Control of Site of Lithiation of 3-(Aminomethyl)pyridine Derivatives

Keith Smith; Gamal A. El-Hiti; Mohammed B. Alshammari; Ahmed Fekri

doi:10.1055/s-0033-1338547

Synthesis, Table of Contents

Synthesis 2013; 45(24): 3426-3434
DOI: 10.1055/s-0033-1338547

paper

Control of Site of Lithiation of 3-(Aminomethyl)pyridine Derivatives

Keith Smith*

^aSchool of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, UK Fax: +44(29)20870600 Email: smithk13@cardiff.ac.uk

,

Gamal A. El-Hiti*

^bDepartment of Optometry, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia Email: gelhiti@ksu.edu.sa

,

Mohammed B. Alshammari

^aSchool of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, UK Fax: +44(29)20870600 Email: smithk13@cardiff.ac.uk

,

Ahmed Fekri

^aSchool of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, UK Fax: +44(29)20870600 Email: smithk13@cardiff.ac.uk

› Author Affiliations

Abstract

All articles of this category

Abstract

Lithiation of N-(pyridin-3-ylmethyl)pivalamide, tert-butyl N-(pyridin-3-ylmethyl)carbamate, and N,N-dimethyl-N′-(pyridin-3-ylmethyl)urea with tert-butyllithium (3 equiv) in anhydrous tetrahydrofuran at –78 °C takes place on the nitrogen and on the ring at the 4-position. The dilithium reagents thus obtained react with various electrophiles to give the corresponding substituted derivatives in high yields. On the other hand, regioselective side-chain lithiation occurs with lithium diisopropylamide (3.3 equiv) at –20 to 0 °C. A mixture of ring and side-chain substitution products is obtained with n-butyllithium as the lithium reagent. Treatment of one of the ring-substituted products with trifluoroacetic anhydride in dichloromethane under reflux conditions led to formation of the corresponding 1H-pyrrolo[3,4-c]pyridine in high yield.

Key words

directed lithiation - side-chain lithiation - N-(pyridin-3-ylmethyl)pivalamide - N,N-dimethyl-N′-(pyridin-3-ylmethyl)urea - tert-butyl N-(pyridin-3-ylmethyl)carbamate

Full Text

References

References and Notes
1 Current address: Chemistry Department, College of Sciences and Humanities, Salman bin Abdulaziz University, P.O. Box 83, Al-Kharij 11942, Saudi Arabia.
2 Current address: Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt.

See, for example:

3a Clayden J. Organolithiums: Selectivity for Synthesis. Pergamon; Oxford: 2002
3b Schlosser M. Organometallics in Synthesis . 2nd ed. Wiley; Chichester: 2002: 1-352
3c El-Hiti GA. Heterocycles 2000; 53: 1839
3d Mongin F, Quéguiner G. Tetrahedron 2001; 57: 4059
3e Turck A, Plé N, Mongin F, Quéguiner G. Tetrahedron 2001; 57: 4489
3f Anctil EJ.-G, Snieckus V. J. Organomet. Chem. 2002; 653: 150
3g Smith K, El-Hiti GA. Curr. Org. Synth. 2004; 1: 253
3h Chinchilla R, Nájera C, Yus M. Chem. Rev. 2004; 104: 2667
3i Schlosser M. Angew. Chem. Int. Ed. 2005; 44: 376
3j Foubelo F, Yus M. Curr. Org. Chem. 2005; 9: 459
3k Rathman TL, Bailey WF. Org. Process Res. Dev. 2009; 13: 144
3l Florio S, Aggarwal V, Salomone A. Org. Lett. 2004; 6: 4191
3m Capriati V, Florio S, Luisi R. Chem. Rev. 2008; 108: 1918
3n Florio S, Capriati V, Salomone A. Top. Stereochem. 2010; 26: 135
3o Houlden CE, Lloyd-Jones GC, Booker-Milburn KI. Org. Lett. 2010; 12: 3090
3p Volz N, Clayden J. Angew. Chem. Int. Ed. 2011; 50: 12148
3q El-Hiti GA, Hegazy AS, Alotaibi MH, Ajarim MD. ARKIVOC 2012; (vii): 35

Recent examples for substituted benzenes:

