Catalytic Enantioselective Reaction of α‐Phenylthioacetonitriles with Imines Using Chiral Bis(imidazoline)–Palladium Catalysts

The catalytic enantioselective reaction of α‐phenylthioacetonitriles with imines has been developed. The reaction of various imines proceeds in good yields and diastereo‐ and enantioselectivities in the presence of chiral bis(imidazoline)–palladium catalysts. The obtained products can be converted into β‐aminonitrile or β‐aminoamide compounds without loss of enantiopurity.     

Catalytic Enantioselective Reaction of α‐Aminoacetonitriles Using Chiral Bis(imidazoline) Palladium Catalysts

The catalytic enantioselective reaction of diphenylmethylidene‐protected α‐aminoacetonitriles with imines has been developed. Good yields and diastereo‐ and enantioselectivities were observed for the reaction of various imines using chiral bis(imidazoline)/Pd catalysts. The reaction of α‐aminonitriles with di‐tert‐butyl azodicarboxylate afforded chiral α,α‐diaminonitriles in high yields with high enantioselectivities.     

Chiral Bis(imidazolidine)‐Derived NCN Pincer Rh Complex for Catalytic Asymmetric Mannich Reaction of Malononitrile with N‐Boc Imines

Chiral bis(imidazolidine)‐derived NCN–rhodium complexes ([PhBidine‐RhX₂] and [tBu‐PhBidine‐RhX₂]) were prepared by a C?H insertion method, and the structures were unequivocally determined by X‐ray crystallographic analysis. The [tBu‐PhBidine‐Rh(OAc)₂] complex smoothly catalyzed an asymmetric Mannich reaction of malononitrile with N‐Boc imines to give products in up to 94 % ee, which are useful for the synthesis of chiral α‐amino acids.     

Catalytic Enantioselective Reaction of Allenylnitriles with Imines Using Chiral Bis(imidazoline)s Palladium(II) Pincer Complexes

The first highly enantioselective reaction of allenylnitriles with imines has been developed. Excellent yields and enantioselectivities were observed for the reaction with various imines using chiral Phebim‐Pd^II complexes. This process offers a simple and efficient synthetic route for various functionalized α‐vinylidene‐β‐aminonitriles and their derivatives.     

Highly Enantioselective Formation of α‐Allyl‐α‐Arylcyclopentanones via Pd‐Catalysed Decarboxylative Asymmetric Allylic Alkylation

A highly enantioselective Pd‐catalysed decarboxylative asymmetric allylic alkylation of cyclopentanone derived α‐aryl‐β‐keto esters employing the (R,R)‐ANDEN‐phenyl Trost ligand has been developed. The product (S)‐α‐allyl‐α‐arylcyclopentanones were obtained in excellent yields and enantioselectivities (up to >99.9 % ee). This represents one of the most highly enantioselective formations of an all‐carbon quaternary stereogenic center reported to date. This reaction was demonstrated on a 4.0 mmol scale without any deterioration of enantioselectivity and was exploited as the key enantioselective transformation in an asymmetric formal synthesis of the natural product (+)‐tanikolide.     

Highly Enantioselective [3+2] Cycloaddition of Vinylcyclopropane with Nitroalkenes Catalyzed by Palladium(0) with a Chiral Bis(tert‐amine) Ligand

An enantioselective [3+2] cycloaddition of vinyl cyclopropane derived from 1,3‐indanedione with nitroalkenes catalyzed by palladium(0) with a chiral bis(tert‐amine) ligand was developed in high yields with good diastereoselectivities and excellent enantioselectivities. The resulting bis(tert‐amine)–palladium complex proved to be a highly efficient catalyst for this cycloaddition.     

