Addition-elimination reactions, table

The solid-phase synthesis of the 2(lff)-pyrazinone scaffold is based on a Strecker reaction of commercially available Wang amide linker with appropriate aldehyde and tetramethylsilyl (TMS) cyanide, followed by cyclization of a-aminonitrile with oxalyl chloride resulting in the resin linked pyrazinones. This approach allows a wide diversity at the C-6-position of pyrazinone scaffold (Scheme 35, Table 1). As it has been shown for the solution phase, the sensitive imidoyl chloride moiety can easily undergo an addition/elimination reaction with in situ-generated sodium methoxide affording the resin-linked... 

As we have seen (Section 4, p. 191) the range of effective molarities associated with ring-closure reactions is very much greater than that characteristic of intramolecular general acid-base catalysis the main classification is therefore in terms of mechanism. By far the largest section (I, Tables A-D) gives EM s for intramolecular nucleophilic reactions. These can be concerted displacements (mostly at tetrahedral carbon), stepwise displacements (mostly addition-elimination reactions at trigonal carbon), or additions, and they have been classified in terms of the nucleophilic and electrophilic centres. 

Ethoxymethylene)-2-phenyl-5(47/)-oxazolone 404, readily available from hippuric acid and triethyl orthoformate, has also been used as a starting material for other unsaturated oxazolones via addition-elimination reactions. Nitrogen nucleophiles are most commonly used and amines give rise to 4-(aminomethyl-ene)-2-phenyl-5(4//)-oxazolones 405 (Scheme 7.130 Table 7.37, Fig. 7.48) which, in many cases have been evaluated as antihypertensives. 

Table 7-2 summarizes kinetic data for the reaction of O2 with esters, diketones, and carbon dioxide.35,37-39 Esters react with superoxide ion to form diacyl peroxides or the carboxylate and the alcohol. Initial reaction occurs via a reversible addition-elimination reaction at the carbonyl carbon (Scheme 7-9). This conclusion is supported by the products that are observed in the gas-phase reaction of O2 with phenyl acetate and phenyl benzoate, which has been studied by Fourier-transform mass spectrometry.40 in effect, there is a competition between loss of O2 and loss of the leaving group. Carbanions are poor leaving groups, so that simple ketones without acidic a-hydrogen atoms are unreactive. The KC(O)OO- radical should be a reactive intermediate for the initiation of the autoxidation of allylic hydrogens (see Chapter 5). 

Conjugated dienones are found in nature [14], and both conjugated tram, trans-dienoes [15] and conjugated cis-trans dienones [16] are prepared easily in high stereospecific manner but in modest yields. Brown etal[ 7] have developed the conjugate addition-elimination reaction of B-l-alkenyl-9-BBN with the commercially available 4-methoxy-3-butene-2-one to provide the corresponding conjugated tram, tram-dienones in essentially the quantitative yields (Eq. 7.8 Table 7.17) [17]. 

We have just seen that there are two steps in a nucleophilic addition-elimination reaction formation of a tetrahedral intermediate and collapse of the tetrahedral intermediate. The weaker the base attached to the acyl group (Table 16.1), the easier it is for both steps of the reaction to take place. 

Addition-elimination reactions may be carried out under either basic or acidic conditions. We have seen how additions of nucleophiles to aldehydes and ketones (Sections 17-5 through 17-9 Table 17-4) may be catalyzed by either bases or acids. The same is true for additions of nucleophiles to carboxylic acid derivatives. Eliminations from the tetrahedral intermediate are similarly catalyzed Recall that this process is mechanistically just the reverse of addition therefore, the same catalytic effects are observed. Let us examine the roles of both base and acid in detail. 

Table I Leaving Groups in the Addition-Elimination Reaction...

A number of compounds of the general type H2NZ react with aldehydes and ketones m a manner analogous to that of primary amines The carbonyl group (C=0) IS converted to C=NZ and a molecule of water is formed Table 17 4 presents exam pies of some of these reactions The mechanism by which each proceeds is similar to the nucleophilic addition-elimination mechanism described for the reaction of primary amines with aldehydes and ketones... 

