Alkylation mechanistic considerations

Synthetic applications as well as mechanistic considerations were reviewed recently24. Extension of the methodology to the seven-membered ring resulted in the first asymmetric synthesis of chiral benzazepines by alkylation with primary alkyl halides (92-96% ee) in 57-82% yield25. 

The same disconnection 41 can be used for carboxylic acids with CO2 as the electrophile for a Grignard reagent 40. Dry ice (solid CO2) is particularly convenient for these reactions. Switching polarity by FGI to the nitrile 42, the same disconnection now uses cyanide ion as the nucleophile but the same alkyl halide 39 that was used to make the Grignard reagent. Mechanistic considerations should decide between these alternatives. 

Treatment of aromatic carboxaldehyde (diaminomethylene)hydrazones (105) with hot acetic anhydride or benzoyl chloride affords l,4-diacyl-3-acylamino-5-ary 1-4,5-dihydro- 1H-1,2,4-traizoles (106) in 75-95% yields. In contrast, when the 4-pyridine analog of 105 was employed, the unusual hemianimal triazole derivative (107) was obtained. The structures of the novel compounds were determined by spectral methods and in several cases by x-ray structural analysis. Mechanistic considerations are discussed [95M733]. The oxazole-1,2,4-triazole (108) was prepared by cyclization of the corresponding oxazolecarbonyl-thiosemicarbazide with bicarbonate, alkylation at the sulfur and oxidation to the sulfoxide with MCPBA [95JHC1235]. 

Alkyl-3-fluoro-3Zf-diazirines have become more readily available since the exchange of halogen in 3-alkyl-3-halo(chloro or bromo)diazirines by fluoride was developed" (for mechanistic consideration of this process, see refs 49 and 50, for 3-bromo-3-trifluoromethyldiazirine, see ref 47). Until now only a few 1-alkyl-1-fluorocyclopropanes la and Ib have been prepared by this method (see Houben-Weyl, Vol. E19b, p 1028). 

Ethyl ethylphosphonothioate with DDC gives the (+)-anhydride 93(Z = S). From mechanistic considerations, the anhydride should have the S -configuration at the thiophosphoryl phosphorus with inverted configuration, i.e. S, at the phosphoryl phos-phorus. A similar process (Scheme 17)(Z = Se) operates for the dehydration of O-alkyl ethylphosphonoselenoates with DCC when (-)-acid esters yield (+)-anhydrides. ... 

Reaction of alkyl bromides with Zn Kinetic and mechanistic considerations... 

To conclude with all of these mechanistic considerations, we have to point out that the experimental evidence collected, both for alkyl and aryl systems, goes against the possibility of multiple mechanisms [236]. Radicals have been detected on primary carbons. No sign of inversion (or retention) was detected in the stereochemical course of the reaction. For aryl systems, Hammett plots reveal also mechanistic homogeneity in all the range of 6 covered by substituents. 

Martmez-Asencio A, Ramon DJ, Yus M (2011) W-alkylation of poor nucleophiUc amines and derivatives with alcohols by a hydrogen autotransfer process catalyzed by copper(ll) acetate scope and mechanistic considerations. Tetrahedron 67(17) 3140-3149... 

Detailed mechanistic studies have been carried out on aminolysis of substituted aryl acetates and aryl carbonates. Aryl esters are considerably more reactive than alkyl esters because the phenoxide ions are better leaving groups than alkoxide ions. The tetrahedral intermediate formed in aminolysis can exist in several forms which differ in extent and site of protonation ... 

ATRP, other factors, such as solvent and temperature, must also be taken into consideration. Typical monomers and alkyl halide initiators that are used in ATRP are shown in Scheme 5 [47], The copper complex is perhaps the most important component of this catalytic system because it regulates the dynamic equilibrium between dormant and active species. In this article, structural and mechanistic aspects of copper-catalyzed ATRP are discussed. 

Hydrolyses of alkyl halides and arenesulfonates have long been known to be micelle-inhibited (Gani et al., 1973 Lapinte and Viout, 1973, 1979) but now k+/k < 1, except for hydrolysis of methyl benzenesulfonate which involves extensive bond making in the transition state (Al-Lohedan et al., 1982b Bunton and Ljunggren, 1984). Thus values of k+/k < 1 seem to be characteristic of hydrolyses in the SN1-SN2 mechanistic spectrum which involve considerable bond breaking in the transition state, and k+/k is very low for hydrolyses of diphenylmethyl halides where the transition state has considerable carbocation character (Table 8). 

Equipped with these reference trends for steric and electronic effects, one is prepared to survey more general classes of electrophilic aromatic substitution on benzocycloalkenes. Such reactions include nitration, halogenation, sulfonation, and alkylation. Each has its own mechanistic peculiarities, but their product distributions can be rationalized by consideration of the appropriate reference. 

In this review, we focus mainly on the preparative utility of organic peroxides, and only few mechanistic investigations are discussed. This review covers synthetic methodologies for the preparation of alkyl hydroperoxides and dialkyl peroxides (Section II) and the synthetic use of these peroxides in organic chemistry (Section III). In Section II, general methods for the synthesis of organic hydroperoxides and dialkyl peroxides are discussed, as well as the preparation of enantiomerically pure chiral hydroperoxides. The latter have attracted considerable interest for asymmetric oxidation reactions during the last years. 

The overall mechanistic picture of these reactions is poorly understood, and it is conceivable that more than one pathway may be involved. It is generally considered that cycloheptatrienes are generated from an initially formed norcaradiene, as shown in Scheme 30. Equilibration between the cycloheptatriene and norcaradiene is quite facile and under acidic conditions the cycloheptatriene may readily rearrange to give a substitution product, presumably via a norcaradiene intermediate (Schemes 32 and 34). When alkylated products are directly formed from the intermolecular reaction of carbenoids with benzenes (Scheme 33 and equation 36) a norcaradiene considered as an intermediate alternatively, a mechanism may be related to an electrophilic substitution may be involved leading to a zwitterionic intermediate. A similar intermediate has been proposed143 in the intramolecular reactions of carbenoids with benzenes, which result in substitution products (equations 37-40). It has been reported,144 however, that a considerable kinetic deuterium isotope effect was observed in some of these systems. Unless the electrophilic attack is reversible, this would indicate that a C—H insertion mechanism is involved in the rate-determining step. 

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