Addition, acyl

Acylation of Activated Double Bonds and of Triple Bonds Hydro-acyl-addition... 

Addition of Alcohols, Amines, Carboxylic Esters, Aldehydes, etc. Hydro-acyl-addition, etc... 

The analysis of polymeric and gaseous products of the reaction of PMMA and di-methylamine at low dimethylamine levels shows that there was a clean reaction that produced 1 eq of anhydride (NOT Amide) per 1 eq of dimethylamine and per 1 eq of MMA. Note that this is in most close agreement with pathway 2a- 3a (Figure 2) in which most of the MMA carbonyls have been converted to COOH or alkylammonium COO salts followed by closure to anhydride. This shows that direct acyl addition (2c— 3c) to form amide, or reaction of carboxylate with adjacent ester (2b- 3b) to form anhydride (which liberates MeOH after proton transfer, and requires only 0.5 eq. dimethylamine per MMA group) are not the predominant pathways under these conditions. The Flory limit effect is consistent with random initial MAA formation, which after cyclization to anhydride (Figure 2) eventually leads to some groups trapped between rings which remain in the uncyclized acid form. 

Type I Asymmetric Acyl Addition to 7r-Nucleophiles Steglich and Related Rearrangements and Additions to Silyl Ketene Acetals/lmines... 

Moving from rearrangements, condensation reactions were also presented. Condensation reactions occur when two reactive species condense with one another forming a new compound. The first was the aldol condensation (Scheme 8.9). Later, a more complex application of the aldol condensation was presented in the form of the Robinson annula-tion (Scheme 8.10). For both of these reactions, the underlying lessons relate to the ability to induce reactions and incorporate substitutions at carbon atoms adjacent to carbonyl groups. Similar reactivities of such carbon atoms can be utilized for alkylation (SN2) and acylation (addition-elimination) reactions as illustrated in Scheme 8.11. 

Comparison of SN2 and acyl addition-elimination reactions with methoxide as the leaving group. In the concerted SN2, methoxide leaves in a slightly endothermic step, and the bond to methoxide is largely broken in the transition state. In the acyl substitution, methoxide leaves in an exothermic second step with a reactant-like transition state The bond to methoxide has just begun to break in the transition state. 

A nice extension of this chemistry to sequential anionic/radical/anionic sequence was also provided [5, 9]. Normally after acyl addition and radical cyclization onto a C = C bond, the newly formed carbon radical is reduced to an organosamarium intermediate which is subsequently protonated. However, as depicted in Scheme 5, this organosamarium may be trapped in the presence of a ketone substrate, thus terminating this three-step process. In another demonstration of how such anions may be further exploited, substrates possessing vinyl ethers as the radical acceptor were found to under-... 

At the moment of their birth (i.e., when the excited singlet states of the aryl esters undergo lysis), the geminal radical pairs mustbe in positions that make their shape similar to that of their precursor ester the radical center of the acyl part is very near the oxygen atom of the aryloxy part, and all subsequent diffusion of the two species starts from this orientation. As a result, addition of an acyl radical to its aryloxy partner is favored spatially at the nearer adj acent ortho) position(s) than at the more distant meta and para positions. However, the ability of the acyl radical to add to each of the positions of an aryloxy radical is expected to depend on the energies of the adducts" ° (which are keto intermediates that enolize thermally with time to the eventual products Equation 13.5 shows an example of the keto intermediate for acyl addition to the ortho position of phenoxy). The spin densities at the 2-, 4-, and oxy-positions of 1-naphthoxy (and of phenoxy) from ESR measurements and HF/6-31G level calculations (in parentheses) are shown in Fig. 13.1. Those for the 2-naphthoxy radical by ESR measurements " and MNDO-UHF calculations are collected in Table 13.1. These considerations explain why the yields of products from addition at the meta positions are very low. 

Similar reactions have been carried out on acetylene.In an interesting variation, thiocarbonates add to aUcynes in the presence of a palladium catalyst to give a p-phenylthio a,p-unsaturated ester.Aldehydes add to alkynes in the presence of a rhodium catalyst to give conjugated ketones.In a cyclic version of the addition of aldehydes, 4-pentenal was converted to cyclopentanone with a rhodium-complex catalyst. An intramolecular acyl addition to an alkyne was reported using silyl ketones, acetic aid and a rhodium catalyst. In the presence of a palladium catalyst, a tosylamide group added to an alkene unit to generate A-tosylpyrrolidine derivatives. 

A variation that is more of an acyl addition (16-25) involves the reaction of an allylic alcohol with benzaldehyde. With a ruthenium catalyst and in an ionic liquid, the C=C unit reacts with the aldehyde, with concomitant oxidation of the allylic alcohol unit, to give a p-hydroxy ketone, PhCHO - -C=C—CH(OH)R PhCH(OH) CH(Me)COR. In another variation, formate esters add to alkenes using a ruthenium catalyst to give an alkyl ester via a formylation process. 

There are a number of variations of the condensation reaction of acid derivatives. The reaction between a cyclic ketone having a pendant alkynyl ester unit and tetra-butylammonium fluoride leads to cyclization to a bicyclic alcohol with an exocyclic allene moiety. A chain-extension reaction culminates in acyl addition of an ester enolate. The reaction of a p-keto ester, such as methyl 3-oxobutanote and EtZnCH2k leads to chain extension via a carbenoid-like insertion reaction (p. 803), which reacts with an aldehyde in a second step to give a methyl 3-oxopentanoate derivative with a —CH(OH)R group at C-2 relative to the ester carbonyl. ... 

A,Ai-Dimethylaniline reacts with aldehydes under photochemical conditions to give acyl addition via the carbon atom of one of the methyl groups.The reaction of PhNMe2 and benzaldehyde, for example, gave PhN(Me)CH2CH(OH)Ph upon photolysis. 

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