The reaction of benzenesulfomc acid with sodium hydroxide (first entry m Table 24 3) proceeds by the addition-elimination mechanism of nucleophilic aromatic substi... 

The reaction of benzenesulfonic acid with sodium hydroxide (first entry in Table 24.3) proceeds by the addition-elimination mechanism of nucleophilic aromatic substitution (Section 23.6). Hydroxide replaces sulfite ion (S03 ) at the carbon atom that bear s the leaving group. Thus, p-toluenesulfonic acid is converted exclusively to p-cresol by an analogous reaction ... 

Sulfur-stabilized ylides underwent photodriven reaction with chromium alkoxy-carbenes to produce 2-acyl vinyl ethers as E/Z mixtures with the E isomer predominating (Table 22) [ 121-123]. The reaction is thought to proceed by nucleophilic attack of the ylide carbon at the chromium carbene carbon followed by elimination of (CO)5CrSMe2. The same reaction occurred thermally, but at a reduced rate. Sulfilimines underwent a similar addition/elimination process to produce imidates or their hydrolysis products (Table 23) [ 124,125]. Again the reaction also proceeded thermally but much more slowly. Less basic sulfilimines having acyl or sulfonyl groups on nitrogen failed to react. 

Table 9.1). The rate of dehydrobromination from the intermediate bromoalkenes follows the pattern 2-bromoalkenes > Z-l-bromoalkenes > E- -bromoalkenes the corresponding chloro derivatives react more slowly. For optimum yield, the reaction temperature should be <100°C to reduce decomposition of the catalyst, and the concentration of base should be kept low to prevent isomerization of the resulting alkynes. [3-Elimination of HBr from 1,2-dibromo-1 -phenylethane can be controlled to yield 1-bromo-l-phenylethene in 83% yield [15]. The addition of alcohols and diols have a co-catalytic effect on the elimination reaction, as the alkoxide anions are transferred more effectively than the hydroxide ions into the organic phase [13]. 

This reaction occurs rapidly at room temperature using a small excess of alkyne and either pinacol- (HBpin) or catecholborane (HBcat). When an excess of borane was used, the Z/E ratio of the products was slowly eroded, eventually attaining a thermodynamic distribution of isomers. Equilibration presumably occurs via addition/elimination of excess Rh-H. Miyaura s method provides a useful synthetic complement to knovm cis-hydroboration methods. Under optimized conditions, good yields and high stereoselectivity (>90 10) were achieved for a variety of alkenylboronates (Table 9.8). The best selectivities were generally obtained with the use of catecholborane and Et3N as an additive. As in related reactions, the presence of base seems to suppress undesired reaction pathways. 

Discrepancies in the enantioselectivity reported for the same lithium amide and reaction conditions may be due to different enantiomeric purity of the lithium amides (Table 6, entries 1 -3,4-6 and 7-9 and Table 7, entries 3-5) . Interestingly, for the elimination of the cw-epoxides enantioselectivity is higher in benzene than in tetrahydrofuran (Table 6, entries 1 and 3.12 and 13 and 14 and 15) whereas for that of the trans-epoxide the situation is reversed (Tabic 7, entries 2 and 6). The enantioselectivity of the elimination of the /rans-epoxide can be raised significantly through addition of DBU (Table 7, entries 6 and 7). 

Starting with 2,4-diphenyl-1,3,5-triazine and KNH2-NH3, adduct 63 (Table XIII) is formed.116 The reaction mixture slowly leads to 2-amino-4,6-diphenyI-l,3,5-triazine by a mechanism that is shown by l5N labeling to consist of an addition-elimination process. Therefore, adduct 63 is likely to be a true reaction intermediate for the Chichibabin reaction. Although a related substrate, 2-methyIthio-4,6-diphenyl-1,3,5-triazine, gives the 2-amino derivative exclusively by the ANRORC mechanism, which is likely to involve the addition of NH2" to a phenyl-bearing position in the initial step, the formation of such adducts as 64 has not been reported.116... 

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