A New Chemoselective Base-Mediated Protection/Deprotection Method for Aldehydes

Synlett

Volumn , Issue 15, 2003, Pages 2317-2320

  Dixon, Darren J ^a   Scott, Mark S ^a   Luckhurst, Chris A ^b  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b ASTRAZENECA   (United Kingdom)

Author keywords

Aldehydes; Chemoselective; Protecting group; Pyrrole carbinol; Tandem reactions

Indexed keywords

ALDEHYDE; BUTYRALDEHYDE; KETONE; LITHIUM; LITHIUM PYRROLATE; METHANOL DERIVATIVE; METHOXIDE SODIUM; PYRROLE CARBINOL DERIVATIVE; PYRROLE DERIVATIVE; REAGENT; SILANE DERIVATIVE; TETRABUTYLAMMONIUM; TETRABUTYLAMMONIUM FLUORIDE; TETRAHYDROFURAN; UNCLASSIFIED DRUG;

ARTICLE; COLUMN CHROMATOGRAPHY; DEPROTECTION REACTION; HORNER WADSWORTH EMMONS REACTION; LITHIATION; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PROTON TRANSPORT; SILYLATION; SYNTHESIS; TEMPERATURE;

EID: 0347380050     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2003-42470     Document Type: Article

References (25)

1. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd ed; Wiley: New York, 1999.
2. Although cyanohydrins are formed under basic conditions, they are not always compatible with organometallic reagents and are normally used in their silyl ether form. Problems in their formation from conjugated aldehydes and ketone containing compounds can also occur see: Rawal, V. H.; Rao, J. A.; Cava, M. P. Tetrahedron Lett. 1985, 26, 4275; and references cited therein.
3. An imidazole/TBSC1 protection of aldehydes was recently reported where the adducts were deblocked using HF. See: Quan, L. G.; Cha, J. K. Synlett 2001, 1925.
4. -: Lee, S. D.; Brook, M. A.; Chan, T. H. Tetrahedron Lett. 1983, 24, 1569. (c) Brandänge, S.; Rodriguez, B. Acta Chem. Scand. Ser. B 1987, 41, 740. (d) Brandänge, S.; Holmgren, E.; Leijonmarck, H.; Rodriguez, B. Acta Chem. Scand. 1995, 49, 922. (e) Evans, D. A.; Borg, G.; Scheidt, K. A. Angew. Chem. Int. Ed. 2002, 41, 3188.
5. -: Lee, S. D.; Brook, M. A.; Chan, T. H. Tetrahedron Lett. 1983, 24, 1569. (c) Brandänge, S.; Rodriguez, B. Acta Chem. Scand. Ser. B 1987, 41, 740. (d) Brandänge, S.; Holmgren, E.; Leijonmarck, H.; Rodriguez, B. Acta Chem. Scand. 1995, 49, 922. (e) Evans, D. A.; Borg, G.; Scheidt, K. A. Angew. Chem. Int. Ed. 2002, 41, 3188.
6. -: Lee, S. D.; Brook, M. A.; Chan, T. H. Tetrahedron Lett. 1983, 24, 1569. (c) Brandänge, S.; Rodriguez, B. Acta Chem. Scand. Ser. B 1987, 41, 740. (d) Brandänge, S.; Holmgren, E.; Leijonmarck, H.; Rodriguez, B. Acta Chem. Scand. 1995, 49, 922. (e) Evans, D. A.; Borg, G.; Scheidt, K. A. Angew. Chem. Int. Ed. 2002, 41, 3188.
7. -: Lee, S. D.; Brook, M. A.; Chan, T. H. Tetrahedron Lett. 1983, 24, 1569. (c) Brandänge, S.; Rodriguez, B. Acta Chem. Scand. Ser. B 1987, 41, 740. (d) Brandänge, S.; Holmgren, E.; Leijonmarck, H.; Rodriguez, B. Acta Chem. Scand. 1995, 49, 922. (e) Evans, D. A.; Borg, G.; Scheidt, K. A. Angew. Chem. Int. Ed. 2002, 41, 3188.
8. -: Lee, S. D.; Brook, M. A.; Chan, T. H. Tetrahedron Lett. 1983, 24, 1569. (c) Brandänge, S.; Rodriguez, B. Acta Chem. Scand. Ser. B 1987, 41, 740. (d) Brandänge, S.; Holmgren, E.; Leijonmarck, H.; Rodriguez, B. Acta Chem. Scand. 1995, 49, 922. (e) Evans, D. A.; Borg, G.; Scheidt, K. A. Angew. Chem. Int. Ed. 2002, 41, 3188.
9. Note: Freshly distilled pyrrole was used. Distilled pyrrole will stay fresh for long periods if stored under Ar at -30°C.
10. The THF was rigorously degassed before use.
11. The reactions were carried out on a 10 mmol scale.
12. 4) and concentrated in vacuo to yield an oil which was purified by chromatography on silica gel.
13. 4e
14. Blanchette, M. A.; Choy, W.; Davis, J. T.; Essenfeld, A. P.; Masamune, S.; Roush, W. R.; Sakai, T. Tetrahedron Lett. 1984, 25, 2183.
15. Triethylphosphonoacetate (1.5 equiv) was deprotonated at 0°C in THF with n-BuLi (1.2 equiv), and the solution was then added to the pyrrole carbinol (1 equiv) at -78°C.
16. Synthesised in one step from 1-methyl-pent-1-ene, via ozonolysis in 70% yield. The aldehyde can be stored for short periods at -30°C under Ar.
17. 4Cl(aq).
18. 1H NMR (500 MHz).
19. The recovery of starting material is attributed to in situ protection of the keto group by intramolecular attack of the deprotonated pyrrole carbinol into the ketone.
20. Maurer, B.; Grieder, A.; Thommen, W. Helv. Chim. Acta 1979, 62, 44.
21. The in situ protection of aldehydes as amino alkoxides using lithium morpholide and lithium 2-[N-methyl-N-(2-pyridyl)]-amide nucleophiles was first studied by Comins et al. See as examples: (a) Comins, D. L.; Brown, J. D. Tetrahedron Lett. 1981, 22, 4213. (b) Comins, D. L.; Brown, J. D.; Mantlo, N. B. Tetrahedron Lett. 1982, 23, 3979. (c) Comins, D. L.; Brown, J. D. J. Org. Chem. 1984, 49, 1078.
22. The in situ protection of aldehydes as amino alkoxides using lithium morpholide and lithium 2-[N-methyl-N-(2-pyridyl)]-amide nucleophiles was first studied by Comins et al. See as examples: (a) Comins, D. L.; Brown, J. D. Tetrahedron Lett. 1981, 22, 4213. (b) Comins, D. L.; Brown, J. D.; Mantlo, N. B. Tetrahedron Lett. 1982, 23, 3979. (c) Comins, D. L.; Brown, J. D. J. Org. Chem. 1984, 49, 1078.
23. The in situ protection of aldehydes as amino alkoxides using lithium morpholide and lithium 2-[N-methyl-N-(2-pyridyl)]-amide nucleophiles was first studied by Comins et al. See as examples: (a) Comins, D. L.; Brown, J. D. Tetrahedron Lett. 1981, 22, 4213. (b) Comins, D. L.; Brown, J. D.; Mantlo, N. B. Tetrahedron Lett. 1982, 23, 3979. (c) Comins, D. L.; Brown, J. D. J. Org. Chem. 1984, 49, 1078.
24. 2D: 177.0899; found: 177.0894.
25. 13CNMR, HRMS, and IR.