Nitrogen anchimeric assistance

SCHEME 43.39. Kogen et al. s synthesis of (—)-virantmycin 217 stereospecihc chlorination through nitrogen anchimeric assistance. 

Dimethylaminoethane-2-ol (20) is a compound that, by virtue of its nucleophilic center (Me2NH+C2H40), is employed to convert protected segments bound to supports as benzyl esters into acids by transesterification into dimethylaminoethyl esters [C(=0)0C2H4NMe2] that are hydrolyzable by a dimethylformamide-water (1 1) mixture. Compound 20 readily forms esters from acid chlorides. The hydrolysis and esterification are facilitated by anchimeric assistance by the adjacent nitrogen atom (see Section 2.10). The amino alcohol also reacts with dichloromethane. 

Anchimeric assistance by the aUcoxyl oxygen lone pair promotes heterolytic S v 1 and reactions at nitrogen as well as homolysis of the N—Cl bond. A-Haloamides are also amidyl radical sources" but their heterolytic reactivity is known to involve positive, rather than negative, halogen ... 

Halogen displacement from 2-halo-tetrahydropyrans and -hexahydropyrimidines is extremely easy, being assisted, in the SnI process, by the electron pairs on the heteroatom (equation 124). 3-Halohexahydropyridines can also show accelerated halogen displacement (anchimeric assistance from nitrogen equation 125). Apart from these and other (normal) substitutions, eliminations of H—Hal are also commonly found. 

An interesting ring-expansion reaction of the tetracyclic oxazepine derivative 95 occurred to yield a 1,4-oxazocine derivative 96. The reaction mechanism was thought to involve anchimeric assistance of the nitrogen atom of the heterocycle (Equation 9) <1996J(P1)545>. 

An Sn2 reaction with anchimeric assistance (via formation of a bicyclic aziridinium ion intermediate) has been proposed for the nucleophilic substitution of trans-2-substituted 3-piperidinol mesylates by nitrogen nucleophiles with retention of trans... 

It was suggested that the imino nitrogen was suitably located tc provide anchimeric assistance for the expulsion of nitrogen to give the diaziridinium ion (30). Since A -phenyl-A -benzhydrylidene benzamidine (31) was stable to the reaction conditions, it was... 

We have depicted the pinacol rearrangement as a two-step process with an actual carbonium ion as intermediate. There is good evidence that this is so, at least when a tertiary or benzylic cation can be formed. Evidently the stability of the incipient cation in the transition state permits (SNl-lihe) loss of water without anchimeric assistance from the migrating group. This is, we note, in contrast to what happens in migration to electron-deficient nitrogen or oxygen. 

This influence of the nitrogen ion is known as neighbouring group participation or anchimeric assistance. 

Isolated ratio (cisjtrans) 11.0 the tran -isomer appears to be unstable, presumably because of the ability of nitrogen to anchimerically assist in the loss of chloride in the /ra .v-isomer. ... 

In deaminative reactions, the cyclopropyl cations 14 seem to be more developed than in thermolysis or solvolysis. The reason may be that the nitrogen molecule, the best known leaving group, is not dependent on the anchimeric assistance of the C2-C3 bond when it leaves the cyclopropyl ring. Numerous examples of deaminations are known, even those, where in the absence of a stabilizing substituent R,. j at the reaction center, cyclopropanes 15 are observed in addition to allylic products 13. " ... 

Pyridin-2-ylphosphonate esters (99) are hydrolysed via attack by water on the neutral form of the ester, with no detectable anchimeric assistance on the part of the pyridine nitrogen atom. ... 

Early attempts to prepare /i-nitrovinyl azides led to the formation of furoxans.20 The -/i-nitrovinyl azide 54 has however been isolated.56 Its thermolysis in benzene afforded the azirine 57 in 60% yield the same compound was obtained on photolysis, together with a small amount of the furoxan 56, which is ascribed to photochemical -Z isomerism, leading initially to 55 (Eq. 16). In the aromatic series it is known that o-nitro-aryl azides undergo anchimerically assisted nitrogen elimination, giving benzofuroxans.57... 

Thermal ring closures of o-azidoaldehydes and -ketones, like many other cyclizations involving azides adjacent to an a,j3-unsaturated function, involve a concerted process with concomitant loss of nitrogen rather than a nitrene reaction.184 Kinetic studies demonstrate unequivocally that the carbonyl group exerts substantial anchimeric assistance. For example, the... 

Collins has also criticized an earlier assumption, that nitrogen is detached to yiekl exclusively reactive, so called hot carbocations which, unlike solvolytic cold ions, are far less selective and so result in a set of various products Hot ions were assumably formed without anchimeric assistance, the charge being localized. Collins has shown that the unusual properties of cations formed in deamination reactions are retained after several Wagner-Meerwein rearrangements and 6,1,2-shifts But hot carbocations must lose their energy after one 6,2-hydride shift resulting in normal carbocations Collins considers the intermediate carbo-... 

A kinetics study has been performed on the aqueous iodine oxidation of the thiolactam (78). The rate of oxidation of (78) was found to be approximately 100 times that of a simple cyclic thioether, and this enhancement was ascribed to transannular anchimeric assistance provided by the nitrogen of the amide group <87JOC258i>. The thermal decomposition of the fused dioxetane (79) has been monitored by chemiluminescence decay, and this has been shown to follow first-order kinetics. The activation parameters have been calculated <83CL431>. Second-order rate constants for the quatemization of octahydro-lfl-azonine (9) and other azacycloalkanes with iodomethane in acetonitrile and methanol have been measured <68CCC1429>. The kinetics of the hydrogen-deuterium... 

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