Synthesis of Spirocyclic Indolenines James, Michael J.; O'Brien, Peter; Taylor, Richard J. K. ...
Chemistry : a European journal,
February 24, 2016, Letnik:
22, Številka:
9
Journal Article
Recenzirano
This Review provides an in‐depth account of the synthesis of spirocyclic indolenines. Over the last 77 years, a wide array of diverse synthetic methods has been developed in order to generate these ...synthetically useful and biologically important spirocyclic scaffolds. The main synthetic strategies discussed are grouped into three main categories, namely interrupted Fischer indolisations, dearomatisation reactions of indoles and condensation reactions. The historical background, common synthetic challenges, current state‐of‐the‐art and future perspectives of this field are examined.
Another round: A detailed account of spirocyclic indolenine synthesis over the last 77 years is provided. The synthetic strategies described include interrupted Fischer indolisations, dearomatisation reactions of indoles and condensation reactions, as well miscellaneous processes. Common synthetic challenges associated with these strategies are also examined.
Medicinally relevant spirocyclic indolenines, carbazoles and quinolines can each be directly synthesised selectively from common indolyl ynone starting materials by catalyst variation. The high ...yielding, divergent reactions all proceed by an initial dearomatising spirocyclisation reaction to generate an intermediate vinyl–metal species, which then rearranges selectively by careful choice of catalyst and reaction conditions.
Medicinally relevant spirocyclic indolenines, carbazoles and quinolines can each be directly synthesised selectively from common indolyl ynone starting materials by catalyst variation (see scheme). The high yielding, divergent reactions all proceed by an initial dearomatising spirocyclisation reaction to generate an intermediate vinyl–metal species, which then rearranges selectively by careful choice of catalyst and reaction conditions.
A high‐yielding silver(I)‐ or copper(II)‐catalyzed dearomatizing spirocyclization strategy allows the conversion of simple aromatic compounds that contain ynone substituents, including indole, ...anisole, pyrrole, and benzofuran derivatives, into functionalized spirocyclic scaffolds. A high‐yielding asymmetric variant furnishes spirocyclic indolenines in up to 89:11 e.r.
Dearomatization: Simple achiral aromatic compounds that contain ynone substituents, including indole, anisole, pyrrole, and benzofuran derivatives, can be converted into complex chiral spirocyclic scaffolds. The silver(I)‐catalyzed dearomatizing spirocyclization typically provides the products in more than 95 % yield and up to 89:11 e.r.
Photocatalytic generation of phosphoranyl radicals is fast emerging as an essential method for the generation of diverse and valuable radicals, typically via deoxygenation or desulfurization ...processes. This Perspective is a comprehensive evaluation of all studies using phosphoranyl radicals as tunable mediators in photoredox catalysis, highlighting how two distinct methods for phosphoranyl radical formation (radical addition and nucleophilic addition) can be used to generate versatile radical intermediates with diverse reactivity profiles.
The structures and biological activities of naturally occurring 3‐alkenyl‐oxindoles are reviewed. Important man‐made3‐alkenyl‐oxindoles are covered, particularly those with pharmaceutical ...applications such as sunitinib (SU11248), the orally active receptor tyrosine kinase inhibitor marketed by Pfizer as Sutent®. Traditional synthetic approaches to 3‐alkenyl‐oxindoles are summarised and then recently developed tandem/telescoped synthetic routes are described.
The structures and biological activities of naturally occurring and man‐made 3‐alkenyl‐oxindoles are reviewed and recentlydeveloped tandem/telescoped synthetic routes are described.
Silica‐supported AgNO3 (AgNO3–SiO2) catalyzes the dearomatizing spirocyclization of alkyne‐tethered aromatics far more effectively than the analogous unsupported reagent; in many cases, reactions ...which fail using unsupported AgNO3 proceed effectively with AgNO3–SiO2. Mechanistic studies indicate that this is a consequence of silver nanoparticle formation on the silica surface combined with a synergistic effect caused by the silica support itself. The remarkable ease with which the reagent can be prepared and used is likely to be of much synthetic importance, in particular, by making nanoparticle catalysis more accessible to non‐specialists.
Nanoparticle catalysis: Silica‐supported AgNO3 catalyzes the dearomatizing spirocyclization of alkyne‐tethered aromatics far more effectively than the analogous unsupported reagent. Mechanistic studies indicate that this is a consequence of silver nanoparticle formation on the silica surface combined with a synergistic effect caused by the silica support itself.
The photocatalytic deoxygenation of sulfoxides to generate sulfides facilitated by either Ir(dF(CF3)ppy)2(dtbbpy)PF6 or fac-Ir(ppy)3 is reported. Mechanistic studies indicate that a radical ...chain mechanism operates, which proceeds via a phosphoranyl radical generated from a radical/polar crossover process. Initiation of the radical chain was found to proceed via two opposing photocatalytic quenching mechanisms, offering complementary reactivity. The mild nature of the radical deoxygenation process enables the reduction of a wide range of functionalized sulfoxides, including those containing acid-sensitive groups, in typically high isolated yields.
The dearomatization of 2-haloindole precursors allows access to indoleninyl halides, a hitherto underexploited functional handle with broad synthetic utility. Indoleninyl iodides have been shown to ...react via three distinct modes: hydrolysis, nucleophilic substitution, and cross-coupling. This allows a broad array of functionalized spirocyclic indole derivatives to be generated from a common starting material. They are also useful precursors to functionalized quinolines following migratory rearrangement and subsequent derivatization reactions.
The polycyclic core of the akuammiline alkaloids can be synthesized from simple tryptamine and tryptophol derivatives via a Ag(I)-catalyzed enantioselective dearomative cyclization cascade sequence. ...The complex tetracyclic scaffolds are prepared via a rapid, versatile, three-step modular synthesis from simple commercially available indole derivatives in high yields and enantiomeric excess (up to 99% yield and >99% ee).
PDF
