Efficient and Selective Cleavage of t-Butoxycarbonyl Group from Carbamates and Amides by CeCl₃·7H₂O-NaI

Abstract

A highly selective cleavage of the t-butoxycarbonyl group has been achieved in high yields using CeCl₃·7H₂O-NaI in acetonitrile at ambient temperature under neutral conditions. This method is mild and compatible with a wide range of functional groups such as THP, TBDMS, TBDPS, trityl ethers, mono-BOC or Cbz protected amines, acetamide, sulfonamide and benzamide etc., present in the substrate.

Key words

cerium reagents - carbamates - amides - α-amino acids

References

• 1a Greene TW. Wuts PGM. Protective Groups in Organic Synthesis, 3rd ed.   John Wiley and Sons; New York: 1999. 
• 1b Kocienski PJ. Protecting Groups   Thieme; Stuttgart: 1994. 
• 2a Gunnarsson K. Grehn L. Ragnarsson U. Angew. Chem., Int. Ed. Engl.  1988,  27:  400 
• 2b Carpino LA. Mansour EME. El-Faham A. J. Org. Chem.  1993,  58:  4162 
• 3a Campbell JA. Hart DJ. J. Org. Chem.  1993,  58:  2900 
• 3b Koppel I. Koppel J. Degerback F. Ragnarsson U. J. Org. Chem.  1991,  56:  7172 
• 4a Gibson MS. Bradshaw RW. Angew Chem., Int. Ed. Engl.  1968,  7:  919 
• 4b Ragnarsson U. Grehn L. Acc. Chem. Res.  1991,  24:  285 
• 5a Kokotos G. Padron JM. Martin T. Gibbons WA. Martin VS. J. Org. Chem.  1998,  63:  3741 
• 5b Burk MJ. Allen JG. J. Org. Chem.  1997,  62:  7054 
• 5c Sugawara N. Stevens ES. Bonora GM. Toniolo C. J. Am. Chem. Soc.  1980,  102:  7044 
• 6a Connell RD. Rein T. Akermark B. Helquist P. J. Org. Chem.  1988,  53 
• 6b Brosse N. Pinto M.-F. Gregoire BJ. Tetrahedron Lett.  2000,  41:  205 
• 7a Allan RD. Johnston GA. Kazlauskas R. Tran HW. J. Chem. Soc., Perkin Trans. 1  1983,  2983 
• 7b Carpino LA. J. Org. Chem.  1964,  29:  2820 
• 7c Stafford JA. Brackeen MF. Karanewsky DS. Valvano NL. Tetrahedron Lett.  1993,  34:  7873 
• 8a Kobayashi S. Synlett  1994,  689 
• 8b Kobayashi S. Eur. J. Org. Chem.  1999,  15 
• 9a Bartoli G. Bosco M. Marcantoni E. Sambri L. Torregiani E. Synlett  1998,  209 
• 9b Bartoli G. Bellucci MC. Bosco M. Cappa A. Marcantoni E. Sambri L. Orregiani E. J. Org. Chem.  1999,  64:  5696 
• 9c Marcantoni E. Nobili F. Bartoli G. Bosco M. Sambri L. J. Org. Chem.  1997,  62:  4183 
• 9d Yadav JS. Reddy BVS. Synlett  2000,  1275 

