Preparation of Enamides via Palladium-Catalyzed Amidation of Enol Tosylates

Abstract

[reaction: see text] A Pd-catalyzed coupling of enol tosylates and amides has been developed. Ligand screening revealed dipf as the most general ligand for this transformation. A variety of enol tosylates were coupled to an array of enamides in 58-97% yield.

Biaryl Phosphane Ligands in Palladium‐Catalyzed Amination

“…[134] Chemists at Merck have shown that to couple vinyl triflates [135] and vinyl tosylates [136] with an activating substituent at the β position with amides the best systems are provided by the chelating ligands Xantphos and dipf (1,1′-bis(di-iso-propylphosphino)ferrocene) respectively. When Willis came to examine the coupling of unactivated vinyl triflates and tosylates, however, ligand 6 proved to be optimal (Scheme 4).…”

Synthesis of 1,2‐Amino Alcohols by Sigmatropic Rearrangements of 3‐(N‐Tosylamino)allylic Alcohol Derivatives

“…Deprotection of the alcohol (TBAF, THF) led to ynamide 6, which underwent stereoselective hydroalumination with Red-Al to provide the (E)-3-(N-tosylamino)allylic alcohol 3 a (68 %, two steps from 5). Alternatively, ynamide 5 was treated with an excess of the titanium reagent [h 2 -(propene)]TiA C H T U N G T R E N N U N G (OiPr) 2 , [6h,i] followed by hydrolysis to provide enamide 7 and subsequent cleavage of the silyl ether (TBAF) afforded the isomeric Z allylic alcohol 3' a (59 %, two steps from 5) (Scheme 3).…”

“…The low and abnormal diastereoselectivity observed in the Ireland-Claisen rearrangement of glycolate 22 led us to explore the alternative route towards 1,2-amino alcohols E relying on the use of a [2,3]-Wittig rearrangement.…”

“…Unlike in the Ireland-Claisen rearrangement, the presence of the N-tosylamino substituent had no adverse effect on the 1,2-diastereoselectivity of the Wittig rearrangement. [41] The other a-allyloxy amides 27 b-f derived from primary (E)-3-(N-tosylamino)allylic alcohols were found to undergo a diastereoselective [2,3]-Wittig rearrangement (diastereomeric ratio (d.r.) = 90:10 to > 96:4) under the previously optimized conditions.…”

“…Whereas the presence of the nitrogen atom alters the stereochemical outcome of Ireland-Claisen rearrangements of glycolates derived from such substrates, [2,3]-Wittig rearrangements stable to a wide variety of reaction conditions and to avoid the presence of rotamers in equilibrium, a key issue to consider as the stereochemical outcome (1,2-diastereoselectivity) of the sigmatropic rearrangements will have to be evaluated. While N-alkenyl-oxazolidin-2-ones have typically been employed as enamides, [1][2][3][4][5][6][7] embedding the nitrogen atom into an oxazolidinone ring excludes the possibility of having a variety of substituents on the latter atom, which could be potentially useful for further functionalization.…”