Synthesis of (Z)‐β‐(Carbonylamino)alkenylindium through Regioselective anti‐Carboindation of Ynamides and Its Transformation to Multisubstituted Enamides

Abstract

The regioselective anti-carboindation of ynamides by usingI nBr 3 and silylated nucleophilesw as developed to synthesize (Z)-b-(carbonylamino)alkenylindiums. The X-ray crystallographic analysis of an alkenylindium suggested that the reaction proceeded in an anti-addition fashion.I nc ontrastt or eported syn-carbometalationso f ynamides by using organometallics, ac ooperation of InBr 3 and silylated nucleophiles to ynamides achieveda nantiaddition, whichw as supportedb yD FT calculations. The scope of substrates included variousy namides and silylated nucleophiles, such as silyl ketenea cetals and silyl ketene imines. The transformation of synthesized alkenylindiumsb yi odination,r adicalc oupling, and Pd-catalyzed cross-couplings uccessfully afforded trisubstituted enamines with high regio-and stereoselectivities.Enamides are versatile buildingb locks for valuable nitrogencontaining compounds. [1] Ac ombinationo fc arbometalations of ynamides and transformations of the formed metalated enamides is one of the most reliable synthetic methods for multisubstituted enamides. [2] In this strategy,e stablishmento fr egioand stereoselective carbometalation is necessary for selectively synthesizing ad esired enamide among possiblei somers. Syncarbometalation of ynamides of organometallic compounds has been widely studied (Scheme1a). For example, a-(carbonylamino)alkenylmetals are obtained through the syn-addition of organocoppers, -zincs,a nd -lithiums to ynamides. [3,4] In contrast, b-(carbonylamino)alkenylmetalsa re obtained by syn-carbopalladation of ynamides by using organopalladiums. [5] How-ever, anti-carbometalation of ynamides remains underdeveloped,a lthough the intramolecular carbometalations of ynamidesh ave been reported (Scheme 1b). [6] We recently reported intermolecular anti-carbometalations of carbon-carbon triple bonds by using silylatedn ucleophiles and metal salts, such as InBr 3 ,G aBr 3 ,A lBr 3 ,B iBr 3 ,a nd ZnBr 2 . [7] Therefore, we assumedo ur strategy could achieve anti-carbometalation of ynamides. Here, we report the anti-carbometalation of ynamides by using InBr 3 and silyl ketene acetals to synthesize (Z)-b-(carbonylamino)alkenylindiums(Scheme 1c).First, we surveyed metal halides fort he carbometalation of N-ethynylpyrrolidone (1a)b yu sing the silyl ketene acetal 2a (Table 1). The reactiono fy namide 1a by using InBr 3 and 2a followed by the addition of MeOH exclusively gave the product 3aa in 96 %y ield, where the carbon-carbon bond was formed at the carbon atom adjacent to the nitrogen atom (Table 1, entry 1). This results howed that enamide 3aa was produced by the protonationo fb-(carbonylamino)alkenylindium (detailsa re described below). Notably,r egioisomers obtainedf rom a-(carbonylamino)alkenylindiumsw ere not found despite the existenceo fa na mide moiety,w hich often serves Scheme1.Carbometalation of ynamides. Entry YnamideProduct [b] Entry YnamideP roduct [b] 1 4 2 5 3 6[a] InBr 3 (0.5 mmol), 1 (0.5 mmol), 2a (1.5 mmol), CH 2 Cl 2 (1 mL), I 2 (1.5 mmol), and DMF (1.5 mL).[b] Y...

Regioselective Carbozincation and Further Functionalization of Allenamides Catalyzed by an N‐Heterocyclic Carbene (NHC)‐Copper Complex

“…Recently, carbometalation of ynamides [6][7][8][9][10][11] has attracted much attentions as a straightforward approach for the regioand stereo-selective synthesis of multi-substituted enamides (Scheme 1a). In general, the carbometalation of ynamides proceeds regioselectively, introducing the metal unit to the proximal carbon with the help of the coordination of the amide moiety (N-EWG).…”