Substitution, intramolecular, with

Interesting results have been obtained in intramolecular acylation reactions involving pyrrole and thiophene derivatives. A muscone synthesis involves selective intramolecular acylation at a vacant a-position (Scheme 18) (80JOC1906). In attempts to prepare 5,5-fused systems via intramolecular acylation reactions on to a jS-position of a thiophene or a pyrrole, in some cases ipso substitution occurs with the result that rearranged products are formed (Scheme 19) (82TH30200). 

An a-halosulfone 1 reacts with a base by deprotonation at the a -position to give a carbanionic species 3. An intramolecular nucleophilic substitution reaction, with the halogen substituent taking the part of the leaving group, then leads to formation of an intermediate episulfone 4 and the halide anion. This mechanism is supported by the fact that the episulfone 4 could be isolated. Subsequent extrusion of sulfur dioxide from 4 yields the alkene 2 ... 

The inverse electron demand Diels-Alder reaction of 3-substituted indoles with 1,2,4-triazines and 1,2,4,5-tetrazines proceeds in excellent yields both inter- and intramolecularly. The cycloaddition of tryptophan 124 with a tethered 1,2,4-triazine produced a diastereomerically pure cycloadduct 125 <96TL5061>. 

Regiospecilic intramolecular cycloadditions of nitrones to sulfur-substituted dienes, with 3-sulfolene precursors, has been realized (Scheme 2.217). The stereochemical outcome of these reactions is affected by the structure of the substituent (sulfide or sulfone) in the diene and by the chain length connecting the diene and nitrone (a) and (b) (see Scheme 2.211). The bicyclic products obtained from these reactions have been converted to interesting heterocyclic compounds (709). 

Rhodium(n) carboxamidates are clearly superior to all other types of catalysts in effecting highly chemo-, regio-, diastereo-, and enantioselective intramolecular C-H activation reactions of carbenoids derived from diazoacetates. Specifically, Rh2(4Y-MPPIM)4 is the catalyst of choice for C-H activation reactions of simple primary and secondary alkyl diazoacetates. Likewise, Rh2(4Y-MACIM)4 thus far has been the most successful catalyst with tertiary alkyl diazoacetates, whereas for primary acceptor-substituted diazoacetates with a pendant olefin side chain, Rh2(4A-MEOX)4 has proved to be highly selective. 

Both inter- and intramolecular Heck reactions of indoles have been pursued and these will be considered in turn. Appropriately, Heck and co-workers were the first to use Pd-catalyzed vinyl substitution reactions with haloindoles [239]. Thus, l-acetyl-3-bromoindole (217) gave a 50% yield of 3-indolylacrylate 218. A similar reaction with 5-bromoindole yielded ( )-methyl 3-(5-indolyl)acrylate (53% yield), but 3-bromoindole gave no identifiable product. 

Low-temperature photochemical cyclization of alkynes bearing a bulky substituent, mediated by CpCo(CO)2, proceeds with CO insertion to give cyclopentadienone complexes. Higher reaction temperatures lead to cyclotrimerization. The intramolecular variant of this reaction gives the bicyclic cyclopentadienones 139 and 139 (equation 19)142. Cyclization of unsymmetrically substituted diynes with the chiral R CpCo(CO)2 (R = 8-phenylmenthyl) leads to the formation of a mixture of diastereomers modest diastere-oselectivity was found. 

Vinylketene complexes, generated by treatment of heteroatom-substituted carbene complexes with alkynes, can react intramolecularly with different nucleophiles to yield cyclic compounds (Figure 2.30, Table 2.20). Four- to ten-membered rings have... 

The formation of six-membered or larger rings by intramolecular C-H bond insertion normally requires the attacked position to be especially activated towards electrophilic attack [1157,1158]. Electron-rich arenes or heteroarenes [1159-1162] and donor-substituted methylene groups can react intramolecularly with electrophilic carbene complexes to yield six- or seven-membered rings. Representative examples are given in Table 4.8. 

Tamura et al. (170-172) discovered that, when reactions of ester-substituted nitrones with allylic alcohols are performed in the presence of an equimolar amount of titanium tetraisopropoxide under heating or at room temperature, transesterification takes place to form new nitrones bearing an inner alkene dipolarophile. The resulting nitrone substrates undergo regio- and stereoselective intramolecular cycloaddition reactions to give the ring-fused isoxazolidines (Scheme 11.52). This tandem transesterification/[3 + 2]-cycloaddition method leads to the selective... 

The principal disadvantage of the intramolecular cyclization approach using Michael addition of a cysteine-based thiol to dehydroalanine is its nonstereoselectivity. Similarly, even when using 3-bromoalanine derivatives in a halide-based substitution reaction with cysteine-... 

All types of olefins can serve as substrates. Suitable acyclic olefins include ethylene, terminal and internal monoenes up to and including tetrasubstituted-double bonds, and aryl-substituted olefins. With dienes (and polyenes) an additional, intramolecular reaction pathway becomes available which leads to cyclic olefins (Reaction 2). 

A review of intramolecular 4 + 3-cycloadditions of allyl cations has been presented.277 The 4 + 3-cycloaddition reaction of C(2)-substituted furans with 1,3-dimethyloxyallyl cations show high endo diastereoselectivity and a cis dia-stereospecificity.278 The tandem Peterson olefination/[4 + 3]-cycloaddition of tertiary alcohols (149) in the presence of filran and Lewis acids (TiCLt) furnishes cycloheptanes (150) in modest yields (Scheme 57).279 (Trimethylsilyl)methyl allylic sulfones (151) were used to investigate the scope and limitations of intramolecular 4 + 3-cycloadditions of allylic sulfones (Scheme 58).280 Lewis acid-catalysed 4 + 3-... 

Rates of oxidation of para-substituted arylphosphines with singlet oxygen show good correlation with the Hammett a parameter (p = —1.53) and with the Tolman electronic parameter. The only products are the corresponding phosphine oxides. However, for ortho-substituted phosphines with electron-donating substituents, there are two products, namely a phosphinate formed by intramolecular insertion and phosphine oxide. Kinetic analyses demonstrated that both products are formed from the same intermediate, a phosphadioxirane. VT NMR experiments showed that perox-idic intermediates can only be detected for highly hindered and very electron-rich arylphosphines 243... 

Reaction of N-substituted bromomethanesulfonamides with 2 equiv of potassium carbonate and an cr-haloketone, ester, or nitrile leads directly to the /3-sultams 187 substituted at the C-3 position by an EWG. This base-promoted condensation can be used with a-halo ketones, esters, and nitriles where a second Sn2 intramolecular displacement can operate in tandem fashion (Scheme 60). This domino alkylation sequence exhibits a reactivity order where ketone > nitrile > ester (Table 14). The process is particularly efficient when diethyl bromomalonate or 3-chloro-2-butanone are involved <2004CJC113>. 

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