Asymmetric 1,2-Migration at Vicinal Tetrasubstituted Stereocenters Constructed from α-Keto Imines.

A carbonyl-assisted asymmetric 1,2-migratory allylation through in situ generation of vicinal tetrasubstituted stereocenters is reported to access enantiopure α-amino ketones and amino alcohols with excellent yields and diastereoselectivities. In a remarkable divergence, despite higher steric hindrance, the allylation exclusively occurs on ketones over imines in the first step, followed by a face-selective 1,2-allyl transfer, thus highlighting an exciting interplay between two distinct electrophiles. The methodology distinguishes itself through its adaptability to gram-scale synthesis, showcasing broad functional-group tolerance and stereodivergence. Density functional theory (DFT) analysis led to a deeper understanding of its selectivity and mechanistic framework. Highlighting its transformative potential, the method was applied to the total synthesis of hapalindole alkaloids.

Synthesis of functionalized indoles via cascade benzannulation strategies: a decade's overview.

Indoles are one of the most prominent aromatic heterocycles in the organic chemistry field. Due to their widespread presence in various natural products, alkaloids, drugs, approved medicines, etc. the synthesis and functionalization of indoles are of great interest. This review emphasizes recent developments and techniques in the domino cascade cyclization process in the last decade starting from the various building blocks. In particular, this review depicts several intriguing benzannulation methods of creating a benzene ring on a pre-existing pyrrole nucleus in an inter/intramolecular fashion under metal-catalyzed/metal-free approaches. Different subsections focus on gradual timely developments in this complementary area and a detailed analysis of the mechanisms and reactivity patterns. As a complementary method, this review gives a significant incentive to various annulation strategies and also gives an overview of the remaining challenges and upcoming possibilities.

Construction of C2-indolyl-quaternary centers by branch-selective allylation: enabling concise total synthesis of the (±)-mersicarpine alkaloid.

Herein we report a branch-selective allylation strategy for accessing C2-indolyl-all-carbon quaternary centers using allylboronic acids. This approach boasts broad functional group tolerance, scalability, and relies on easily accessible allyl alcohol precursors. Importantly, the C3-position of the indole remains free, offering a handle for further synthetic refinement. Mechanistic pathways, corroborated by density functional theory (DFT), suggest the involvement of an indolenine intermediate and a Zimmerman-Traxler-like transition state during allylboration. Demonstrating its efficacy, the method was applied to the total synthesis of the (±)-mersicarpine alkaloid and enabled formal synthesis of additional alkaloids, such as (±)-scholarisine G, (±)-melodinine E, and (±)-leuconoxine.

Copper(I)-nitrene platform for chemoproteomic profiling of methionine.

Methionine plays a critical role in various biological and cell regulatory processes, making its chemoproteomic profiling indispensable for exploring its functions and potential in protein therapeutics. Building on the principle of rapid oxidation of methionine, we report Copper(I)-Nitrene Platform for robust, and selective labeling of methionine to generate stable sulfonyl sulfimide conjugates under physiological conditions. We demonstrate the versatility of this platform to label methionine in bioactive peptides, intact proteins (6.5-79.5 kDa), and proteins in complex cell lysate mixtures with varying payloads. We discover ligandable proteins and sites harboring hyperreactive methionine within the human proteome. Furthermore, this has been utilized to profile oxidation-sensitive methionine residues, which might increase our understanding of the protective role of methionine in diseases associated with elevated levels of reactive oxygen species. The Copper(I)-Nitrene Platform allows labeling methionine residues in live cancer cells, observing minimal cytotoxic effects and achieving dose-dependent labeling. Confocal imaging further reveals the spatial distribution of modified proteins within the cell membrane, cytoplasm, and nucleus, underscoring the platform's potential in profiling the cellular interactome.

An expeditious route to sterically encumbered nonproteinogenic α-amino acid precursors using allylboronic acids.

A diastereoselective allylation of N-tert-butane sulfinyl α-iminoesters using allylboronic acids is developed to obtain optically active non-proteinogenic α-amino acid precursors in good yields and diastereoselectivities. Gram-scale synthesis, broad tolerance of functional groups, excellent stereodivergence, post-synthetic modifications, and easy removal of the chiral auxiliary are some of the key highlights. The protocol is applicable to various amino acids and short peptides, resulting in the incorporation of these precursors at the N-terminal position.

A one-pot "back-to-front" approach for the synthesis of benzene ring substituted indoles using allylboronic acids.

Synthesis of only benzene ring functionalized indoles and poly-substituted carbazoles is reported via a one-pot triple cascade benzannulation protocol. Usage of differently substituted and readily accessible allylboronic acids as a 3-carbon annulating partner enables diverse aliphatic and aromatic substitution patterns, which is still a daunting task. This scalable synthetic protocol tolerates broad scope, thus enabling further downstream modifications. As an application, carbazole based natural products glycozoline and glycozolinol were synthesized.

Stereodivergent Total Synthesis of Hapalindoles, Fischerindoles, Hapalonamide H, and Ambiguine H Alkaloids by Developing a Biomimetic, Redox-Neutral, Cascade Prins-Type Cyclization.

A stereoselective, redox-neutral, Brønsted acid-catalyzed cascade Prins-type cyclization between indole and aldehyde is described to access several structurally diverse indole terpenoid scaffolds in a single step. Applying this concept, stereodivergent total syntheses of nine hapalindole-type alkaloids are accomplished. Key transformations include allylation using geometrically isomeric allylboronic acid followed by a p-toluenesulfonic acid mediated deprotection-cyclization cascade.

Transition-Metal-Free Redox-Neutral One-Pot C3-Alkenylation of Indoles Using Aldehydes.

The synthesis of sensitive ß-alkyl 3-vinylindoles having diverse functional groups with good selectivity remains a challenging task. Keeping the synthetic utility of 3-alkenylindoles in mind, we explored a unique approach to synthesize them from unprotected indoles in a domino fashion. A transition-metal-free C3-alkenylation of indole is reported by using sequential Brønsted acid/base catalysis. Several ß-substituted 3-alkenylindoles and conjugated 1,3-dienes are synthesized by direct coupling of indole and readily available aliphatic aldehydes. Excellent scalability and recycling of benzenesulfinic acid for successive alkenylation reactions up to five times make this method economically viable.