10

Experimental Procedure: A mixture of di-BOC derivative (5 mmol), CeCl₃·7 H₂O (5 mmol) and sodium iodide (5 mmol) in acetonitrile (10 mL) was stirred at ambient temperature for an appropriate time (Table). After complete conversion, as indicated by TLC, the reaction mixture was diluted with water (25 mL) and extracted with ethyl acetate (2 × 20 mL). The combined organic layers were washed with brine, dried over anhyd Na₂SO₄ and concentrated in vacuo, and the resulting product was purified by column chromatography on silica gel (Merck, 100-200 mesh, ethyl acetate-hexane, 2:8) to afford pure mono-BOC protected amine. Spectroscopic Data of 1a: [α]_D ²⁵ = -38.2 (c 1.5, CHCl₃). ¹H NMR (CDCl₃): δ = 1.45 (s, 18 H), 3.60 (dd, 2 H, J = 5.5, 13.6 Hz), 3.65 (s, 3 H), 5.38 (dd, 1 H, J = 5.5, 10.3 Hz), 7.28-7.42 (m, 15 H). 2a: [α]_D ²⁵ = +11.3 (c 1.5, CHCl₃). ¹H NMR (CDCl₃): δ = 1.40 (s, 9 H), 3.38 (dd, 2 H, J = 5.5, 13.6 Hz), 3.75 (s, 3 H), 4.38 (m, 1 H), 5.35 (brd, NH, J = 8.0 Hz), 7.10-7.40 (m, 15 H). 1b: [α]_D ²⁵ = -29.789 (c 1.5, CHCl₃). ¹H NMR (CDCl₃): δ = 0.03 (s, 6 H), 0.85 (s, 9 H), 1.48 (s, 18 H), 3.67 (s, 3 H), 4.10 (dd, 2 H, J = 5.8, 13.7 Hz), 5.10 (dd, 1 H, J = 5.8 and 10.5 Hz). 2b: [α]_D ²⁵ = +17.684 (c 1.5, CHCl₃). ¹H NMR (CDCl₃): δ = 0.02 (s, 6 H), 0.84 (s, 9 H), 1.43 (s, 9 H), 3.75 (s, 3 H), 3.80 (dd, 1 H, J = 5.8, 13.7 Hz), 4.05 (dd, 1 H, J = 5.8, 13.7 Hz), 4.30 (m, 1 H), 5.23 (brd, NH, J = 7.8 Hz). 1d: [α]_D ²⁵ = -11.8 (c 1.5, CHCl₃). ¹H NMR (CDCl₃): δ = 1.03 (s, 9 H), 1.43 (s, 18 H), 3.62 (s, 3 H), 4.18 (dd, 2 H, J = 5.7, 13.8 Hz), 5.23 (dd, 1 H, J = 5.7, 10.3 Hz), 7.38-7.40 (m, 6 H), 7.58-7.65 (m, 4 H). 2d: [α]_D ²⁵ = +14.2 (c 1.5, CHCl₃). ¹H NMR (CDCl₃): δ = 1.0 (s, 9 H), 1.45 (s, 9 H), 3.78 (s, 3 H), 3.98 (dd, 2 H, J = 5.7, 13.8 Hz), 4.38 (m, 1 H), 5.32 (br d, NH, J = 8.3 Hz), 7.28-7.43 (m, 6 H), 7.5-7.63 (m, 4 H). 1h: [α]_D ²⁵ = -35.57 (c 1.0, CHCl₃). ¹H NMR (CDCl₃): δ = 1.48 (s, 18 H), 2.10 (s, 3 H), 2.43-2.60 (m, 4 H), 3.78 (s, 3 H), 5.05 (dd, 1 H, J = 9.0 and 4.5 Hz). 2h: [α]_D ²⁵ = 24.3 (c 2.8, CHCl₃), (ref. [5] [α]_D ²⁵ = 24.6 (c 2.84, CHCl₃)). ¹H NMR (CDCl₃): δ = 1.33 (s, 9 H), 1.78-1.90 (m, 2 H), 1.98 (s, 3 H), 2.41 (t, 2 H, J = 7.3 Hz), 3.65 (s, 3 H), 4.32-4.41 (m, 1 H), 5.23 (br s, NH). 1j: [α]_D ²⁵ = +12.8 (c 1.0, CHCl₃). ¹H NMR (CDCl₃): δ = 0.88 (d, 3 H, J = 6.8 Hz), 1.18 (d, 3 H, J = 6.8 Hz), 1.50 (s, 18 H), 2.42-2.50 (m, 1 H), 3.78 (s, 3 H), 4.48 (d, 1 H, J = 6.8 Hz). 2j: [α]_D ²⁵ = -20.8 (c 1.1, MeOH) (ref. [5] [α]_D ²⁵ = -21.2 (c 1.1, MeOH)). ¹H NMR (CDCl₃): δ = 0.85 (d, 3 H, J = 6.8 Hz), 0.90 (d, 3 H, J = 6.8 Hz), 1.50 (s, 9 H), 2.02-2.18 (m, 1 H), 3.75 (s, 3 H), 4.23 (m, 1 H), 4.95 (brs, NH). 1l: [α]_D ²⁵ = -37.2 (c 2.15, CHCl₃), (ref. [5] [α]_D ²⁵ = -37.2 (c 2.15, CHCl₃)). ¹H NMR (CDCl₃): δ = 1.50 (s, 18 H), 2.18 (m, 1 H), 2.40 (m, 2 H), 2.45 (m, 1 H), 3.68 (s, 3 H), 3.75 (s, 3 H), 4.95 (dd, 1 H, J = 9.0 and 4.3 Hz). 2l: [α]_D ²⁵ = +12.7 (c 2.00, CHCl₃), [ref. [5] [α]_D ²⁵ = +12.9 (c 2.00, CHCl₃)]. ¹H NMR (CDCl₃): δ = 1.40 (s, 9 H), 1.90 (m, 1 H), 2.15 (m, 1 H), 2.39 (m, 2 H), 3.65 (s, 3 H), 3.70 (s, 3 H), 3.40 (br s, 1 H), 5.15 (br s, NH). IICT Commun. No: 01/x/10.