- Reagent Availability
- Experimental User Friendliness
-Benzyl group (Bn) is stable towards both acids and bases and is a highly general protecting group.
-Base sensitive compounds can be protected using BnOC(=NH)CCl3 under acidic conditions.
-Deprotection is usually done under reductive conditions (H2-Pd/C, Na/NH3(l), electrolytic reduction, etc). Alternatively, benzyl groups can be deprotected by RuCl3/NaIO4 oxidation-then-hydrolysis or by the combination of a Lewis acid and a nucleophile (such as Me2BBr).
・Czernecki, S.; Georgoulis, C.; Provelenghiou, C. Tetrahedron Lett. 1976, 17, 3535. doi:10.1016/S0040-4039(00)71351-7
・White, J. D.; Reddy, G. N.; Spessard, G. O. J. Am. Chem. Soc. 1988, 110, 1624. DOI: 10.1021/ja00213a047
Follows the mechanism of Williamson ether synthesis.
Typical protection and deprotection examples: Benzyl group is stable, therefore protection is often done during the early stage of syntheses.
Selective cleavage of N-Bn in the presence of O-Bn is possible.
The Dudley reagent: This bench stable reagent is easy to handle and capable of benzylation under nearly neutral conditions.
-The substrate is reacted with BnCl or BnBr in DMF with NaH as a base. Benzylated products are generally obtained in high yield.
-The catalytic addition of Bu4NI (TBAI) or NaI accelerates benzylation (through in situ formation of reactive BnI).
-Benzyl bromide is a lachrymator. Handle it inside a fume hood.
-Quenching the reaction with methanol/potassium carbonate instead of water is a nice way to destroy unreacted benzyl bromide. This procedure is recommended as it makes extraction easier.
 Oguri, H.; Hishiyama, S.; Oishi, T.; Hirama, M. Synlett 1995, 1252. DOI: 10.1055/s-1995-5259
 Kroutil, J.; Tmka, T.; Cemy, M. Synthesis 2004, 446. DOI: 10.1055/s-2004-815937
 (a) Poon, K. W. C.; Dudley, G. B. J. Org. Chem. 2006, 71, 3923. DOI: 10.1021/jo0602773 (b) Poon, K. W. C.; House, S. E.; Dudley, G. B. Synlett 2005, 3142. DOI: 10.1055/s-2005-921898