Search

An unprecedented enantioselective synthesis of spiro‐γ‐lactams via a sequential C−H olefination/asymmetric [4+1] spirocyclization under a simple CoII/chiral spiro phosphoric acid (SPA) binary system is reported. A range of biologically important spiro‐γ‐lactams are obtained with high levels of enantioselectivity (up to 98 % ee). The concise, asymmetric synthesis of an aldose reductase inhibitor was successfully achieved. Notably, contrast to previous reports that relied on the use of cyclopentadienyl or its derivatives (achiral Cp*, CptBu, or chiral Cpx) ligated CoIII complexes requiring tedious steps to prepare, cheap and commercially available cobalt(II) acetate tetrahydrate was used as an efficient precatalyst. [ABSTRACT FROM AUTHOR]

Palladium-catalyzed asymmetric functionalization of unbiased methylene C(sp3)–H bonds is a long-standing challenge. Here, we report a Pd(II)-catalyzed highly enantioselective arylation of unbiased methylene C(sp3)–H bonds enabled by a strongly coordinating bidentate 2-pyridinylisopropyl (PIP) directing group and an easily accessible 3,3′-F2-BINOL chiral ligand. The use of aryl iodides with the combination of 3,3′-F2-BINOL was beneficial for high enantiocontrol. A range of aliphatic amides and aryl iodides were tolerated, providing the desired arylated products in high enantioselectivities (up to 96% ee). The PIP directing group could be removed under mild conditions without erosion of enantiopurity. [ABSTRACT FROM AUTHOR]

Summary of main observation and conclusion: Copper‐catalyzed intramolecular N—H/C—H annulation with alkynes has been developed. A variety of densely functionalized heterocycles, such as pyrrolo[1,2‐a]indoles, indolo[1,2‐c]quinazolin‐2‐ones, oxazolo[3,4‐a]indoles, and imidazo[1,5‐a]indoles, were synthesized in an atom‐ and step‐economical manner, owing to the high modularized feature of aniline moiety, the linker moiety, as well as the alkyne moiety. By simply changing the oxidant from di‐tert‐butyl peroxide (DTBP) to 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO), the reaction could readily be transformed to the aminooxygenation pathway, which grabs one oxygen atom from the TEMPO to generate 5‐aroyl‐pyrrol‐2‐ones. Mechanistic experiments indicate that vinyl radical is involved in this reaction and an amidyl‐radical‐initiated radical cascade might be responsible for this transformation. [ABSTRACT FROM AUTHOR]

Peptides hold great promise in proteomics, diagnostics and drug discovery. While natural peptides continue to be of key importance, chemically modified unnatural peptides have been found to show enhanced biological activities and improved therapeutic capabilities compared to their natural counterparts. Therefore, the development of efficient and versatile strategies to enable easy access to unnatural peptides is in high demand. In recent years, palladium-catalyzed direct functionalization of inert C(sp3)–H bonds has emerged as a powerful and straightforward synthetic strategy for late-stage modification of peptides. In this review, we summarize recent progress in this emerging field. For clarity, this review is organized into three sections according to the functionalization of the peptide side-chains at β-, γ-, and δ-positions. [ABSTRACT FROM AUTHOR]

The enantioselective desymmetrizing C−H activation of α‐gem‐dialkyl acyclic amides remains challenging because the availability of four chemically identical unbiased methylene C(sp3)−H bonds and increased rotational freedoms of the acyclic systems add tremendous difficulties for chemo‐ and stereocontrol. We have developed a method for the synthesis of acyclic aliphatic amides with α,β‐contiguous stereogenic centers via PdII‐catalyzed asymmetric arylation of unbiased methylene C(sp3)−H, in good yields and with high levels of enantio‐, chemo‐ and diastereoselectivity (up to >99 % ee and >20:1 d.r.). Successive application of this method enables the sequential arylation of the gem‐dialkyl groups with two different aryl iodides, giving a range of β‐Ar1‐β′‐Ar2‐aliphatic acyclic amides containing three contiguous stereogenic centers with excellent diastereoselectivity. [ABSTRACT FROM AUTHOR]

Herein, we describe an unprecedented cascade reaction to β‐stereogenic γ‐lactams involving Pd(II)‐catalyzed enantioselective aliphatic methylene C(sp3)−H alkenylation–aza‐Wacker cyclization through syn‐aminopalladation. Readily available 3,3′‐substituted BINOLs are used as chiral ligands, providing the corresponding γ‐lactams with broad scope and high enantioselectivities (up to 98 % ee). [ABSTRACT FROM AUTHOR]

A strategy for Pd-catalyzed ortho-C-H silylation of biaryl aldehydes enabled by a transient auxiliary is presented. This protocol provides a broad range of ortho-silylated biaryl aldehydes in good yields. The silyl moiety can be further functionalized under mild conditions, rendering the silylated products useful building blocks. Notably, this protocol also offers an opportunity to establish a platform for expeditious synthesis of structurally diverse axially chiral biaryl aldehydes via sequential atroposelective interannular C-H functionalization/intraanular C-H silylation. [ABSTRACT FROM AUTHOR]

Summary of main observation and conclusion: A Pd(II)‐catalyzed enantioselective intramolecular amidation of both benzylic and unbiased methylene C(sp3)−H bonds for the straightforward synthesis of chiral β‐lactams from aliphatic carboxamides is reported. The combination of 2‐pyridinylisopropyl (PIP) auxiliary with 3,3'‐substituted BINOL ligands is crucial for the enhancement of both reactivity and enantiocontrol of differentiating unbiased methylene C(sp3)−H bonds. The desired chemoselective C—N reductive elimination was achieved by employing 2‐fluoro‐1‐iodo‐4‐nitrobenzene as oxidant. [ABSTRACT FROM AUTHOR]

A simple and ubiquitously present group, free amine, is used as a directing group to synthesize axially chiral biaryl compounds by PdII‐catalyzed atroposelective C−H olefination. A broad range of axially chiral biaryl‐2‐amines can be obtained in good yields with high enantioselectivities (up to 97 % ee). Chiral spiro phosphoric acid (SPA) proved to be an efficient ligand and the loading could be reduced to 1 mol % without erosion of enantiocontrol in gram‐scale synthesis. The resulting axially chiral biaryl‐2‐amines also provide a platform for the synthesis of a set of chiral ligands. [ABSTRACT FROM AUTHOR]