Rearrangements 4-dimethylaminopyridine

Dimethylaminopyridine [1122-58-3] (DMAP) (24) has emerged as the preferred catalyst for a variety of synthetic transformations under mild conditions, particularly acylations, alkylations, silylations, esterifications, polymeri2ations, and rearrangements (100). POLYDMAP resin [1122-58-3], a polymeric version of DMAP, is available, and is as effective as DMAP as a catalyst for acylation reactions. Furthermore, it can be recycled without regeneration more than 20 times with very Htde loss in activity. POLYDMAP is a trademark of Reilly Industries, Inc. 

In 1970 Steglich and Hofle reported that 4-dimethylaminopyridine (DMAP) and 4-(pyrrolidino)pyridine (PPY) are excellent catalysts for isomerization of O-acyl azlactones E to their C-acylated isomers F [79-81], In this rearrangement, a new quaternary stereocenter is generated (Scheme 13.41). Clearly, DMAP or PPY afford the rearrangement products F in the racemic form. 

Tabuchi, H., Hamamoto, T., Ichihara, A. Modification of the Fries type rearrangement of the O-enol acyl group using W,W-dicyclohexylcarbodiimide and 4-dimethylaminopyridine. Synlett 1993, 651-652. 

En route to a total synthesis of the anticancer compound FR901464, Koide and coworkers carried out a diastereoselective allylic selenoxide rearrangement upon oxidation of either allyl selenide 251 [Scheme 18.641. Optimization studies using the preformed allyl selenide 251 identified the o-nitrophenyl selenide as an effective aryl substituent and N,N-dimethylaminopyridine as the best selenophilic base additive in the formation of rearrangement product 252 (see top of Scheme 18.641. Reactions were slower and diastereoselectivity, a crucial parameter here, was lower using other bases or with less than 3 equiv of DMAP. Using the optimized conditions, a one-pot method for overall 1,3-allylic alcohol transposition was... 

This case study highlights the formidable challenge posed by epimerization en route to the synthesis of nonpeptidic fragments of cyclic peptide natural products. (3S,4R,7S)-HTMMD was prepared from (R)-4-methyl-5-valerolactone 74 in nine steps (Scheme 8.6a). After convenient synthesis of aldehyde 77 and its asymmetric aldol condensation with the ketene acetal 79, HTMMD skeleton 80 was isolated as a single isomer. After installation of allyl ester, the alcohol was coupled with Fmoc-Ala-Cl in the presence of DMAP/DIPEA (4-dimethylaminopyridine/diisopropylethylamine) followed by fluorenylmethyloxy-carbonyl (Fmoc) deprotection to afford the ester segment 81b in excellent yield. The amount of DMAP and temperature (—15 °C) were critical to avoid racemiza-tion. Modified Tsunoda s diastereoselective aza-Claisen rearrangement [145] was used as the key step in the 13-step synthesis of N-methylhydroxyisoleucine 86b... 

---