Coupling methyl 3- acrylate

The combination of ethanol/water/DME and N-methyl-2-pyrrolidone (NMP) was found to interact sufficiently strongly with microwave and generates the heat required to promote the Stille cross-couplings. Methyl acrylate was converted smoothly to the corresponding cinnamic acid esters in 3.8 min at 60 W in the presence of DMF (Patel et al., 1977). 

If chain transfer of the radical center to a previously formed polymer molecule is followed ultimately by termination through coupling with another similarly transferred center, the net result of these two processes is the combination of a pair of previously independent polymer molecules. T. G. Fox (private communication of results as yet unpublished) has suggested this mechanism as one which may give rise to network structures in the polymerization of monovinyl compounds. His preliminary analysis of kinetic data indicates that proliferous polymerization of methyl acrylate may be triggered by networks thus generated. 

Palladium metal catalysts supported on organic resins containing tertiary amino, cyano, carboxyl, and pyridyl groups have been recently investigated in some Heck reactions, such as the coupling of iodobenzene with methyl acrylate and methyl vinyl ether (Scheme 11) [31]. 

In 2000, Morken et al. reported the first examples of catalytic asymmetric reductive aldol reactions [21]. Using Rh(BINAP) (5mol%) as catalyst and Et2MeSiH as reductant, the syn-selective (1.7 1) coupling of benzalde-hyde and methyl acrylate produced the diastereomers 35-syn and 35-anti in 91% ee and 88% ee, respectively. Using phenyl acrylate as the nucleophilic partner, a favorable yield of 72% was obtained for the aldol product 36 (Scheme 12). Several aldehydes were examined, which exhibit higher levels of syn-selectivity. Expanding the scope of substrates and acrylates under... 

Isayama described the coupling reaction of N-methylimine 157 and ethyl crotonate catalyzed by Co(acac)2 and mediated by PhSiH3 to produce Mannich product 158 in 82% with syn-selectivity (Scheme 41) [71]. The (i-laclam 159 was readily synthesized by heating 158. In 2002, Matsuda et al. reported cationic Rh complex [Rh(COD) P(OPh)3 2]OTf (1 mol%) as an active catalyst for the reductive Mannich reaction [72]. N-Tosylaldiminc 160 was coupled with methyl acrylate and Et2MeSiH (200 mol%) at 45 °C to give the b-amino ester 161 in 96% with moderate anti-selectivity 68%. 

Matsuda et al. applied aryl isocyanates as acceptors in reductive couplings to methyl acrylate (Scheme 44) [77]. The cationic Rh complex [Rh(COD) P(OPh)3 2]OTf (1 mol%) and Et2MeSiH (200 mol%) catalyze the reaction in refluxing CH2C12 to provide products of hydrocarbamoylation,... 

The 1,2-benzothiazepine 1,1-dioxides 126 were prepared in fair yields (e.g. 126, R = H, Ar = p-ClC6H4, 52%) by a Heck coupling on the precursors 125, which were obtained in turn from an aza Baylis-Hillman reaction involving the appropriate sulfonamide, aldehyde, and methyl acrylate reactants <06TL8591>. 

The reaction of //-protected dehydroalanine methyl esters (e.g. 56, 59) with other indoles 58 can also be effected to give the corresponding dehydrotryptophans 60, invariably as the Z-isomers [81]. Murakami, Yokoyama and co-workers also studied oxidative couplings of acrylates, acrylonitrile, and enones with 2-carboethoxyindole, 1-benzylindole, and l-benzyl-2-carboethoxyindole and PdCfe and CuCk or Cu(OAc) 2 to give C-3 substitution in 50-84% yields [82, 83]. 

In addition to examining the vinylation of l-methyl-2-indolecarboxaldehyde with methyl acrylate (Pd(OAc>2/HOAc/AgOAc) to give methyl ( )-3-(2-formyl-l-methyl-3-indoiyl)-acrylate in 60% yield, Pindur found that similar reactions of methyl 3-(l-methyl-2-indolyl)-acrylate afford bis(carbomethoxy)carbazoles albeit in low yield [85]. Fujiwara discovered that the combination of catalytic Pd(OAc)2 with benzoquinone and t-butylhydroperoxide serves to couple indole with methyl acrylate to give methyl ( )-3-(3-indolyl)acrylate in 52% yield [86]. 

