Intramolecular nucleophilic

The mechanism of this transformation is a matter of debate, and may vary with the structure of the heteroanalogous carbonyl compound employed. Although a Diels-Alder-type process is conceivable [246], a Lewis acid-induced addition of the silyl enol ether moiety in 2-453 followed by a cyclizahon through a nucleophilic intramolecular attack of the amine and subsequent elimination of methanol is assumed in this case [247]. 

According to the stepwise electrophilic reaction mechanism, the differences in the stereochemistries of the products from the reactions of alkenes with cyclic 49 and acyclic 51 disulfonium dications can be explained by the larger rates of the intramolecular reactions. In the case of a cyclic dication, the carbocationic center in intermediate 94, which is formed as the result of initial attack by a S-S dication on a double C=C bond reacts with nucleophile intramolecularly, thus conserving the configuration of the substituents at the double bond. On the other hand, an acyclic dication undergoes transformation to two separate particles (95 and dimethylsulfide) with a consequent loss of stereoselectivity. Additional experiments with deuteretad alkenes confirm that reaction is not stereoselective, lending further support to the stepwise mechanism (Scheme 36).106... 

In summary, it would appear that the oxidation of a catecholamine probably first involves the formation of a semi-quinone radical (this can be brought about by an one-electron transfer, e.g. from Cu++ ions,14 or by photoactivation 1) which rapidly undergoes further oxidation (e.g. with atmospheric oxygen) to an intermediate open-chain quinone (such as adrenaline-quinone) and then cyclizes by an oxidative nucleophilic intramolecular substitution to the amino-chrome molecule. Whilst the initial formation of a leucoaminochrome by non-oxidative cyclization of the intermediate open-chain quinone in some cases cannot be entirely excluded at the moment (cf. Raper s original scheme for aminochrome formation72), the... 

Sigman and Jorgenson490 have found that zinc(II) catalyzes the transesterification reaction between N- (/3-hydroxy ethyl) ethylenediamine and 4-nitrophenyl picolinate. This reaction involves a reactive mixed ligand complex (152) in which the zinc(II) ion perturbs the p/fa of the hydroxyethyl group of N-(/3-hydroxyethyl)ethylenediamine to provide a high effective concentration of the nucleophile. Intramolecular nudeophlic attack then occurs at the carbonyl group of p-nitrophenyl picolinate. This system provides a somewhat unique example of intramolecular... 

Oxidation with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) of the thiourea 51, derived from dopamine, gave the 1,3-benzothiazepine 53 in quantitative yield via a facile J-based nucleophilic intramolecular addition to the intermediate o-quinone 52 (Equation 9) <2005OBC2387>. 

Wrobel and Golfbiewski (67) interpreted the condensation in terms of a two stage reaction a Claisen-Schmidt condensation resulting in an amino alcohol (147) followed by nucleophilic intramolecular substitution of the OH group. Quick and Oterson (69) suggested a modification of the latter... 

The formation of these compounds may be explained by the following transformations. The weakly nucleophilic hexamethyldisilazane initially reacts at the carbon atom of the multiple bond, and fluoride ion elimination takes place in the new zwitterion, forming a terminal double bond. Further catalysis by the fluoride ion generates an active N-nucleophile intramolecular cyclization involving the latter leads to a four-membered heterocycle. 

The authors proposed a mechanistic explanation for these different behaviors. For the case of the free phenol cydization precursor 40a, an ionic mechanism via intermediate 44 leads to the nucleophilic intramolecular para substitution product 41a (Scheme 11). For the O-protected derivatives 40s-w, an alternative mechanism leads to the formation of the cation radical 45, which then participates in an intramolecular cydization to deliver an activated... 

In one of the last transformations in a multistep synthesis of 1,2-dihydro-8-ep/-vernolepin (43), nucleophilic intramolecular substitution at an iodomethyl group was promoted by heating an ester precursor with an equivalent of NaOAc in DMF (Equation (18)) <95TL3ii>. Molecular mechanics analysis of the precursor produced a minimum energy conformer that showed the hydroxyl substituent too distant from the iodomethyl group to have interfered with this high yield transformation. 

Tandem nucleophilic/intramolecular addition also occurs in the reaction of the imino-phosphorane 32 (R = C02Me, CN) with isocyanates and nucleophiles (X = O, S, NR) to give 33. ... 

Carbocyclic compounds can be formed by the nucleophilic intramolecular capture of a seleniranium intermediate of an olefinic bond. The carbonium ion which is formed as intermediate can react with another nucleophile or with the solvent. The first examples of these carbocyclization reactions were observed with dienes. Clive [105] reported that the reaction of the diene 203 with phenyl-selenyl chloride in acetic acid afforded the intermediate 204 which reacted with the solvent to give the bicyclic compound 205 (Scheme 31). Carbocyclization reactions were efficiently promoted by phenylselenyl iodide produced by diphenyl diselenide and iodine. As indicated in Scheme 31,Toshimitsu reported that the reaction of 1,5-hexadiene 206, in acetonitrile and water, afforded the acetamido cyclohexane derivative 209, derived from the cyclization of the seleniranium intermediate 207 followed by the reaction of the carbocation 208 with acetonitrile [106]. In several cases, carbocyclization reactions can be more conveniently effected by independently generating the seleniranium intermediates. A simple procedure consists of the reaction of trifluoromethane-sulfonic acid with j9-hydroxyselenides, which can be easily obtained from the... 

