To unsaturated ester

The addition of diazomethane to unsaturated esters (1), as ethyl acrylate, methyl crotonate and ethyl cinnamate, was investigated by Auwers who showed that the primary addition product is a A -pyrazoline (2) which rearranges spontaneously to the conjugated A -pyrazoline (3). 

A reaction related to the Michael addition reactions of enamines to unsaturated esters, which leads to S-ketoesters, is the reaction with 1-carb-ethoxy-l-cyanocyclopropane (318). This gives access to ketones substituted with the next higher homologous acid chain. 

Only strong oxidants can react dangerously with saturated esters. Unsaturated esters have often been involved, but the reaction mainly concerns non-saturation the ester group can increase the risk by boosting the double bond reactivity. Therefore, reference to unsaturated esters will be concerned with this type of reaction. 

Recently, a thiazolium-catalyzed conjugate addition of acylsilanes to unsaturated esters and ketones was reported (Scheme 61).147... 

Conjugate addition to unsaturated esters.13 The mixed cuprate formed from butyllithium and copper(I) trimethylsilylacetylide, (CH3)3SiC=CCu, is more efficient than BuCu/BFj or Bu2CuLi for conjugate addition to a, p-unsaturated esters. Yields of the adduct are markedly improved by addition of CISi(CH3)3 (1.3 equiv.) to the reaction. 

Synthesis of a C(8)-C(18) segment of the larger fragment of lb using the same basic strategy is depicted in Scheme 25. Here, hydroxy ketone 176 was subjected to syn-selective (dr of crude product=90 10) reductive amination [42] with sodium cyanoborohydride and benzylamine followed by tetrahydro-oxazine formation using aqueous formaldehyde. The resulting heterocycle 182 was then converted to unsaturated ester 184 by successive desilylation, oxidation, and entirely (Z)-selective Horner-Wadsworth-Emmons olefination. Re-... 

Benzylic organomanganese reagents prepared by direct insertion of activated manganese metal display the same behavior (Scheme 2.60) [131]. Excellent results are also obtained for 1,4-additions of organomanganese reagents to unsaturated esters in the presence of CuCI (3 mol%) [127]. 

Esters of A -(phenylthiomethyl)AAs undergo a base (NaH)-promoted addition to unsaturated esters to give a mixture of diastereroisomeric regioi-somers (Scheme 9) (84TL1579). 

Fig. 10 Ishikawa s proposed pre-transition state for the Michael addition of glycines to unsaturated esters...

Enol Alkylcyanacetic Esters to Unsaturated Esters. J. Amer. chem. Soc. S3, 1150 (1931). 

Addition of organometallic compounds to unsaturated esters 5-20 Addition of tin and mercury hydrides to unsaturated ketones 5-22 Free-radical addition of carboxylic esters to olefins... 

Palladium (II) chloride alone in acetic acid oxidizes olefins to unsaturated esters. For instance ethylene is oxidized to vinyl acetate. Reaction 20 almost certainly proceeds by way of a Pd (II) a-bonded... 

A highly selective method for the preparation of optically active 3-substituted or 3, y-disubstituted-S-keto esters and related compounds is based on asymmetric Michael additions of chiral hydrazones (156), derived from (5)-l-amino-2-methoxymethylpyrrolidine (SAMP) or its enantiomer (RAMP), to unsaturated esters (154).167-172 Overall, a carbonyl compound (153) is converted to the Michael adduct (155) as outlined in Scheme 55. The actual asymmetric 1,4-addition of the lithiated hydrazone affords the adduct (157) with virtually complete diastereoselection in a variety of cases (Table 3). Some of the products were used for the synthesis of pheromones,169 others were converted to 8-lactones.170 The Michael acceptor (158) also reacts selectively with SAMP hydrazones.171 Tetrahydroquinolindiones of type (159) are prepared from cyclic 1,3-diketones via SAMP derivatives like (160), as indicated in Scheme 56.172... 

The catalytic dicarbonylation of ethylene to dimethyl succinate can be carried out in 90% conversion.94 High reaction temperatures and low carbon monoxide pressures can lead to unsaturated esters as a result of a faster -hydride elimination from the intermediate (23) than carbon monoxide insertion. This later reaction path has been termed oxidative carboxylation. 

The addition of lithium (.Sj-iV-allyl-A -o -methylbenzylamide to unsaturated esters was shown to be an effective method for producing RCM precursors <02SL1146> for piperidine synthesis, as was the addition of allylamine to the enantiomerically-enriched allylic epoxide 37 <02TL779> (Scheme 20). 

Amines usually undergo conjugate addition to unsaturated esters see Chapter 10. 

Conjugate addition of carbon nucleophiles to unsaturated esters, ketones, nitriles, sulfones and other activated double bonds is known as the Michael reaction. It is a very useful synthetic method for the formation of the carbon-carbon bond. 

Alternatively, isoxazolidin-5-yl acetates were obtained by reduction and acetylation of suitable isoxazolidin-5-ones, which, in turn, were prepared by diastereoselective Michael addition of hydroxylamines to unsaturated esters or by nucleophilic addition of enolates to nitrones and subsequent cyclization of the resulting hydroxylamines. For example, the two diastereomeric isoxazolidinones 552 were converted into thymidine analogues 590 (Scheme 146) <1997JOC7430, 1998T6587, 2000TL9239, 2005CRC775>. 

If carboxylic acid esters are readily available, they provide a convenient basis for the preparation of acid halides. Modified phosphorus halides, like 2,2,2-trichloro-l,3,2-benzodioxaphosphole can be applied successfully. This reagent forms first a 1,1-dichloroalkyl ether, which decomposes to the acid chloride (equation 16). The reaction conditions are rather drastic. For instance -butyl benzoate has to be heated for 4 h at 180 °C in order to get a 90% yield of benzoyl chloride. The only stable and isolable 1,1-dichloro ether is a,a-dichloromethyl methyl ether, which, as described above, is used as a mild reagent for the conversion of carboxylic acids to their chlorides. Similarly severe conditions are required if the chlorine or bromine adduct of triphenylphosphine is selected. This reaction may be catalyzed by BF3. It has been applied successfully to unsaturated esters and to the cleavage of lactones. 

This has been predominantly due to the lack of an efficient catalyst of sufficiently high activity and selectivity for the carbonylation of higher alkynes such as propyne [4]. Besides a high catalyst activity, not only is a high chemos-electivity of the carbonylation to unsaturated esters required, but a high regioselec-tivity of the carbonylation to the desired branched isomer (MMA) is, obviously, also essential. 

Mattson, A. E., Bharadwaj, A. R., Scheldt, K. A. The Thiazolium-Catalyzed Sila-Stetter Reaction Conjugate Addition of Acylsilanes to Unsaturated Esters and Ketones. J. Am. Chem. Soc. 2004, 126, 2314-2315. 

This more dramatic reaction starts with the simple conjugate addition of the Davies chiral version of LDA 89 to unsaturated esters first given in chapter 24. The lithium amide gives the Z-enolate of the product 90 and hence the adduct 91. The transition state 92 gives the correct stereochemistry.15... 

See page 1809, Section 6 for analogous conjugate additions to, -unsaturated, esters and nitriles... 

JV-Phenyl- or A-methyl-C-phenyl nitrones with (/ )-4-vinylsulfmyltoluene react with complete stereoselection in a process involving only the. Si-face of the alkene88. Cycloaddition of 4,5-dihydro-3//-pyrrole 1-oxide to unsaturated esters of chiral alcohols derived from camphor occurs with poor enantiofacial selection on the nitrone, but high diastereofacial preference on the alkene89. 

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