N
O
PhSPh2SO
nada
With Bo Peng and Danny Geerdink
First part of this lecture!
Keteniminiummeetssulfoxides– again
N
O
PhSN
O
PhS
N
O
PhSMeO
N
OPh
PhSN
O
PhS
N
O
PhS
N
O
PhS
ClN
O
PhS
90% 83%
84%
50% 76%
60%71% 75%
9 5
O
3 3
O
R1N
O
R3
R2R1
N
O
R3
R2
RS
O
PhS
MeO
O
78%
N
2-iodopyridine, Tf2O
0°C, 15 min. 0 °C to rt, 12 h
SR
O
O
NS
Me
O
NS
Me
Cl
O
NS
Bn
83% 64% 84%
With Bo Peng, Danny Geerdink and Christophe Farès, Angew. Chem. Int. Ed. 2014, 53, 5462(Selected as a VIP Article by the Editorial Office)
AmideActivation
Notonlysulfoxides– towardsageneralapproach? (Outlook)
Unpublished results (Bo Peng, Langui Xie, Daniel Kaiser, Mohan Padmanaban)
RO R
NO
N
SR1
electrophilic activation PhS
R1
O
SO
R1
NR
RO R
NO
N
XR1
electrophilic activation PhX
R1
O
XO
R1
NR
R1N
O
0 °C to rt, 24 h
NOH
Ph
O HNPh
O
N
O
HNPh
O
ClN
O
HNPh
O
3
64% 59%
R1N
O2-iodopyridine, Tf2O
0°C, 15 min.
N
O
HNPh
O
MeO
O
5
60%
Conversions to indoles and oxindoles: J. May, Org. Lett. 2013, 15, 1666T. Driver Org. Lett. 2014, 16, 2916
C‐Hfunctionalisation
C‐Hfunctionalisation
Redox‐neutralC‐Hfunctionalisation
Internal redox‐neutral C‐H activation + cyclisation
D. N. Reinhoudt J. Org. Chem. 1988, 53, 2278. M. Noguchi J. Chem. Soc., Perkin Trans. 1, 1998, 3327.D. Sames J. Am. Chem. Soc. 2005, 127, 12180 and Org. Lett. 2005, 24, 5419.Also cf: O. Meth‐Cohn, Adv. Heterocycl. Chem. 1972, 14, 211
Asymmetric catalysis:D. Seidel et al. J. Am. Chem. Soc. 2009, 131, 13226 D. Y. Kim et al. J. Am. Chem. Soc. 2010, 132, 11847T. Akiyama et al. J. Am. Chem. Soc. 2011, 133, 6166
AmineC‐Hfunctionalisation
Reviews on CDC coupling: C.‐J. Li, Acc. Chem. Res. 2009, 42, 335 C. J. Scheuermann, Chem. Asian J. 2010, 5, 436 M. Klussmann, D. Sureshkumar, Synthesis 2011, 3, 353
AmineC‐Hfunctionalisation:partI
Igor Jurberg, Eckhard Wöstefeld
AmineC‐Hfunctionalisation:partII
With Igor Jurberg, Bo Peng, Eckhard Wöstefeld and Maximilian Wasserloos, : Angew. Chem. Int. Ed. 2012, 51, 1950Angew. Chem. 2012, 124, 1986. (Hot Paper)
TotalSynthesisofIndolizidine167B
200 mg prepared in a single run
With Igor Jurberg, Bo Peng, Eckhard Wöstefeld and Maximilian Wasserloos, : Angew. Chem. Int. Ed. 2012, 51, 1950Angew. Chem. 2012, 124, 1986. (Hot Paper)
Conclusions
Amide activation methodologies
Development of a new Claisen‐like rearrangement
Versatile platform for the stereoselective synthesis of allyl and allenyl lactones
New avenues in Sulfur (IV) chemistry
Unconventional acess to and reactivity of sulfur ylides
Conclusions
New avenues in Sulfur (IV) chemistry
Direct arylations with sulfoxides
Conclusions
Conclusions
Part II: Organic Redox‐neutral reactions
Three‐stage amine C‐H functionalisation
Total Synthesis of Indolizidine 167B
Conclusions
Dr. Claire MadelaineViviana ValerioMaria Teresa OliveiraDr. Marco LupariaDr. Xueliang HuangDr. Davide AudisioDesislava PetkovaCaroline SourisSebastian KlimczykDr. Igor JurbergDr. Bo PengDr. Anais JolitMartina DrescherPatricia EmbergerVeronica Tona
Eckhard WöstefeldDr. Danny GeerdinkDr. Mohan PadmanabanDr. Daniel O‘DonovanRik OostSupaporn NiyomchonSaad ShaabanGerlinde GiessnerMartin BergerDr. Langui XieDr. Antonio MisaleDr. Aurélien de la TorreJuliette SabbataniDaniel Kaiser
Acknowledgement:TheMaulideGroup
