Heteroarenes, silylation

Silylations of aromatic analogs including heteroarenes are known, although in some instances a small amount of non-directed product is formed. The addition of a hydrogen scavenger was found to increase the yield of product (Equations (98) and (99)).93... 

The silylation of heteroarenes was also reported [96]. Silylation of thiophene or furan with 11 occurs selectively at the ot-position in the presence of [Ir(COD) (OMe)]2/2-ferf-butyl-l,10-phenanthroline (tbphen, 17). Silylation of pyrrole or indole under the same conditions was unsuccessful presumably due to the presence of the acidic N-H bond. Accordingly, N-substituted pyrrole and indole undergo silylation with 11, to selectively give 3-substituted products (Scheme 7). 

Falck has recently reported dehydrogenative silylation of heteroarenes with triethylsilane (18) [97]. Coupling with the Si-H bond of triethylsilane, rather than the disilane Si-Si bond, in conjunction with the use of norbomene that presumably acts as a hydrogen acceptor, gives good yields with indoles, thiophenes, and furans, under relatively mild condition (80°C). Unlike the reaction shown in Scheme 7, silylation of indole did not require protection of the N-H group. 

The aromatic silylation of five-membered heteroarenes under the same conditions (catalyst, temperature, solvent) also proceeded in regioselective fashion. Both, thiophene and furane derivatives are exclusively silylated at the a-position, but 1-triisopropylsily 1-pyrrole and -indole each produce selectively ]3-silyl products (Equations 14.9 and 14.10). 

The alkylation reaction is limited to nitro-substituted arenes and heteroarenes and is highly chemoselec-tive nucleophilic displacement of activated halogens, including fluorine, was not observed. The regio-selectivity is determined by the bulkiness of the silicon reagent. With unhindered silyl derivatives a strong preference for ortho addition was observed, as in the example of equation (6). With bulkier reagents attack took place exclusively at the para position (Scheme 1). The success of this reaction, which could not be reproduced with alkali enolates, was attributed at least in part to the essentially nonbasic reaction conditions under which side processes due to base-induced reactions of nitroarenes can be effectively eliminated.12... 

A well-established pathway for the synthesis of silylated heteroarenes is the 1,3-dipolarophilic cycloaddition of alkynylsilanes (97a/189) with diazo compounds (261) or (262). Thus, TMS-phenylacetylene (97a) and diazomethane (261) form 3-TMS-4-phenylpyrazole (263), whereas bis(TMS)-acetylene (189) and 261 afford 3,4-bis-(TMS)-pyrazole (264). Ethyl diazoacetate (262) plus 189 give rise to 3,4-bis(TMS)-5-ethoxycarbonylpyrazole (265) in good yields (equation 121)151. The sterospecific formation of 263 via 1,3-dipolarophilic cycloaddition from 97a and 261 can be considered as... 

The iron-catalysed reaction of heteroarenes, including indoles, pyrroles, thiophene, and furan, with 3-methyl-2-quinonyl boronic acids allows the formation of alkylated products, such as (68), rather than the more usual alkenylated products. The unusual alkylation, at the 5-position, of oxindoles to give products such as (69) has been reported using the acid-catalysed reaction with benzylic alcohols in nitromethane. Silylation of indole, at the 3-position, to give (70) has been achieved using a cationic ruthenium(II) sulfide complex as a catalyst. A sulfur-stabilized silicon electrophile is formed resulting in a Wheland intermediate which is deprotonated by sulfur atom. ... 

The scope of the intermolecular alkylation of heteroarenes has been expanded to include pharmaceutically important pyridines and quinoHnes (Scheme 19.89) [131]. The reactions were performed at high concentration (0.8 M) with catalyst loadings as low as 1 mol%. Substitution ortho to the heterocyclic nitrogen was required for efficient alkylation at the other ortho position. In addition, increasing the bulk of this ortho substituent from methyl to isopropyl led to an increase in both the alkylation rate and the isolated yield of the alkylated product In that prospect silyl groups were found to be suitable temporary blocking groups. 

Falck reported an efficient iridium-catalyzed C-H functional-ization/silylation of N-, S-, and O- based heteroarenes including N-unsubstituted indoles under milder conditions in the presence of a slight excess of EtsSiH (3 equiv), as shown in eq 3. 

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