Mild and Regioselective Pd(OAc)2-Catalyzed C–H Arylation of Tryptophans by [ArN2]X, Promoted by Tosic Acid

TY - JOUR

T1 - Mild and Regioselective Pd(OAc)2-Catalyzed C–H Arylation of Tryptophans by [ArN2]X, Promoted by Tosic Acid

AU - Reay, Alan James

AU - Hammarback, Lars Anders

AU - Bray, Joshua Thomas William

AU - Sheridan, Thomas

AU - Turnbull, David

AU - Whitwood, Adrian C.

AU - Fairlamb, Ian James Stewart

N1 - © 2017. The Author(s).

PY - 2017/8/4

Y1 - 2017/8/4

N2 - A regioselective Pd-mediated C–H bond arylation methodology for tryptophans, utilizing stable aryldiazonium salts, affords C2-arylated tryptophan derivatives, in several cases quantitatively. The reactions proceed under air, without base and at room temperature in EtOAc. The synthetic methodology has been evaluated and compared against other tryptophan derivative arylation methods using the CHEM21 Green Chemistry Toolkit. The behavior of the Pd catalyst species has been probed in preliminary mechanistic studies, which indicates that the reaction is operating homogeneously, although Pd nanoparticles are formed during substrate turnover. The impact of these higher order Pd species on catalysis, under the reaction conditions examined, appear to be minimal, e.g. acting as a Pd reservoir in the latter stages of substrate turnover or as a moribund-form (derived from catalyst deactivation). We have determined that TsOH shortens the induction period observed when employing [ArN2]BF4 salts with Pd(OAc)2. Pd(OTs)2(MeCN)2 was found to be a superior precatalyst (confirmed by kinetic studies) to Pd(OAc)2.

AB - A regioselective Pd-mediated C–H bond arylation methodology for tryptophans, utilizing stable aryldiazonium salts, affords C2-arylated tryptophan derivatives, in several cases quantitatively. The reactions proceed under air, without base and at room temperature in EtOAc. The synthetic methodology has been evaluated and compared against other tryptophan derivative arylation methods using the CHEM21 Green Chemistry Toolkit. The behavior of the Pd catalyst species has been probed in preliminary mechanistic studies, which indicates that the reaction is operating homogeneously, although Pd nanoparticles are formed during substrate turnover. The impact of these higher order Pd species on catalysis, under the reaction conditions examined, appear to be minimal, e.g. acting as a Pd reservoir in the latter stages of substrate turnover or as a moribund-form (derived from catalyst deactivation). We have determined that TsOH shortens the induction period observed when employing [ArN2]BF4 salts with Pd(OAc)2. Pd(OTs)2(MeCN)2 was found to be a superior precatalyst (confirmed by kinetic studies) to Pd(OAc)2.

KW - aryldiazonium salt

KW - chirality

KW - cross-coupling

KW - directing group

KW - heteroarene

KW - palladium

KW - regioselectivity

UR - http://www.scopus.com/inward/record.url?scp=85027243858&partnerID=8YFLogxK

U2 - 10.1021/acscatal.6b03121

DO - 10.1021/acscatal.6b03121

M3 - Article

SN - 2155-5435

VL - 7

SP - 5174

EP - 5179

JO - ACS Catalysis

JF - ACS Catalysis

IS - 8

ER -