In organic chemistry, 4-dimethylaminopyridine (DMAP) is defined as a base and a basic catalyst. It is mainly used to catalyze the acylation reaction and lactonization reaction of sterically hindered hydroxyl groups, and is also used to catalyze the silicon and etherification reactions of alcohols, etc. The catalytic properties of DMAP in organic chemistry have been reviewed in detail [1,2].
The acylation reaction of hydroxyl groups is one of the most important and frequent functional group conversion reactions in organic chemistry. In many cases, the acylation reaction can be easily completed by using an acylating reagent and an organic base or an inorganic base as an acid-binding reagent. However, when the hydroxyl-containing substrate molecule contains multiple functional groups, especially when some functional groups that are sensitive to acid or temperature exist, the reaction needs to be highly selective and carried out under mild conditions. Because the lone pair of electrons carried by the nitrogen atom on the dimethylamino group in the DMAP molecule resonates with the aromatic ring, the nucleophilicity of the nitrogen atom on the pyridine ring is increased. Therefore, DMAP, as an acylation transfer reagent, is 100 to 1,000,000 times faster than the acylation reaction catalyzed by pyridine. Generally speaking, DMAP is used as a catalyst, and the catalytic dosage is 0.05~0.2 mol. Most DMAP-catalyzed reactions can be completed within minutes to hours at room temperature and give high yields (Formula 1 and Formula 2) [3,4].
Under the catalysis of DMAP, the speed and yield of the direct esterification reaction of hydroxyl groups under the action of condensation reagents are significantly improved. For complex substrate molecules, the selectivity of the reaction is correspondingly improved. In the total synthesis route of natural products reported in literature [5], this reaction (Formula 3 and Formula 4) was used four times [5,6].
In the presence of DMAP, the phosphorylation, sulfonation and silicon etherification reactions of hydroxyl groups are all significantly catalyzed Effect. Therefore, many reactions that cannot be completed under normal reaction conditions or whose protecting groups will be damaged give satisfactory results under these conditions (Formula 5 to Formula 7) [7~9].
References
1. Scriven, E. F. V. Chem. Soc. Rev. 1983,12,129.
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2. Ragnarsson, U.; Grcn, L. Acc. Chem. Res. 1998,57,494.
3. Nicolaou, K. C.; Fylaktakidou, K. C.; Monenschein, H.; Li, Y.; Weyershausen, B.; Mitchell, H. J.; Wei,H.; Guntupalli, P.; Hepworth, D.; Sugita, K.J. Am. Cmethoxyphenylboronic acid hem. Soc. 2003, 125,15433.
4. Bonini, C.; Chiummiento, L.; PuJlez, M.; Solladic, G.; Colobert, F. J. Org. Chem. 2004, 69, 5015.
5. Ramachandran 2002,67,7547.
6. Pommier, A.; Stepanenko, V.; Jarowicki, K.; Kocienski, P. J. J. Org. Chem. . 2003, 68, 8.
7, Liao, X.; Wu, Y.; Brabander, J. K. D. Angew. Chem” Int. Ed. 2003, 42, 1648.
8. Ruiz, P.; Murga, J.; Carda, M.; Marco, J. A. J. Org. Chem. 2005,10, 713.
9. Burova, S. A,; McDonald, F. E. J. Am . Chem. Soc. 2004,126,2495.
