Ethyl crotonate, reactions

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%. 

Palladium(II) acetate was found to be a good catalyst for such cyclopropanations with ethyl diazoacetate (Scheme 19) by analogy with the same transformation using diazomethane (see Sect. 2.1). The best yields were obtained with monosubstituted alkenes such as acrylic esters and methyl vinyl ketone (64-85 %), whereas they dropped to 10-30% for a,p-unsaturated carbonyl compounds bearing alkyl groups in a- or p-position such as ethyl crotonate, isophorone and methyl methacrylate 141). In none of these reactions was formation of carbene dimers observed. 7>ms-benzalaceto-phenone was cyclopropanated stereospecifically in about 50% yield PdCl2 and palladium(II) acetylacetonate were less efficient catalysts 34 >. Diazoketones may be used instead of diazoesters, as the cyclopropanation of acrylonitrile by diazoacenaph-thenone/Pd(OAc)2 (75 % yield) shows142). 

The Michael-type reaction of an anion (generated from compound 77) with ethyl crotonate yielded the corresponding ester 78 in 82% yield (Scheme 19). Alkylation of compound 77 with benzyl bromide afforded derivative 79 in 85% yield. The attempted reactions of the anion with oxiranes and trimethylsilyl chloride did not lead to the expected substitution products and the starting oxadiazoles were recovered in 70-80% yields <2001ARK101>. 

The preparation of the oily ethyl 2,3-diphenyl-5-methyl-isoxazolidine-4-carboxylate provides another example of this reaction. As in the procedure described with styrene, 10.0 g. (50.7 mmoles) of N,a-diphenylnitrone is heated under nitrogen for 24 hours at 90-100° with 35.0 g. (38.0 ml., 307 mmoles) of ethyl crotonate. The excess olefin, b.p. 45° (12 mm.) is removed on the water pump, and the red-orange residue, while still warm, is transferred to a 50-ml. Claisen flask using acetone as a rinse. 

The 3-methyl derivative of (142 R = H) was prepared by Krishnan210 from 2-aminopyridine and methyl methacrylate or methyl 3-bromoiso-butyrate. These reagents, however, were not able to transform the methyl derivatives of 2-aminopyridine to pyrido[l,2-a]pyrimidines.209 Reaction of 2-aminopyridine with ethyl 3-bromobutyrate and ethyl crotonate also was not successful. 

The stereochemistry of conjugate additions requires similar considerations to those used to predict nucleophilic attack on a carbonyl. Acyclic substrates may yield up to three contiguous chiral centres (Scheme 18). The relative stereochemistry of carbons C(l) and C(2) will depend upon the approach of the two reagents. The stereochemistry of carbon C(3) will depend upon the lifetime of the intermediate 30 if it has even a short lifetime it will take up the most stable conformation. For example, the base-catalysed additions of ethanol-d and 2-methyl-2-propanethiol-d to ethyl crotonate give a (2R, 3R )/(2R, 3S ) diastereoisomeric ratio of the addition products of approximately 10 190. The authors90 suggest the reaction proceeds in two steps and the protonation of the enolate determines the stereoselectivity. 

The use of dimethylsulphoxonium methylide, as a specific methylene insertion reagent for a, /J-unsaturated ketones and esters, is illustrated by its reaction with ethyl crotonate in dimethylformamide solution to form (39) (Expt 7.16).12 The sulphur ylide initially attacks the /J-carbon of the conjugated system (Michael acceptor site), and this is followed by cyclisation and loss of dimethyl sulphoxide. 

To a suspension of sodium hydride (1.2g, 0.05 mol) in dimethylformamide (100 ml) is added in one portion solid trimethylsulphoxonium iodide (11.05 g, 0.052 mol) (1). An exothermic reaction takes place with copious evolution of hydrogen. After all the hydrogen has been evolved (5 minutes), the mixture is stirred for another 15 minutes, and ethyl crotonate (5.7 g, 0.05 mol) in dimethylformamide (15 ml) is added to the methylide in one portion. An exothermic reaction takes place and the mixture turns slightly yellow. Stirring is continued for another hour. The mixture is poured into hydrochloric acid-ice-water (100 ml, 3%), extracted with ether (3 x 50 ml), the ether extract... 