For reduction of PhC=C(CH2)4X (X = Cl, Br entries 13, 14) the relatively low half-wave potentials relate, for the bromide, to cathodic cleavage of the carbon-bromine bond, but for the chloride it is likely that the radical anion of the alkyne is produced, which allows nucleophilic intramolecular displacement of chloride (see Section II.A). 

Phenols are oxidized to the corresponding quinones or their derivatives. If an aromatic nucleus is present at a suitable position as a nucleophile, intramolecular oxidative phenol coupling occurs. Typical examples are shown in Schemes 9.58 [57], 9.59 [57], 9.60 ]58], 9.61 [59], 9.62 [60] and 9.63 [61]. 

Oxidation with DDQ of the thiourea 183 derived from dopamine gave the 1,3-benzothiazepine 185 in quantitative yield via S-based nucleophilic intramolecular addition to the o-quinone 184 <05OBC2387>... 

The 1,4-Michael addition on solid phase was studied using various nucleophiles. Intramolecular and tandem Michael additions have also been investigated. Several representative examples are given. Until now, only one example has been reported where the nucleophile has been attached to the resin. 

Oxazoles readily undergo Diels-Alder type cycloaddition across the 2,5-positions, in parallel with the behaviour of furans (18.7). Thiazole and imidazole do not show this mode of reactivity, however they do react with highly electrophilic alkynes via initial electrophilic addition to the nitrogen, then nucleophilic intramolecular cyclising addition (cf the comparable reactivity of quinohnes, 9.13). ... 

Nucleophilic intramolecular addition of a carbon-silicon bond onto a carbon-nitrogen iminium ion is the key step of a berbine synthesis <82CC769,83H(20)417>. Thus, treatment of the isoquinolinium salt (235) with caesium fluoride in ethanol afforded (+)-xylopinine (237), presumably via the betaine (236) (Scheme 45). A silicon-directed intramolecular cyclization of a A-acyliminium ion (238) was also the key step of Speckamp s synthesis of (+)-epilupinine as shown in Scheme 46 <85JOC40I4>. 

In an acid-base equilibrium, the Bronsted or Lewis acid adds to one of the carbonyl groups in the 1,4-dicarbonyl system (13) enabling a nucleophilic intramolecular attack by the second carbonyl group, to form 14 finally, the / -elimination, which is also acid-catalysed, occurs (14 -> 12) [6]. 

Competitive or preferential nucleophilic (trans) addition is specially important for late transition metals since, in general, they are good a-acceptors and efficiently activate alkenes or alkynes upon coordination. Coordinated X groups that have lone pairs (X = amido, alkoxide, etc.) may give a 1,2-cis addition product by nucleophilic intramolecular attack, depending on the availability of this lone... 

A related nucleophilic intramolecular displacement was reported for the preparation of 1,3,5-dithiazines 174 from... 

Similar rearrangements were observed on related substrates in the preparation of bis-norpenicillins [188a]. Competition from the sulfur atom in the nucleophilic intramolecular attack of the nitrogen atom to the carbenoid species could be repressed by oxidation to the sulfoxide or sulfone derivatives [188]. Unfortunately, these findings were of no use in penem synthesis. 

The Nicholas and Pauson-Khand reactions, as well as the bond-angle effect, have been combined in a single synthetic scheme to make more efficient use of the cobalt. This has been done in a synthesis of epoxydictamine 7.90 (Scheme 7.24)." The Nicholas reaction was employed, in which a carbocation 7.87, generated from acetal 7.86, was trapped by an allylsilane nucleophile intramolecularly, to form the eight-membered ring... 

The B aldwin rules indicate which cyclizations of acyclic precursors are favored and which are not [6-8]. It is important to note the substantial difference to the Woodward-Hoffimann mles [9-11], based on the theoretical concept staling which reactions are "allowed and which are forbidden by the orbital symmetry. The Baldwin rules are based on experimental observations and indicate the relative prrf-erence of the acyclic precursor to form cyclic compounds. Therefore, the expressions favored" and disfavored" indicate enCTgetically convenient and inconvenient cyclization. These rules refer predominantly to nucleophilic intramolecular reactions where the nucleophile approaches the C atom, which can be tetrahedral (tet, sp ), trigonal (trig, sp ) or diagonal (dig, sp). Based on experimental experience, they provide a particularly important guide for synthetic organic chemists. 

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