Rapid, Selective Ru-Sulfonate-Catalyzed Allylation of Indoles Using Alcohols as Substrates

Abstract

The Ru-catalyzed allylation of differing indole compounds using ArCH(OH)CHdCH 2 (Ar ) Ph, 2-CH 3 C 6 H 4 , 2-CH 3 OC 6 H 4 2-ClC 6 H 4 , and 1-naphthyl) is relatively fast (usually <30 min for 100% conversion) at ambient temperature in the presence of [Ru(Cp*)(CH 3 CN) 3 ](PF 6 ) + a sulfonic acid cocatalyst, RSO 3 H (R ) p-tolyl, a camphor fragment or CH 3 ). The new catalysts allow allyl alcohols rather than carbonates, halides, acetates, etc., to be used as substrates in this allylation chemistry, thereby avoiding the use of a (wasted) leaving group. The branched products are favored, and in a number of examples b/l ratios in excess of 20 are observed. The catalyst is selective in that there is little or no N-allylation. The use of acids such as CF 3 SO 3 H or HBF 4 results in slower and/or less selective reactions. Although phosphoric acid additives show some promise, carboxylic acids are much less effective or do not catalyze the reaction at all. The preformed isolated complexes [Ru(Cp*)(η 3 -C 3 H 5 )(RSO 3 ) 2 ] are efficient catalyst precursors; however, NMR experiments suggest that one of the active species is the monosulfonate cationic complex [Ru(Cp*)(η 3 -C 3 H 5 )(CH 3 CN)(RSO 3 )] + . Stoichiometric oxidative addition reactions are shown to be relatively rapid. New Ru(Cp*) complexes have been generated and characterized by NMR methods. DFT calculations suggest that the large b/l ratios observed have a structural basis in that the Ru-C(allyl) bond length for the substituted terminal allyl carbon, Ru-C(1), is relatively long. X-ray structures for Ru(Cp*)(η 3 -C 3 H 5 )(SO 4 ) and the dication [Ru(Cp*)(η 3 -C 3 H 5 )(H 2 O) 2 ] 2+ (as a camphor sulfonate salt) are reported.

Access to 3‐Oxindoles from Allylic Alcohols and Indoles

“…According to previous independent reports of Kitamura, Pregosin, and us, an overall plausible mechanism for the allylation of indoles 1 is depicted in Figure . It involves activation of allylic alcohol 2 by the protonated sulfonate fragment of ruthenium(II) intermediate I ; this is followed by oxidative addition and release of a water molecule.…”

Transition metal catalyzed nucleophilic allylic substitution: activation of allylic alcohols via π-allylic species

“…In the presence of 5 mol% of complex 4 and 5 mol% of camphor sulfonic acid, very fast allylation took place in acetonitrile at room temperature, and C3-substituted indoles were obtained with very high regioselectivity in favour of branched products (Scheme 46). 70 No N-allylation was observed in the case of unprotected indoles and C3-allylation also took place regioselectively from N-substituted indoles. Higher regioselectivities towards the branched isomers were obtained from bulky allylic alcohols, but the presence of a phenyl group at the C2-position led to higher formation of linear products.…”

“…The regioselective catalytic substitution was also efficiently performed with isolated p-toluenesulfonate or mesylate ruthenium complexes such as 8, suggesting [RuCp*(RSO 3 )(allyl)(MeCN)] + as active catalytic species. 70 Complex 8 was also a very good precatalyst for the C-allylation of cyclic 1,3-diketones. Thus, starting from aromatic allylic alcohol, the regioselective monoallylation of dimedone was achieved in high yield at room temperature in acetonitrile (Scheme 47).…”

Ruthenium(IV) Complexes Featuring P,O‐Chelating Ligands: Regioselective Substitution Directly from Allylic Alcohols

“…Notably, moderate heating was necessary to achieve full conversion of the starting material 5 a (Table 1, entries 1–3), thereby highlighting the lower activity which results from the presence of the electron‐rich phosphine as compared with our previous results based on analogous ruthenium precatalysts featuring an N,O chelate 16. The presence of the more electron‐deficient sulfonate moiety in C was expected to lead to more reactive ruthenium species and indeed, good reactivity and regioselectivity were obtained at room temperature using either acetonitrile or dichloromethane (Table 1, entries 4 and 5) 6b. Moreover, the reaction was faster and full conversion of 5 a occurred within six hours in dichloromethane.…”

“…Notably, the ruthenium complex C is closely related to the active species [RuCp*(RSO 3 )(allyl)(MeCN)][RSO 3 ] proposed by Pregosin and co‐workers when they used [ A + RSO 3 H] as a catalyst precursor (Figure 1). 6b…”