New Perspectives in the Indole Ring Functionalization using 2‐Indolylmethanols

Abstract

2‐Indolylmethanols have been recently involved in several processes dealing with indole functionalization. These compounds, upon activation by Brønsted or Lewis acids, generate a bidentate electrophilic system amenable to react at the 3‐position or at the benzylic site with a wide range of nucleophilic reagents. The functionalization pattern is affected by the nature of the substituents at the carbinol unit and also depends on the nature of the nucleophile used. Nucleophilic reactants bearing a remote electrophilic site in their structure can be involved in a further ring closure ultimately leading to polycyclic derivatives. This review article summarizes some fundamental aspects of the chemistry of 2‐indolylmethanols with particular attention to those related to asymmetric synthesis.

Palladium-Catalyzed Aminocyclization–Coupling Cascades: Preparation of Dehydrotryptophan Derivatives and Computational Study

“…As displayed in Table , the reaction has been applied to substrates 9 with primary-, secondary-, and tertiary-alkyl groups at the alkynyl terminal position. Additionally, both protected and unprotected carbinol-type substituents were tolerated at that position, leading to the expected 2-indolylmethanols in moderate yields (entries 2, 5–6), and the incorporation of a cyclohexenyl substituent was also successful (entries 7 and 10). The particular examples of entries 4–6 and 8–9 provide a precedent for the introduction of tertiary alkyl groups, prevalent in natural and otherwise interesting dehydrotryptophan derivarives. − , Furthermore, the reaction could also be applied to the triethylsilyl (TES)-substituted substrate 9k (Scheme ) to yield a C-2-unsubstituted dehydrotryptophan 12 as a result of an aminocyclization–alkenylation cascade and concomitant desilylation.…”

Cross‐Dehydrogenative Coupling Reactions between Phenols and Hetarenes: Modern Trends in Cross‐Coupling Chemistry of Phenols

“…Shi et al developed an enantioselective synthesis of axially chiral indolyl-naphthols by the organocatalytic asymmetric coupling of 2-naphthols with 2-indolylmethanols bearing two aryl substituents via the umpolung strategy, [69] whereby the C3 position of the 2-indolylmethanol is converted from a nucleophilic to an electrophilic character under the action of an acid. [70,71] In the presence of a catalytic amount of a chiral phosphoric acid (CPA) in toluene at 0 °C, various indolyl-naphthols were obtained in excellent yield and enantiomeric excess (ee) (Scheme 25). In the first step, the dehydration of indolylmethanol occurred under acid conditions leading to a stabilised carbocation with two plausible electrophilic sites which could be attacked by the nucleophile.…”

Diversity synthesis of indole derivatives via catalyst control cyclization reaction of 2-indolylmethanols and azonaphthalene

“…Two main reaction patterns of 2-indolylmethanols have been developed (Scheme 1). 3 Shi and other groups have made great contributions and developed several transformations using 2-indolylmethanols, such as substitutions 4 and [3 + 2], 5 [3 + 3], 6 and [4 + 3] cyclizations. 7 In the reported studies, the C3-position of the 2-indolylmethanols usually displays electrophilicity.…”