4a Clayden J, Turner H, Pickworth M, Adler T. Org. Lett. 2005; 7: 3147
4b Clayden J, Dufour J. Tetrahedron Lett. 2006; 47: 6945
4c Burgos PO, Fernández I, Iglesias MJ, García-Granda S, Ortiz FL. Org. Lett. 2008; 10: 537
4d Porcs-Makkay M, Komáromi A, Lukács G, Simig G. Tetrahedron 2008; 64: 1029
4e Michon C, Murai M, Nakatsu M, Uenishi J, Uemura M. Tetrahedron 2009; 65: 752
4f Tilly D, Fu J.-M, Zhao B.-P, Alessi M, Catanet A.-S, Snieckus V, Mortier J. Org. Lett. 2010; 12: 68
4g Slocum DW, Wang S, White CB, Whitley PE. Tetrahedron 2010; 66: 4939
4h Cho I, Meimetis L, Belding L, Katz MJ, Dudding T, Britton R. Beilstein J. Org. Chem. 2011; 7: 1315
4i Schmid M, Waldner B, Schnürch M, Mihovilovic MD, Stanetty P. Tetrahedron 2011; 67: 2895
4j Page A, Clayden J. Beilstein J. Org. Chem. 2011; 7: 1327
4k Coppi DI, Salomone A, Perna FM, Capriati V. Angew. Chem. Int. Ed. 2012; 51: 7532

Recent examples for substituted heterocycles:

5a Robert N, Bonneau A.-L, Hoarau C, Marsais F. Org. Lett. 2006; 8: 6071
5b Comoy C, Banaszak E, Fort Y. Tetrahedron 2006; 62: 6036
5c Luisi R, Capriati V, Florio S, Musio B. Org. Lett. 2007; 9: 1263
5d Clayden J, Hennecke U. Org. Lett. 2008; 10: 3567
5e McLaughlin M, Marcantonio K, Chen C, Davies IW. J. Org. Chem. 2008; 73: 4309
5f Capriati V, Florio S, Luisi R, Mazzanti A, Musio B. J. Org. Chem. 2008; 73: 3197
5g Affortunato F, Florio S, Luisi R, Musio B. J. Org. Chem. 2008; 73: 9214
5h Musio B, Clarkson GJ, Shipman M, Florio S, Luisi R. Org. Lett. 2009; 11: 325
5i Capriati V, Florio S, Perna FM, Salomone A. Chem. Eur. J. 2010; 16: 9778
5j Perna FM, Salomone A, Dammacco M, Florio S, Capriati V. Chem. Eur. J. 2011; 17: 8216
5k Coppi DI, Salomone A, Perna FM, Capriati V. Chem. Commun. 2011; 47: 9918
5l Clayton J, Clayden J. Tetrahedron Lett. 2011; 52: 2436
5m Ibrahim N, Chevot F, Legraverend M. Tetrahedron Lett. 2011; 52: 305
5n Sheikh NS, Leonori D, Barker G, Firth JD, Campos KR, Meijer AJ. H. M, O’Brien P, Coldham I. J. Am. Chem. Soc. 2012; 134: 5300

6a Smith K, El-Hiti GA, Abdo MA, Abdel-Megeed MF. J. Chem. Soc., Perkin Trans. 1 1995; 1029
6b Smith K, El-Hiti GA, Abdel-Megeed MF, Abdo MA. J. Org. Chem. 1996; 61: 647
6c Smith K, El-Hiti GA, Abdel-Megeed MF, Abdo MA. J. Org. Chem. 1996; 61: 656
6d Smith K, El-Hiti GA, Pritchard GJ, Hamilton A. J. Chem. Soc., Perkin Trans. 1 1999; 2299
6e Smith K, El-Hiti GA, Shukla AP. J. Chem. Soc., Perkin Trans. 1 1999; 2305
6f Smith K, El-Hiti GA, Hawes AC. Synthesis 2003; 2047
6g Smith K, El-Hiti GA, Mahgoub SA. Synthesis 2003; 2345
6h El-Hiti GA. Synthesis 2003; 2799
6i Smith K, El-Hiti GA, Abdel-Megeed MF. Synthesis 2004; 2121
6j El-Hiti GA. Synthesis 2004; 363
6k Smith K, El-Hiti GA, Hegazy AS. J. Sulfur Chem. 2005; 26: 121
6l Smith K, El-Hiti GA, Hegazy AS. Synthesis 2005; 2951
6m Smith K, Barratt ML. J. Org. Chem. 2007; 72: 1031

