Stereo- and Regioselective Gold-Catalyzed Hydroamination of Internal Alkynes with Dialkylamines

Abstract

We report the use of a P,N-ligand to support a gold complex as a state-of-the-art precatalyst for the stereoselective hydroamination of internal aryl alkynes with dialkylamines to afford E-enamine products. Substrates featuring a diverse range of functional groups on both the amine (ether, sulfide, N-Boc amine, fluoro, nitrile, nitro, alcohol, N-heterocycles, amide, ester, and carboxylic acid) and alkyne (ether, N-heterocycles, N-phthalimide amines, and silyl ethers) are accommodated with synthetically useful regioselectivity.

Preparation and characterization of the ‘research chemical’ diphenidine, its pyrrolidine analogue, and their 2,2‐diphenylethyl isomers

“…The 1 H and 13 C spectra of (3) free base were consistent with data published previously. [31] For convenience the 1 H and 13 C assignments for the assigned aliphatic shifts for compounds (1) -(4) and the HCl salt of (1) (1) and (3) were observed further downfield when compared to their 2,2-diphenylethylamine isomers (2) and (4) due to the electron-withdrawing effect of the phenyl substituent at C 1 . This ∆C 1 was 5.6−11.6 ppm.…”

“…The implementation of ESI-MS/MS did not reveal differential fragmentations between isomers (1)/(2) and (3)/(4) as observed under EI and CI conditions (Figure 3). However, a difference in relative abundance observed 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 The 1 H and 13 C spectra of (1), (R)- (1) and (S)- (1) free base and the hydrochloride salt have been previously published [14,31] and the results obtained in the present study were largely consistent. Two "additional" 13 C chemical shifts were reported with the hydrochloride salt.…”

“…[21] A number of additional synthetic routes to diphenidine have been described and include modified Mannich-type reactions employing benzyl bromide, piperidine and benzaldehyde [30] and gold-catalyzed hydroamination of diphenylacetylene with piperidine. [31] ((Please insert Figure 2 about here))…”

Silver-free Gold(I) Catalysts for Organic Transformations

“…The former two components provide the complex [(NHC)AuCl] which then is activated by the tetrakis(pentafluorophenyl)borate salt. Diphenylacetylene and morpholine undergo a cisaddition to yield the corresponding morpholino-alkene and -after reduction -the corresponding alkanes (Scheme 23) [76].…”

Synthesis of N-heterocycles through cyclization-triggered tandem additions to alkynes and the study of promoters in ionic reactions.

“…Again, KCTf3 accelerated significantly and consistently all the gold catalyzed reactions tested. For example, in X-H (X = O, N) additions to alkyne/alkene (Scheme 15, a-b), [70][71][72][73][74][75][76][77][78][79][80] KCTf3 increased the reaction rate 3.5 and 11 fold. In the cycloisomerization of 1,6-enynes (Scheme 15, c-d) [81][82][83] KCTf3 increased the reaction rate up to 33 fold.…”