Introduction of substituents at

There are a wide variety of methods for introduction of substituents at C3. Since this is the preferred site for electrophilic substitution, direct alkylation and acylation procedures are often effective. Even mild electrophiles such as alkenes with EW substituents can react at the 3-position of the indole ring. Techniques for preparation of 3-lithioindoles, usually by halogen-metal exchange, have been developed and this provides access not only to the lithium reagents but also to other organometallic reagents derived from them. The 3-position is also reactive toward electrophilic mercuration. 

Entry Indole reactant Alkylating reactant Yield (%) Ref 

I I ndol-1 -ylmagnesium bromide 3-Bromopropene, benzene, 70 10-14hat20X [4] 

6 Benzyl indole-5-carboxylate Methyl 4-(bromomethyl)-3- 45 methoxybenzoate, DMF, 80°C [9] 

4-T etrahydrocarbazol-9-ylmagnesium bromide N,A -Dimethyl-3-chloropro- 50 panaminc [12] 

---

Enol ethers of 17-ketones are formed by pyrolysis of the corresponding dialkyl ketals and enol acetates are readily prepared by the exchange procedure.The latter derivatives are widely used as reactive intermediates for the introduction of substituents at C-16. 

Double silylation of the nitro fragment of substrate (372) would afford the [ > C=N(OSi)2]+ cation, which should be trapped. To hinder deprotonation of this cation, the substrate contains a bulky substituent R2 at the C-2 atom. A priori, based on the data on intermolecular C,C-coupling of the above-mentioned cations, it can be suggested that the introduction of substituents at the C-l atom should decrease the reactivity of the cation and can adversely affect the thermodynamics of such cations. Consequently, these substituents would hinder the generation as well as trapping of cationic intermediates. 

The l-oxa-2,4,5-cycloheptatrienes 602 and 603 were postulated to be intermediates in the rearrangement of certain (ethynylfuryl)oxiranes to furo[3,4-b]furans [251]. The replacement of the methylene groups of 1,2-cycloheptadiene (465) by SiMe2 groups and the introduction of substituents at the allene moiety allowed the preparation of isolable seven-membered ring allenes. Thus, Barton et ah [177] obtained 604 and Ando et al. [178] 605. A few reactions of these systems have also been studied [177, 252]. Both groups [178, 253] synthesized the [4.4]betweenallene 606 and determined its structure by X-ray diffraction. 

The t-butylammonium cation forms a relatively weak complex, which was attributed to steric repulsion. The stability of anilinium complexes is about the same as that of alkylammonium complexes. The introduction of substituents at the 2- and 6-positions increases the steric repulsion which results in a drop in binding constant. This effect is enthalpic in origin. These results show that variations in the group R have only a minor effect on the stability of complexes in which the crown ether has a fully exposed cavity. Furthermore, there is no relationship between the p-K.-value of RNHJ and the stability of the complex. 

Conformational inversion barriers of 5,10-substituted decalins (17) were determined by NMR, and MMI calculations were carried out to see whether the twist-chair (ct) or the boat-boat (bb), correspond to the higher barrier. The ct was found to be higher in cw-decalin (17, R = H), but the introduction of substituents at the ring junction is expected to raise the energy of the bb. The observed AG agreed with the calculated value for ct, which is about 5 kcal/ mol higher than that of bb when R = CH3 or OH (124). 

Electrophilic substitution of thianthrene takes place at C-2. No examples of even minor amounts of 1-mono-substituted product have been reported. Disubstitution gives 2,7- (usually) or 2,8-products. In a few cases, 2,6-derivatives have been claimed. The presence of a sulfoxide or sulfone unit greatly reduces the susceptibility of either ring to electrophilic substitution. Carbon-centered electrophilic addition to sulfur to produce 5-R-thianthrenium salts has been described rarely most examples of the formation of such salts have involved the thianthrene radical ion(l-t-). Treatment of thianthrene with alkyl/aryllithiums produces the 1-lithio-species, and these organometallic derivatives allow the introduction of substituents at this position. 

The haloboranes BH2C1, BH2Br, BHC12, and BHBr2 are also useful hydroborating reagents.124 These compounds are somewhat more regioselective than borane itself but otherwise show similar reactivity. The most useful aspects of the chemistry of the haloboranes is their application in sequential introduction of substituents at boron. The... 

The introduction of substituents at C3 and C5 leads, in general, to charge removal from the corresponding carbon atom, and a subsequent drift of Jt-charge over the ring towards it, depressing... 

---