Allylation of indoles

Nitrogen heterocycles undergo C-allylation in the presence of metalacyclic iridium-phosphoramidite catalysts. Recently, Yu and coworkers reported the C-allylation of indoles with the iridium catalyst derived from LI [86] and from phosphoramidites containing 2-methylindoline- and 2-methyl-l,2,3,4-tetrahydro-quinoline as the amino group (Table 4) [87]. No N-allylation was reported. However,... 

Al-allylation of indoles and other azoles in the presence of iridium catalysts has been reported recently and is discussed in Sect. 5.3. 

A few recent examples of related C-C bond-forming reactions, all involving a palladium-catalyzed C-H activation step at arenes, will be mentioned. Salts are produced in these reactions, or acetic acid, as in the first example. Allylation of indoles at the 3-position was achieved by using palladium acetate, and bipyridine and allylic acetates as the reactants (Scheme 5) [19]. 

In one of the first papers on the subject, Billups et al. (80SC147) reported that the Pd(0)-catalyzed allylation of indole 96 with allyl acetate gave N-allyl- (97) and 3-allylindole (98) plus the diallylation product 99 (Scheme 21). They also showed that the yV-allyl isomer 97 rearranged under Pd(0) catalysis to the C-3 isomer 98, thus indicating that the formation of 98 was thermodynamically controlled (C > N). The work of Billups also includes the use of allyl alcohol instead of allyl acetate in the Tsuji-Trost reaction. 

Allylation of indole 160 (obtained from indole in 85% overall yield, five steps) with allyl bromide in the presence of CS2CO3 led directly to l-allyl-2-ethynyl-l/f-indole 161 with loss of the trimethylsilyl group in the same reaction (Equation 29) <2002S1810>. 

Under palladium catalysis, triethylborane promotes the C(3)-selective allylation of indoles and tryptophans using a wide structural variety of allyl alcohols (Equation 124) <2005JA4592>. The yields of allylation are excellent and in most cases exceed 80%. 

In this presentation, reductive a-allylation of indoles and reductive diallylation of lactams with allylic boranes as well as a new way to isoquinuclidine structures are described. 

Data obtained allow us to propose the following mechanism of the reductive a-allylation of indoles by allylboranes ... 

Allylation. The Pd salt in the presence of 6-diphenylphosphino-2-pyridone catalyzes C-allylation of indoles (at C-3) and pyrroles (at C-2) with allyl alcohol in toluene at 50°, generating water as the only byproduct. The key to activation of the allylating agent is by H-bonding. 

A palladium-catalyzed allylation of indoles with allyl carbonates furnished 3-alkylated indoles <04OL3199>. An intramolecular variation with indolyl carbonates provided a novel synthesis of tetrahydro-p-carbolines and pyrazinoll,2-a indoles. 

Kimura M, Futamata M, Mukai R, Tamaru Y (2005) Pd-Catalyzed C3-selective Allylation of Indoles with Allyl Alcohols Promoted by Triethylborane. J Am Chem Soc 127 4592... 

In 2005, Ricci and coworkers published the first organocatalytic enantio-selective Friedel-Crafts allylation of indoles with nitroalkenes utilising simple thiourea 66. In general, moderate yields and enantioselectivities were observed for this difficult transformation, utilising 20 mol% catalyst... 

SCHEME 23.37 Allylation of indol using allylboron dichloride. 

The direct ruthenium catalysed allylation with allylic alcohol derivatives of various aromatic compounds and heterocycles such as furans and thiophenes was performed by Nishibayashi with cationic thiolate-bridged diruthenium(III, II) catalysts. The reaction is consistent with an electrophilic aromatic substitution by the electrophilically activated allyl moiety [68]. Allylation also takes place with the alkene metathesis Grubbs catalyst [69]. More importantly using (phosphine-sulfonate)ruthenium(II) catalyst Bmneau et al. have recently shown that allyl alcohols are activated generating an allyl-ruthenium(IV) intermediate leading to C3-allylation of indole with high regioselectivity in favour of the branched allyl derivative [(Eq. 84)] [167]. 

---