Somei and co-workers made extensive use of the Heck reaction with haloindoles in their synthetic approaches to ergot and other alkaloids [26, 40, 41, 240-249]. Thus, 4-bromo-l-carbomethoxyindole (69%) [26], 7-iodoindole (91%) (but not 7-iodoindoline or l-acetyl-7-iodoindoline) [40, 41], and l-acetyl-5-iodoindoline (96%) [41] underwent coupling with methyl acrylate under standard conditions (PdlOAc /PhsP/EtjN/DMF/100 °C) to give the corresponding (E)-indolylacrylates in the yields indicated. The Heck coupling of methyl acrylate with thallated indoles and indolines is productive in some cases [41, 241, 246]. For example, reaction of (3-formylindol-4-yl)thallium bis-trifluoroacetate (186) affords acrylate 219 in excellent yield [241], Similarly, this one-pot thallation-palladation operation from 3-formylindole and methyl vinyl ketone was used to synthesize 4-(3-formylindol-4-yl)-3-buten-2-one (86% yield). 

The vinyl triflate of Komfeld s ketone has been subjected to Heck reactions with methyl acrylate, methyl methacrylate, and methyl 3-(Af-rerf-butoxycarbonyl-lV-methyl)amino-2-methylenepropionate leading to a formal synthesis of lysergic acid [259]. A similar Heck reaction between l-(phenylsulfonyl)indol-5-yl triflate and dehydroalanine methyl ester was described by this research group [260]. Chloropyrazines undergo Heck couplings with both indole and 1-tosylindole, and these reactions are discussed in the pyrazine Chapter [261], Rajeswaran and Srinivasan described an interesting arylation of bromomethyl indole 229 with arenes [262]. Subsequent desulfurization and hydrolysis furnishes 2-arylmethylindoles 230. Bis-indole 231 was also prepared in this study. 

In contrast to silylcarbenes, the analogous stannylcarbenes 2p are not stable, which explains why they have attracted little interest. Their instability is probably due to the long carbon-tin bond, which does not allow sufficient steric protection of the carbene center. Their reactivity seems to be quite similar to that of stable (phosphino)(silyl)carbenes Cyclopropanation reactions have been reported with methyl acrylate as well as coupling reactions with tert-butyl isonitrile.73... 

The 5-iodo derivative 1016 was prepared by reaction of the acetate of 999 with iodine monochloride, and subsequent deprotection using sodium methoxide in methanol. The protected derivative 1016 is a suitable precursor for use in cross-coupling reactions to prepare the unsaturated analogs 1018 and 1019. Thus, reaction of 1016 with methyl acrylate in the presence of palladium(II) acetate gave the ( )-5-(2-methoxycarbonylvinyl)uracil 1017 this was converted into the ( )-5-(2-bromovinyl) analog 1019 by alkaline... 

Examples are known of hydrocoupling between methyl acrylate and ketones in both protic and aprotic solvents. Reaction in acid solution is thought to involve reduction of the protonated ketoneto a radical, which adds to acrylate. In aprotic solvents, the ketone is more difficult to reduce and electron addition occurs on methyl acrylate. Modest yields of coupling product, dimethylbutanolide, are obtained from acetone and methyl acrylate in dimethylformamide [134]. Better results are obtained by reduction of methyl acrylate and an exces of the carbonyl compound in dimethyIformamide in the presence of chlorotrimethylsilane [135]. This process is useful for the synthesis of butenolides and some examples are given in Table 3.8. 

Kragl 13) pioneered the use of membranes to recycle dendritic catalysts. Initially, he used soluble polymeric catalysts in a CFMR for the enantioselective addition of Et2Zn to benzaldehyde. The ligand a,a-diphenyl-(L)-prolinol was coupled to a copolymer prepared from 2-hydroxyethyl methyl acrylate and octadecyl methyl acrylate (molecular weight 96,000 Da). The polymer was retained with a retention factor > 0.998 when a polyaramide ultrafiltration membrane (Hoechst Nadir UF PA20) was used. The enantioselectivity obtained with the polymer-supported catalyst was lower than that obtained with the monomeric ligand (80% ee vs 97% ee), but the activity of the catalyst was similar to that of the monomeric catalyst. This result is in contrast to observations with catalysts in which the ligand was coupled to an insoluble support, which led to a 20% reduction of the catalytic activity. 

Similarly, Uneyama and Watanabe (91TL1459) have reported the synthesis of trifluoromethylated AI-aryl-1-azabutadienes by palladium-catalyzed coupling of trifluoroacetimidoyl iodides with alkenes as well as the transformation of the azadiene derived from methyl acrylate into the corresponding 4-methoxycarbonyl-2-trifluoromethylquinoline in quantitative yield. 

The oxazolo[4,5-/> pyridinc system showed similar reactivity too. Its 6-bromo derivative underwent Heck coupling with methyl acrylate in DMF in... 

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