Sulfonyl-1,2,3-Triazoles : Convenient Synthones for Heterocyclic Compounds

Zibinsky, M. and Fokin, V. V. Angew. Chem. Int. Ed. 2013 ,

52

, 1507-1510.

Michaël Raymond Literature Meeting Presentation Université de Montréal October 16

th

, 2013

Valery V. Fokin

1. Associate Professor at The Scripps Research Institute – La Jolla, California 2. B. Sc. Calvin College, Geneva, in 1993 3. M. Sc. University of Nizhny Novgorod, Russia 4. Ph. D. University of Southern California in 1998 5. Post-Doc with K. Barry Sharpless from 1999 2001 at The Scripps Research Institute – La Jolla, California 6. Author with K. Barry Sharpless and M. G. Finn of the ‘’Click Chemistry’’ 7. Author of more than 60 publications in the past 10 years 2

Research Interests

1. Discovery of new catalytic transformations and applying them to the studies of macromolecular and biological phenomena.

2. Studies on the Copper-Catalysed Azide-Alkyne Cycloaddition (CuAAC) and the Ruthenium-Catalysed Azide-Alkyne Cycloadditon (RuAAC), or ‘’Click Reaction’’.

3. Catalytic transformations of 1,2,3-triazoles which proceeds via transition metal aza-vinyl carbene species.

4. Studies of dendrimers and dendritic probes for cellular and organismal imaging and targeted drug delivery.

5. Discovery of novel polymeric materials.

3

1,2,3-Triazoles

1. Robust heterocyclic aromatic molecules.

2. Stable to thermal decomposition.

3. Stable to oxidative and reductive conditions.

4. Building blocks for many pharmaceutical drugs such as tazobactam. (a) Shafran, E. A.; Bakulev, V. A.; Rozin, Y. A. and Shafran, Y. M.

L.; Li, Y. Z.; Zhang, Q. S. and Zhu, H. S.

J. Synth. Org. Chem. 2005 Chem. Heterocycl. Comp. 2008, 44 ,

3

, 442.

, 1040. (b) Xu, W.

4

1,2,3-Triazoles Synthesis

1. Huisgen 1,3-dipolar cycloaddition of alkynes to azides is a basic synthetic route to triazoles but elevated temperatures and mixtures of regioisomers obtained limit its application.

2. Copper Catalyzed Azide-Alkyne Cycloaddition (CuAAC), known as ‘Click’ reaction, first developed by Sharpless served to reinvigorated research interest in triazoles synthesis and helped to acquired regioselectivity and expand the scope of the substitutions around the triazole ring system.

(a) Huisgen, R.

1,3-Dipolar Cycloaddition Chemistry

(Ed.: Padwa, A.) Wiley, New-York,

1984

, pp 1-176. (b) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V. and Sharpless, K. B.

Angew. Chem. Int. Ed. 2002 , Hilgraf, R.; Rostovstev, V. V.; Noodleman, L.; Sharpless, K. B. and Fokin, V. V.

41

, 2596-2599. (c) Himo, F.; Lovell, T.; J. Am. Chem. Soc. 2005 ,

127

, 210-216.

5

Click Mechanism

Rostovtsev, V. V.; Green, L. G.; Fokin, V. V. and Sharpless, K. B.

Worrell, B. T. and Fokin, V. V.

Science

,

2013

,

340

, 457-460.

Angew. Chem. Int. Ed. 2002 ,

41

, 2596-2599. (b) 6

1,2,3-Triazoles Ring Opening

1. Electron withdrawing groups on N1 such as cyano, nitro or sulfonyl are known to favor opening of stable 1,2,3-triazoles to its diazoimine tautomers.

2. Diazoketones are more stable than diazoimines.

3. Sulfonylazides give access to an easily opened 1,2,3-triazole ring system.

(a) Dimroth, O.

Johnson, J.

Ann. 1909 ,

364

, 183. (b) Gilchrist, T. L. and Gymer, G. E.

(c) Raushel, J. and Fokin, V. V.

J. Org. Chem. 1970 , Org. Lett. 2010

35

, 3444-3448.

, Adv. Heterocycl. Chem. 1974 ,

16

, 33.

12

, 4952-4955. (d) Harmon, R. E.; Stanley, F. J.; Gepta, S. and 7

Metal Carbenoids from Vinyl Diazoimines

1. Equilibrium of 2-pyridyl diazo compounds bearing an electron withdrawing group from their cyclic triazole form allows transformations characteristic of diazoketones.

