Efficient Cycloisomerization of Propargyl Amides by Electrophilic Gold(I) Complexes of KITPHOS Monophosphines: A Comparative Study

Abstract

Electrophilic gold(I) complexes of diphenyl-and dicyclohexylphosphino-based KITPHOS monophosphines catalyze the 5-exo-dig cycloisomerization of a range of propargyl amides to afford the corresponding alkylidene oxazolines; in all cases catalysts formed from diphenylphosphino-substituted KITPHOS monophosphines outperformed their dicyclohexylphosphino counterparts as well as that based on triphenylphosphine, an indication that the biaryl/biaryl-like framework may be responsible for imparting high catalyst efficiency.

Gold‐Catalyzed Cyclizations: A Comparative Study of ortho,ortho′‐Substituted KITPHOS Monophosphines with their Biaryl Monophosphine Counterpart SPHOS

“…Under these conditions, although the yields were moderate to good they were consistently lower than those obtained with substrate 16. Interestingly, the yields did not improve when the catalyst loading was further increased to 0.25 mol%, rather, the yields were marginally lower for each catalyst and the TONs dropped from 660-730 to 232-272 (entries [10][11][12][13]. Again these values are quite similar to the values obtained with 12c (entry 14).…”

“…[11] The P(1) À Au(1) À S(3) angle of 174.38 (7)8 is close to linear and the Au(1) À P(1) and Au(1) À S(3) bond lengths of 2.2691 (18) and 2.327(2) , respectively, are similar to those in [(PPh 3 …”

“…[10a,11] Figure 4 also reveals that the proximal aryl ring is orientated parallel and close to the Au À P bond such that there is a weak h 1 -interaction between the gold atom and the ipso carbon atom of the aryl ring; the Au···C ipso distances of 3.187 (12a), 3.176(7) (12b) and 3.133 (7) (14) are less than the sum of the van der Waals radii and similar to the Au···C ipso interactions reported for gold(I) complexes of PCy 2 (o-biphenyl) [16c] and 11-(dicyclohexylphosphino)-12-(2-methoxyphenyl)-9,10-dihydro-9,10-ethenoanthracene. [11] With the intention of evaluating and comparing the efficiency of gold(I) tetrahydrothiophene complexes of KITPHOS monophosphines as precatalysts, 15a and 15b were also prepared by treatment of a dichloromethane solution of (tht)AuCl and the corresponding KITPHOS monophosphine with AgNTf 2 at room temperature (Scheme 3); the identify and purity of both complexes have been established using conventional spectroscopic and analytical techniques.…”

“…[11] Having already demonstrated that unsubstituted and monosubstituted KITPHOS monophosphines are efficient ligands for gold(I)-catalyzed cycloisomerizations, [11] we chose the same transformations to investigate the effect on catalyst performance of introducing ortho,ortho'-substituents on to the proximal aryl ring Scheme 2. Synthesis of KITPHOS gold(I) triflimide complexes 12a and 12b.…”

“…[10] While electrophilic Lewis acid gold(I) triflimide complexes of electron-rich KITPHOS monophosphines were shown to be an efficient catalyst for a range of cycloisomerizations to afford phenols, tetrahydropyrans, lactones and alkylidene-oxazolines, more recent studies have shown that catalysts based on diphenylphosphino-substituted KITPHOS monophosphines outperformed their electron-rich dicyclohexylphosphino counterparts for the cycloisomerization of a range of propargylic amides. [11] We have now undertaken a systematic comparison between the performance of ortho,ortho'-substituted KITPHOS monophosphines ( Figure 2) and their biaryl counterpart SPHOS in gold(I)-catalyzed cyclo-A C H T U N G T R E N N U N G isomerizations and herein disclose the details of this study which has shown that ortho,ortho'-MeO and Me-substituted KITPHOS monophosphines form efficient catalysts for a host of intramolecular cyclizations and that both compete with their SPHOS counterpart across a range of substrates.…”