Direct Asymmetric Synthesis of α-Aminoimines from 1,2-Bis-N-Sulfinylimines by Using Allyl Boronic Acids.

A unique direct asymmetric synthesis of α-aminoimines is realized, through rapid and exclusive mono-allylation of chiral bis-N-sulfinylimines using allylboronic acids. The highly selective allylation was possible as electrophilic imine functional group in the product α-aminoimines remained unreactive towards allyl boronic acid nucleophiles. Notably, by varying the geometry and chiral auxiliary, all four isomers of the α-aminoimines were accessed from readily available precursors. A range of allyl nucleophiles, which are tricky to generate by other means possessing highly reactive functional groups also took part in this reaction, expanding the scope further. The applicability of the products α-aminoimines were further demonstrated by accessing a range of structurally diverse chiral cyclic and acyclic 1,2-diamines bearing adjacent stereocenters through addition of a second nucleophile or aza-Prins-type cyclization by exploiting the nucleophilicity of the tethered alkene moiety. Moreover, the leaving group aptitude of sulfinyl auxiliary attached to imine, was exploited to access valuable chiral α-aminonitriles under thermal conditions without employing any reagents. Detailed DFT calculation revealed a chair-like transition state likely operating for the allylboration reaction across imine.

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.

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.