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DOI: 10.1055/s-2006-949255
N-Acylsulfonamide Linker Activation by Pd-Catalyzed Allylation
Y. He, J. P. Wilkins, L. L. Kiessling*
University of Wisconsin-Madison, Madison, USA
Publication History
Publication Date:
23 August 2006 (online)
Significance
A new method for N-acylsulfonamide activation by palladium-catalyzed allylation was developed. Thus, the resin-supported peptides 2 and 3 were readily prepared from Gly, Ala, Leu, Ile, Phe, Ser, Lys, and His on the commercially available arylsulfonamide resin 1 (loading 0.62 mmol/g) by the standard Fmoc method using HATU and DIPEA as coupling reagents. Palladium-catalyzed allylations of N-acylsulfonamide resins 2 and 3 were carried out with allyl ethyl carbonate, Pd(OAc)2 and PPh3 to give the allylated substrates 2a and 3a, where the sulfonamide unit was activated as a leaving group. The reactions of activated resins 2a and 3a with n-PrNH2 released N-Boc-protected peptides were deprotected with TFA to give the peptides 4 and 5 with good crude purity and in good yield (54% and 40% yield from 1). Peptide thioesters 6 and 7 were also obtained via similar solid-phase transformations using ethyl 3-mercaptopropionate in 52% and 41% yields, respectively.