Mechanistic Rationale

Scheme 2. Mechanistic rationale for the oxidative deglycosidation of amphotericin B (1).

Interestingly, treatment of bicyclic imidate 5 (R = OMe) with lithium diisopropylamide at — 78 C, followed by addition of iodomethane and quenching into ammonium chloride solution, gives 2-methoxy-3-methyl-37/-azepine. In the absence of iodomethane, 2-methoxy-3i/-azepine (6, R = OMe) is produced. Rearrangement of the lithiated bicycle to a lithiated 2-methoxy-3//-azepine, followed by regioselective trapping by the electrophile, is the most likely mechanistic rationale. 

Interestingly, 3-(cyclohepta-2,4,6-trienyl)-3.//-azepine (20) in refluxing benzene undergoes a [1,5]-H shift and isomerization of the azepine, rather than the cycloheptatrienyl ring, to yield the 6-(cyc ohepta-2,4,6-trienyl)-3//-azcpine (21).118 A mechanistic rationale for this highly selective [1,5]-H shift has been discussed.118... 

Methyl 2,7- and 3,6-dimethyl-l//-azepine-1-carboxylate also show marked differences towards acid hydrolysis. The 3,6-dimethyl isomer, with 10% sulfuric acid at 20°C, forms the expected A,-(ethoxycarbonyl)-2,5-dimethylaniline in high yield (82%) however, the 2,7-dimethyl isomer requires more forcing conditions to effect ring contraction and yields a mixture of A-(methoxycarbonyl)-2,6-dimethylaniline (16% mp 103-105°C), A-(methoxycarbonyl)-2,3-dimethylaniline (1% mp 90-92°C), 2,6-dimethylphenol (1%), and 3,4-dimethylphenol (6% mp 66-67 C).115 A mechanistic rationale for these results has been proposed. 

Thermolysis of the azide 15, bearing an allyl side chain, is more complex, and in addition to ethyl 4-allylindole-2-carboxylate and ethyl 4-methyl-l//-3-benzazepine-2-carboxylate (16 oil), two unstable tricyclic aziridines 17 and 18 are produced.82 A mechanistic rationale for these results has been suggested. 

The 2-(2-pheriylvinyl) derivative 18 and the thienyl compound 20 cyclize exclusively at the alkene carbon, and at the thiophene ring, to give 3,4-diphenyl-l//-2-benzazepine (19) and 4-phenyl-6-//-thieno[3,2-e]-2-benzazepine (21), respectively.48 A mechanistic rationale for these results has been offered. This method has been extended to the synthesis of 7Z7-pyrido[3,4-t/]-, 7//-pyrido[2,3-t/]- and 77/-pyrido[4,3-r/]benzazepincs and to other thieno- and furo-fused 2-benzazepines.244... 

With potassium /m-butoxide in tetrahydrofuran, the dibromodihydro-3//-l-benzazepines 7 (R1 = H, F, Cl) undergo syn dehydrobromination to synthetically useful alkenyl bromides, e.g. 8 (R1 = Cl), accompanied by small amounts of debrominated materials, e.g, 9 (R1 = Cl), and the 3-fcrf-butyl ethers, e.g. 10b(R1 = Cl, R2 = -Bu).78 In contrast, with sodium hydroxide, or with sodium methoxide in dioxane/methanol, the yields of bromo compounds 8 decrease, and significant amounts of the methyl ethers, e.g. 10a (R1 = Cl R2 = Me), arc produced. A mechanistic rationale for these reactions has been offered. 

The only examples of fully unsaturated tetrazoloazepines, e.g. 3, have been prepared by an unusual and intriguing reaction involving the action of azide ion on 4,7-disulfonylbenzofurazan 1-oxides, e.g. I.148 A mechanistic rationale involving intramolecular 1,3-dipolar cycloaddition of an azidonitrile intermediate, e.g. 2, has been proposed. 

In contrast, in the absence of hydrogen at the Cl position of the cyclopropa[r]isoquinoline 5 (R R2 + H), prolonged heating produces the 5/7-benzazepincs 7, in moderate yields. A mechanistic rationale for these reactions has been proposed. 

A mechanistic rationale for the observed cw-selectivity has been proposed based on preorganisation of the Breslow-type intermediate and imine through hydrogen bonding 253, with an aza-benzoin oxy-Cope process proposed. Reaction via a boat transition state delivers the observed cw-stereochemistry of the product (Scheme 12.57). Related work by Nair and co-workers (using enones 42 in place of a,P-unsaturated sulfonylimines 251, see Section 12.2.2) generates P-lactones 43 with fran -ring substituents, while the P-lactam products 252 possess a cw-stereo-chemical relationship. 

A procedure for the preparation of allylic alcohols uses the equivalent of phenylselenenic acid and an alkene. The reaction product is then treated with r-butylhydroperoxide. Suggest a mechanistic rationale for this process. 

The reduction of allyl o-bromphenyl ether by LiAlH4 has been studied in several solvents. In ether, two products 12-A and 12-B are formed. The ratio 12-A 12-B increases with increasing LiAlH4 concentration. When LiAlD4 is used as the reductant, about half of product 12-B is monodeuterated. Provide a mechanistic rationale for these results. What is the predicted location of the deuterium in the 12-B Why is the product not completely deuterated ... 

Isoprene does not participate in the reaction under the above-optimized conditions. The combination of Ni(cdt) and c-Cy3P promotes the reaction. Unfortunately, however, the reaction results in a very complex mixture consisting of 1 1 and 1 2 adducts of acetaldehyde and isoprene. The 1 1 adducts (8a,b) are the minor products (Eq. 2) [12]. Except for 8e, all the products are out of material balance (vide supra, requiring one molecule of H2) and it is difficult to give any mechanistic rationale for their formation. 

