3- crotonic esters, reaction with

Other approaches to (36) make use of (37, R = CH ) and reaction with a tributylstannyl allene (60) or 3-siloxypentadiene (61). A chemicoen2ymatic synthesis for both thienamycia (2) and 1 -methyl analogues starts from the chiral monoester (38), derived by enzymatic hydrolysis of the dimethyl ester, and proceeding by way of the P-lactam (39, R = H or CH ) (62,63). (3)-Methyl-3-hydroxy-2-methylpropanoate [80657-57-4] (40), C H qO, has also been used as starting material for (36) (64), whereas 1,3-dipolar cycloaddition of a chiral nitrone with a crotonate ester affords the oxa2ohdine (41) which again can be converted to a suitable P-lactam precursor (65). 

Based on our previous results on the nucleophilic alkenoylation of aldehydes via metallated a, 3-unsaturated aminonitriles [50], we now envisaged an enanti-oselective variant. Thus, the enantiopure a-aminonitriles 60 were metallated with LDA and by reaction with aldehydes the adducts 61 could be obtained. Subsequent cleavage of the aminonitrile function with silver nitrate led to the desired a -hydroxyenones 62 in overall yields of 29-80% and enantiomeric excesses ee of 50-69%. Alternatively, the conjugate addition of the lithiated aminonitrile 63 to t-butyl crotonate led to the y-keto ester 63 in 35% yield and an enantiomeric excess ee of >90% (Scheme 1.1.18). 

In the first reports on the use of esters of 4-bromo-2-butenoic acid (191a and b, crotonic acid) and of 4-bromo-3-methyl-2-butenoic acid (191c, senecioic acid), the corresponding Reformatsky reactions with benzaldehyde were performed with the old-fashioned procedure, which required heating the haloester, the aldehyde and granulated zinc in benzene/ether mixtures at reflux temperature. 

Amino-1,2,4-triazolo[l,5-a]pyrimidine derivatives (115) were prepared from 3,5-dihalo-l,2,4-triazoles (111) by amination followed by reaction with acrylic or crotonic ester (113) and then amination without the isolation of 112 and 114 [87T2497 88JAP(K)63/267782] (Scheme 22). 

Bestmann and Seng (5) reported that the reaction of methylene triphenylphosphorane with crotonic ester gave a cyclopropane derivative. We found that the less active carbomethoxymethylene triphenylphosphorane did not react with crotonic ester at all. 

When crotonate esters were employed the regioisomers 501 were mainly formed, accompanied by a significant amount of non-cyclic compounds 502 formally arising from insertion of the Si=C group in an ally lie C—H bond (equation 167). The reaction of silenes 149 and 150 with crotonate esters are the only examples known so far where the product distribution is different when the reaction is conducted under photolytic conditions or in the absence of light. Thus, in the dark reaction of 150 with methyl crotonate the relative ratio 501 (R1 = 1-Ad, R2 = Me) 502 (R1 = 1-Ad, R2 = Me) = 3.75 1 was obtained, while under photolytic conditions only minor amounts of 501 were detected245. The nominal insertion product 503 is also the major product in the reaction of methacrylate esters with 149 and 150 (equation 168). The minor product in this reaction is the l-sila-3-oxacyclohex-4-ene 504 (relative ratio 503 504 = 5.7 l)245. 

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. 

It has been demonstrated that optically active oxetanes can be formed from oxazolidinone 92, a crotonic acid moiety functionalized with Evans chiral auxiliary (Scheme 18) <1997JOC5048>. In this two-step aldol-cyclization sequence, the use of 92 in a deconjugative aldol reaction, with boron enolates and ethanal, led to formation of the syn-aldol 93. This product was then converted to the corresponding oxetanes, 94a and 94b, via a cyclization with iodine and sodium hydrogencarbonate. This reaction sequence was explored with other aldehydes to yield optically active oxetanes in similar yields. Unlike previous experiments using the methyl ester of crotonic acid, in an analogous reaction sequence rather than the oxazolidinone, there was no competing THF formation. 

Simple diastereoselectivity may also occur in Diels-Alder reactions between electron-poor dienophiles and cyclopentadiene (Figure 15.30). Acrylic acid esters or fraus-crotonic acid esters react with cyclopentadiene in the presence or absence of A1C13 with substantial selectivity to afford the so-called emfo-adducts. When the bicyclic skeleton of the main product is viewed as a roof the prefix endo indicates that the ester group is below this roof, rather than outside (exo). However, methacrylic acid esters add to cyclopentadiene without any exo.endo-selectivity regardless whether the reaction is carried out with or without added A1C13 (Figure 15.30, bottom). 

Vitamin A acid, especially used in the treatment of acne for some years, can also be obtained by Wittig reaction. Thus, olefination of phosphorane 506, with y-formyl-crotonic ester 509 as well as the reversed Wittig olefination, i.e. the conversion of aldehyde 511 and ylide 512 yields the ester 510 of vitamin A acid 255), according to Scheme 86. 

Fig. 9.3. The pair of reactions illustrates the occurrence of stereoselectivity and the lack of stereospecificity in two cyclopropanations with an S ylide. The trans-crotonic acid methyl ester reacts with complete retention of the configuration, whereas the di-crotonic acid methyl ester reacts with complete inversion.

In agreement with frontier orbital considerations, crotonic esters add to nitrones to produce p-o o esters regioselectively. This reaction provides the basis for a synthesis of the Senecio alkaloid supinidine (7). Reaction of 1 with methyl 4-hydroxycrotonate yields the isoxazolidinone 5, which is easily converted to the... 

Some of the Lewis acid catalyzed Michael additions to a,3-unsaturated carbonyls can also be rationalized based on these models. For example, BFs-mediated additions of organocopper reagents to chiral a,3-unsaturated esters such as (-)-8-phenylmenthyl crotonate (35) occur with high levels of dia-stereoselectivity. " The product stereochemistries for these reactions could be predicted by assuming the reactive conformation (35S), which follows the basic structural tenets of model A (Figure 41). ... 

Aminoalkylation. The use of (ArO)2Ba in THF to deprotonate 3-butenoic esters for reaction with A -phosphinylaldimines gives a-substituted crotonates. 

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