Copper-catalyzed O-arylation of N-protected 1,2-aminoalcohols using functionalized trivalent organobismuth reagents

Abstract

The O-arylation of 1,2-aminoalcohols using functionalized triarylbismuth reagents is reported. The reaction can be performed using substoichiometric amounts of copper acetate and operates under mild conditions. Good functional group tolerance is observed, giving access to a range of β-aryloxyamines. The effect provided by the amino group in the arylation reaction is investigated.

Copper‐Promoted O‐Arylation of the Phenol Side Chain of Tyrosine Using Triarylbismuthines

“…Recently, there has been a surge of interest for the chemistry of bismuth as demonstrated by the elegant work of Ball where a universal bismacycle was used in conjunction with meta ‐chloro peroxybenzoic acid to ortho ‐arylate an impressive range of phenols via a concerted mechanism (Scheme c ) . Over the past decade, our group has reported a repertoire of metal‐catalyzed reactions that involve trivalent organobismuth reagents and that result in the transfer of alkyl, cyclopropyl and aryl/heteroaryl groups onto various scaffolds. In 2014, we disclosed a highly efficient protocol for the O‐arylation of phenols using triarylbismuth reagents and hypothesized that the reaction proceeds through a copper(III) species where the metal center is simultaneously bound to the phenoxide and the aryl group (Scheme d ) .…”

“…Results show that N ‐Boc tryptophan methyl ester is as reactive as N ‐Boc tyrosine methyl ester and that N ‐Boc cysteine and histidine methyl esters are the third and fourth most reactive amino acids ( 3a , 4 – 6 ). The high reactivity of N‐protected tryptophan, cysteine and histidine is easily explained by the fact that triarylbismuthines are very efficient at arylating indoles,[12b] thiols and imidazoles N‐Protected serine, lysine and glutamine were much less reactive under these conditions ( 7 – 9 ). These results are somewhat surprising since 1,2‐amino alcohols,[12c] amines and amides can all be arylated efficiently with triarylbismuthines.…”

“…The high reactivity of N‐protected tryptophan, cysteine and histidine is easily explained by the fact that triarylbismuthines are very efficient at arylating indoles,[12b] thiols and imidazoles N‐Protected serine, lysine and glutamine were much less reactive under these conditions ( 7 – 9 ). These results are somewhat surprising since 1,2‐amino alcohols,[12c] amines and amides can all be arylated efficiently with triarylbismuthines. Therefore, they suggest that the reactivity of these particular functional groups is impacted by the presence of the ester and carbamate moieties.…”

Organobismuth Reagents: Synthesis, Properties and Applications in Organic Synthesis

“…In the course of our studies on the Narylation of indoles and other N-H-containing heterocycles, we found that 3-(3-hydroxypropyl)-1H-indole could be chemoselectively N-arylated by tritolylbismuth in the presence of copper acetate, leaving the primary alcohol intact (Scheme 24 A). 197 However, when the same conditions were applied to N-Boc-tryptophanol, a product of double arylation was obtained, showing that the NHBoc group activates the alcohol (Scheme 24 B). We then used this observation to O-arylate various amino alcohols (Scheme 24 C), demonstrating that diversely substituted aryl groups could be installed on the alcohol of N-Boc-phenylglycinol in moderate to good yields.…”

Synthetic Studies on Presporolide, a Putative Enediyne Precursor of Sporolides

“…Thus, treatment of tertiary alcohol 7 with 0.5 equiv of triarylbismuth 8 and 1.0 equiv of Cu­(OAc) 2 at room temperature furnished aryl ether 9 in 76% yield. It is noteworthy that employment of a stoichiometric amount of copper acetate under an oxygen atmosphere enabled us to use a trivalent arylbismuth as an aryl group donor rather than an unstable pentavalent arylbismuth. , After removal of the TES group, the resultant phenol 10 was attached to the two-carbon unit at C3′ through a regioselective formylation, Wittig olefination, followed by methylation of the phenol, to afford 11 . Installation of the C12–C13 alkyne group was achieved in a stereoselective manner using the following sequence.…”