A tandem palladium catalyzed multi-component approach has been devised providing direct access to for instance trisubstituted thiophenes from the simple starting material 3-iodothiophene 41. In a representative experiment, the substrate 41 was converted to the product 42 by treatment with ethyl acrylate and iodobutane in the presence of a catalytic system consisting of Pd(OAc)2, tri(2-furyl)phosphine (TFP), norbomene, and a base. A mechanistic rationale accounting for this outcome was also proposed <06OL3939>. 

Fig. 33 Product ratios in the Wagnerova Type II photooxygenation of 1-pentene and a mechanistic rationale for their formation.

A case of the addition of an allylstannane to aldehydes has been reported by Tagliavini to proceed with appreciable enantioselectivity (Scheme 6.15) [40]. A notable feature of the Zr-catalyzed transformations is that they proceed more rapidly than the corresponding Ti-catalyzed processes reported by the same research team (see Scheme 6.16). Furthermore, C—C bond formation is significantly more efficient when the reactions are carried out in the presence of 4 A molecular sieves the mechanistic rationale for this effect is not known. It should be noted that alkylations involving aliphatic aldehydes are relatively low-yielding, presumably as the result of competitive hydride transfer and formation of the reduced primary alcohol. 

Clay son, D.B. (1989). ICPEMC publication No. 17 Can a mechanistic rationale be provided for non-genotoxic carcinogens identified in rodent hioassays Mutation Res. 221 53-67. 

In contrast to that of solvents, the effect of the electrolyte solute, LiPFe, on the thermal decomposition of the cathode, LiCo02, was found to be suppression instead of catalyzation. The SHR of a partially delithiated cathode was measured in a series of electrolytes with various salt concentrations, and a strong suppression of the self-heating behavior was found as the concentration of LiPEe increased above 0.50 M. The mechanistic rationale behind this salt effect is still not well understood, but the authors speculated that the salt decomposition coated the cathode with a protective layer that acted as a combustion retardant. On the basis of these results, the authors recommended a higher salt concentration (>1.50 M) for LiCo02-based lithium ion cells is preferred in terms of thermal safety. 

Addition of perfluoroalkyl iodides to allyl chloride unexpectedly afforded polyfluori-nated alkenes RpCH2CH=CH2 aside from the expected adduct RfCH2CH(I)CH2C1. The ratio of these two products increased with increasing molar ratio of the reagents and temperature. A mechanistic rationale has been offered. ... 

Sulfoxide (N)-(+)-(151) undergoes a highly diastereoselective asymmetric cyclo-propanation with diphenyldiazomethane and diphenylsulfonium isopropylide to form the corresponding cyclopropanes (152) (Scheme 18). A mechanistic rationale to account for the observed stereoselectivities is illustrated for Ph,CN2 (153). ... 

For mechanistic rationales of reductions with NaHTe see Barton, D. H. R. Bohe, L. Lusinchi, X. Tetrahedron Lett. 1987, 28, 6609. 

One of the most compelling features of iminium ion catalysis is the proposed mechanistic rationale for the transformations, which leads to highly predictable reaction outcomes. Despite impressive advances and the plethora of reactions reported efforts to provide a detailed mechanistic understanding of the catalytic cycle are limited. The reported work has focussed on the Diels-Alder cycloaddition and has provided useful indicators that could be used in design of more active catalysts. 

The mechanistic rationale for the high stereoselectivity is provided by the intermediate production of the trans-iodonium species 279 and its collapse to the bridged oxonium species 280 prior to the introduction of the toxyloxy ligand. 

This catalyst system was the first to utilize both terminal alkynes and olefins in the intramolecular reaction. Although a mechanistic rationale for the observed stereoselectivity was not offered, the formation of the single stereoisomer 26 may be rationalized through the diastereotopic binding of the rhodium complex to the diene moiety (Scheme 12.3). This facial selective binding of the initial ene-diene would then lead to the formation the metallacycle III, which ultimately isomerizes and reductively eliminates to afford the product [14]. 

Provide a mechanistic rationale for the outcome, including stereoselectivity, of the... 

Possibly, the most common protocols used in the generation of azomethine ylides are those based on the in situ, fluorine-mediated desilyation of cyanoami-nosilanes developed by Padwa et al. (2). Typically, treatment of precursor 1 with AgF, in the presence of dimethyl acetylenedicarboxylate (DMAD), led to the formation of the intermediate cycloadduct 2, which was subjected to immediate DDQ oxidation to give pyrrole 3. The mechanistic rationale invokes fluoride-mediated desilyation to form the intermediate anion 4, which then undergoes loss of cyanide furnishing the corresponding azomethine yhde (Scheme 3.1). 

Finally, Ramsh and co-workers methylated 133 and isolated a 3 1 mixture of 135 and 136 albeit, in only 35% combined yield. The Russian authors offered a much different mechanistic rationale to account for these results than earlier work. Mannich reactions of 68 lead to markedly different results depending on the amine component (Schemes 6.36 6.37). For example, 137 was isolated in poor yield after refluxing a mixture of 68, benzylamine, paraformaldehyde, and acetic acid in methanol.The same material was also prepared from 138 under similar conditions. In a continuation of this work, Ramsh and co-workers investigated reactions using other primary and secondary amines. When 68 was treated with an excess of formalin and a secondary amine either 139 or 140 was isolated, albeit in fair to modest yield. However, some primary amines gave rise to the oxa-zolo[3,2-fl]l,3,5-triazines 141a-d, whereas other primary amines led to the... 

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