7 Smith K, El-Hiti GA, Hegazy AS. Synlett 2009; 2242
8 Smith K, El-Hiti GA, Hegazy AS, Fekri A, Kariuki BM. ARKIVOC 2009; (xiv): 266
9 Smith K, El-Hiti GA, Hegazy AS. Synthesis 2010; 1371
10 Smith K, El-Hiti GA, Alshammari MB. Synthesis 2012; 44: 2013
11 Smith K, El-Hiti GA, Alshammari MB. J. Org. Chem. 2012; 77: 11210
12 Smith K, El-Hiti GA, Alshammari MB. Synlett 2013; 24: 117
13 Smith K, El-Hiti GA, Hegazy AS, Fekri A. Heterocycles 2010; 80: 941
14 Smith K, El-Hiti GA, Hegazy AS. Chem. Commun. 2010; 46: 2790
15 Smith K, El-Hiti GA, Hegazy AS, Kariuki B. Beilstein J. Org. Chem. 2011; 7: 1219

16a Padwa A, Bur S. Chem. Rev. 2004; 104: 2401
16b Kodama T, Tamura M, Oda T, Yamazaki Y, Nishikawa M, Takemura S, Doi T, Kyotani Y, Ohkuchi M. US 6605620B1, 2003
16c Katritzky AR, Pozharskii AF. Handbook of Heterocyclic Chemistry . 2nd ed. Pergamon Press; New York: 2000
16d Craig PN. Cumulative subject index and drug compendium. In Comprehensive Medicinal Chemistry . Vol. 6. Hansch C, Sammes PG, Taylor JB. Pergamon Press; Oxford: 1990

17 Fraser RR, Baignee A, Bresse M, Hata K. Tetrahedron Lett. 1982; 23: 4195
18 Marasais F, Quéguiner G. Tetrahedron 1983; 39: 2009
19 Hosomi A, Ando M, Sakurai H. Chem. Lett. 1984; 1385
20 Comins DL, LaMunyon DH. Tetrahedron Lett. 1988; 29: 773
21 Galiano-Roth AS, Kim YJ, Gilchrist JH, Harrison AT, Fuller DJ, Collum DB. J. Am. Chem. Soc. 1991; 113: 5053
22 Romesberg FE, Collum DB. J. Am. Chem. Soc. 1992; 114: 2112
23 Olofson RA, Dougherty CM. J. Am. Chem. Soc. 1973; 95: 582
24 Taylor SL, Lee DY, Martin JC. J. Org. Chem. 1983; 48: 4156
25 Fraser RR, Bresse M, Mansour TS. J. Chem. Soc., Chem. Commun. 1983; 620
26 Hall PL, Gilchrist JH, Collum DB. J. Am. Chem. Soc. 1991; 113: 9571
27 Plé N, Turk A, Martin P, Barbey S, Quéguiner G. Tetrahedron Lett. 1993; 34: 1605

28a Güngör T, Marsais F, Quéguiner G. Synthesis 1982; 499
28b Pomel V, Rovera JC, Godard A, Marsais F, Quéguiner G. J. Heterocycl. Chem. 1996; 33: 1995
28c Godard A, Rocca P, Pomel V, Thomas-dit-Dumont L, Rovera J.-C, Thaburet J.-F, Marsais F, Quéguiner G. J. Organomet. Chem. 1996; 517: 25
28d Pollet P, Turck A, Plé N, Quéguiner G. J. Org. Chem. 1999; 64: 4512
28e Choppin S, Gros P, Fort Y. Eur. J. Org. Chem. 2001; 603
28f Woltermann CJ, Schwindeman JA. PharmaChem 2002; 1: 5 ; Chem. Abstr. 2004, 140, 94077

29a Turner JA. J. Org. Chem. 1983; 48: 3401
29b Smith K, Anderson D, Matthews I. Sulfur Lett. 1995; 18: 79
29c Gros P, Choppin S, Mathieu J, Fort Y. J. Org. Chem. 2002; 67: 234
29d Lazaar J, Rebstock A.-S, Mongin F, Godard A, Trécourt F, Marsais F, Quéguiner G. Tetrahedron 2002; 58: 6723

30a Smith K, Lindsay CM, Morris IK, Matthews I, Pritchard GJ. Sulfur Lett. 1994; 17: 197
30b Watson SE, Markovich A. Heterocycles 1998; 48: 2149
30c Numata A, Kondo Y, Sakamoto T. Synthesis 1999; 306

31 Khartabil HK, Gros PC, Fort Y, Ruiz-López MF. J. Am. Chem. Soc. 2010; 132: 2010

For discussion of aggregation level, see:

32a Williard PG, Li W, Kagan G, Hopson R. ARKIVOC 2011; (v): 180
32b Bauer W, Winchester WR, Schleyer von R. P. Organometallics 1987; 6: 2371

33 Smith K, El-Hiti GA, Fekri A, Alshammari MB. Heterocycles 2012; 86: 391
34 Watson SC, Eastham JF. J. Organomet. Chem. 1967; 9: 165

Supplementary Material

Supporting Information