2. 1-Sulfonyl triazoles : precursors to metal carbenoids which are synthetic equivalents of α-diazoaldehydes.

3. Fokin ’s utilization of sulfonyl triazoles in synthesis : Transannulation with nitriles (a) Regitz, M.

Angew. Chem. Int. Ed. 1967 Int. Ed. 2007 , 46, 4757-4759. (c) Fu, G. C. In Weinheim, Germany,

2005

Modern Rhodium Catalsed Organic Reactions

; Evans, D. A., Ed.; VCH; , pp. 79. (d) Horneff, T.; Chuprakov, S.; Chernyak, N.; Gevorgyan, V. and Fokin, V. V.

J. Am.

Chem Soc. 2008 ,

130

, 14972-14974.

,

79

, 786. (b) Chuprakov, S.; Hwang, F. W. and Gevorgyan, V.

Angew. Chem.

8

Mechanism of Transannulation of 1,2,3-Triazoles with Nitriles

1. Rh-carbene catalyzed ring opening and azavinyl carbene formation 2. Path A 3. Path B : 3+2 cycloaddtion Horneff, T.; Chuprakov, S.; Chernyak, N.; Gevorgyan, V. and Fokin, V. V.

J. Am. Chem Soc. 2008 ,

130

, 14972-14974.

9

Applications of Metal Vinyl Carbenoids

1. Cyclopropanation of olefins.

2. Nickel(0)-catalyzed alkyne insertions.

3. Asymmetric C-H insertions.

(a) Chuprakov, S.; Kwok, S. W.; Zhang, L.; Lercher, L. and Fokin, V. V.

J. Am. Chem. Soc. 2009 ,

131

, 18034-18035. (b) Miura, T.; Yamauchi, M. and Murakami, M.

M. and Fokin, V. V.

J. Am. Chem. Soc. 2011 Chem. Commun. 2009 ,

133

, 10352-10355.

, 1470-1471. (c) Chuprakov,, S.; Malik, J. A.; Zibinsky, 10

1,3-Dipolar Cycloadditions Versus Intramolecular Cyclization : This Work

1. Reactivity expected with a rhodium catalyst : 1,3-dipolar cycloaddition.

2. New Reactivity : Intramolecular Cyclization to form 3-sulfonyl-4-oxazolines and 1,2,5 trisubstituted imidazoles.

De Angelis, A.; Taylor, M. T. and Fox, J. M.

J. Am. Chem. Soc. 2009 ,

131

,1101-1105.

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Optimization of the Reaction for the Synthesis of 3-Sulfonyl-4-Oxazolines Entry

1 2 6 7 8 3 4 5

R 5

Me Me Me Me Me Me C 6 H 4 Me C 6 H 4 Me

Catalyst

Rh 2 (oct) 4 Rh 2 (piv) 4 Rh 2 (piv) 4 Rh 2 ((

S

)-nttl) 4 Rh 2 ((

S

)-nttl) 4 Rh 2 ((

S

)-ptad) 4 Rh 2 ((

S

)-nttl) 4 Rh 2 ((

S

)-ptad) 4

Temp.

( ( o C)

100 100 RT RT 40 RT RT

Time

0.15

0.15

12 12 9 12 48

Yield

61 83 82 75 80 70 ‹50

ee

88 73 45 12

Reaction Scope for 3-Sulfonyl-4-Oxazolines with Respect to R 2

13

Reaction Scope for 3-Sulfonyl-4-Oxazolines with Respect to R 1 Entry

1 2 3 4 5 6

R 1

Ph 4-CF 3 C 6 H 4 4-MeC 6 H 4 4-MeOC 6 H 4 3-thiophenyl

n

-C 5 H 11

Yield (%)

85 86 97 93 91 Trace

Ee

(%)

92 92 94 88 80 14

Mechanism for 3-Sulfonyl-4-Oxazolines Synthesis

Prolonged reaction times reduce enantioselectivity 15

Mechanism for 1,2,5-Trisubstituted Imidazoles Synthesis

16

Reaction Scope for 1,2,5-Trisubstituted Imidazoles

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Conclusions

1. Development of a new asymmetric intramolecular cyclization to form 3 sulfonyl-4-oxazolines using a rhodium catalyzed ring opening of sulfonyl-1,2,3 triazoles giving high yields and ee.

2. Development of a new asymmetric intramolecular cyclization to form 1,2,5 sulfonyl imidazoles using a rhodium catalyzed ring opening of sulfonyl-1,2,3 triazoles giving high yields.

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