The reactions of ethyl acrylate and ethyl crotonate were studied (117) in the presence of ethyl orthoformate using 1 1 CO/H2 and 250 and 200 atm pressure. For ethyl acrylate, the distribution of products corresponded to j3-hydroformylation 78.2%, (y,y-diethoxybutyrate and j3-formylpropionic acid), and a-hydroformylation 21.7%, (a-methyl-j8-ethoxyacrylate and -methyl-j3,/3-diethoxypropionate). For ethyl crotonate, y-hydroformyla-tion occurred to the extent of 67-73% (8,8-diethoxyvalerate and y-formyl-butyrate) and a-hydroformylation to the extent of only 13.6% (a-ethyl-/ -ethoxyacrylate and j3-ethyl-j8-diethoxypropionate). 

Aliphatic a,/3-unsaturated esters undergo the hydroformylation reaction. Ethyl acrylate, ethyl crotonate, and diethyl fumarate react as shown in Equations 1, 2, and 3, respectively. 

Addition of carbon monoxide and hydrogen to an alkene linkage in the presence of cobalt catalysts gives aldehydes in an average yield of 50%. The reactions may be carried out in the usual hydrogenation apparatus. The poisonous properties of carbon monoxide and cobalt carbonyls call for considerable care. Compounds made by hydroformylation include cyclopentanealdehyde from cyclopentene (65%), /3-carbethoxy-propionaldehyde from ethyl acrylate (74%), and ethyl /3-formylbutyrate from ethyl crotonate (71%). 

Facile reaction of electron-deficient olefins (dipolarophiles) such as rra/i5-dibenzoylethylene, dimethyl fumarate, furanonitrile, methyl vinyl ketone, ethyl crotonate, ethyl acrylate, ethyl methacrylate, and dimethyl maleate with a mesoionic compound containing a masked thiocarbonyl ylide skeleton gives stable 1 1 cycloadducts. The structure of the cycloadduct was established by its carbonyl absorption in IR spectra and the molecular ion peak [M]. The stereochemistry of the cycloadducts was, however, secured by NMR spectra (74JOC3631) (Scheme 100). 

There have been only a limited number of developments in this area, the majority of which involve the use of lithium diisopropylamide (LDA) with chiral l,3-dioxolan-4-ones to deprotonate the C-5 position and allow reaction with a suitable electrophile (Equation 21). Electrophiles used to alkylate the enolate include iodomethane <1996HCA1696>, ethyl crotonate <1998SL102>, a,/ -unsaturated ketones <2006T9174>, various substituted nitrostyrenes <2004T165>, substituted nitroaryl fluorides <2003SL2325> and acylsilanes <2002TA1825>. 

Simple alkyl acrylates have been used as partner in mixed hydrocoupling reactions in a number of cases (Table 14). Like mixed couplings with 7, LHD formation and hydrogenation compete with formation of the MHC of alkyl acrylates. Coelectrolysis of ethyl 3,4-dimethoxycinnamate Ey z= —1.94 V) with ethyl crotonate Ey = —2.37 V) in a molar ratio of 1 7.2 in MeCN at E = —2.03 V gave none of the MHC bW only the CHD of the cinnamate. The only product derived from the crotonate was diethyl 2-ethylidene-3-methylglutarate (49%) formed by action of an EGB, most likely the dimer dianion of the cinnamate [61]. 

Recent developments include an asymmetric version of the aldol reaction in the y-position. The silyl enol ether 82 from ethyl crotonate reacts with aldehydes in the presence of the Lewis acid SiCI4 and an asymmetric catalyst (see the paper if you are interested in the structure of this complex catalyst) to give a high yield of the aldol product 83. The y a ratio is >99 1 and the product 83 is virtually enantiomerically pure.23... 

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