Synthesis and Resolution of Planar–Chiral Ruthenium–Palladium Complexes with ECE′ Pincer Ligands

Feel the pinch! Planar–chiral, cationic, ruthenium–palladium complexes based on η⁶,η¹‐coordinated ECE′ pincer ligands are synthesized as racemic mixtures by reacting ECE′–palladium complexes and [Ru(C₅R₅)(MeCN)₃]⁺ arenophiles (R=H or Me). Chiral resolution of the cationic complexes was achieved by using the chiral counterion [Δ‐TRISPHAT]^?, and solving the X‐ray crystal structure of one diastereoisomer (shown here).

     

Chiral γ‐Lactams by Enantioselective Palladium(0)‐Catalyzed Cyclopropane Functionalizations

Cyclopropanes fused to pyrrolidines are important structural features found in a number of marketed drugs and development candidates. Typically, their synthesis involves the cyclopropanation of a dihydropyrrole precursor. Reported herein is a complementary approach which employs a palladium(0)‐catalyzed C? H functionalization of an achiral cyclopropane to close the pyrrolidine ring in an enantioselective manner. In contrast to aryl–aryl couplings, palladium(0)‐catalyzed C? H functionalizations involving the formation of C(sp³)? C(sp³) bonds of saturated heterocycles are very scarce. The presented strategy yields cyclopropane‐fused γ‐lactams from chloroacetamide substrates. A bulky Taddol phosphonite ligand in combination with adamantane‐1‐carboxylic acid as a cocatalyst provides the γ‐lactams in excellent yields and enantioselectivities.     

Enantioselective Direct Alkynylation of Ketones Catalyzed by Chiral CCN Pincer RhIII Complexes

A direct asymmetric alkynylation of ketones with new chiral CCN Rh catalysts containing N‐heterocyclic carbene and oxazoline hybrid ligands is described. The catalytic reaction of fluoroalkyl‐substituted ketones, ArCOCF₂X (X=F, Cl, H), with aromatic and aliphatic alkynes yielded the corresponding chiral propargyl alcohols with high enantioselectivity. Control and kinetic experiments suggested a bis(alkynyl) Rh intermediate as the active species for the C?C bond‐forming step.     

Cyanoalkylation: Alkylnitriles in Catalytic CC Bond‐Forming Reactions

Alkylnitriles are one of the most ubiquitous nitrogen‐containing chemicals and are widely employed in reactions which result in nitrile‐group conversion into other functionalities. Nevertheless, their use as carbon pronucleophiles in carbon–carbon bond‐forming reactions has been hampered by difficulties associated mainly with the catalytic generation of active species, that is, α‐cyano carbanions or metalated nitriles. Recent investigations have addressed this challenge and have resulted in different modes of alkylnitrile activation. This review illustrates these findings, which have set the foundation for the development of practical and conceptually new catalytic, direct cyanoalkylation methodologies.     

Palladium(II)‐Catalyzed Enantioselective Azidation of Unactivated Alkenes

The first Pd‐catalyzed enantioselective azidation of unactivated alkenes has been established by using readily accessible 1‐azido‐1,2‐benziodoxol‐3(1H)‐one (ABX) as an azidating reagent, which affords a wide variety of structurally diverse 3‐N₃‐substituted piperidines in good yields with excellent enantioselectivity. The reaction features good functional‐group compatibility and mild reaction conditions. Notably, both an electrophilic azidating reagent and the sterically bulky chiral pyridinyl‐oxazoline (Pyox) ligand are crucial to the successful reaction.     

Enantioselective Addition of a 2‐Alkoxycarbonyl‐1,3‐dithiane to Imines Catalyzed by a Bis(guanidino)iminophosphorane Organosuperbase

A chiral bis(guanidino)iminophosphorane catalyzes enantioselective addition reactions of a 1,3‐dithiane derivative as a pronucleophile. The chiral uncharged organosuperbase facilitates the addition of benzyloxycarbonyl‐1,3‐dithiane to aromatic N‐Boc‐protected imines to provide optically active α‐amino‐1,3‐dithiane derivatives, which are valuable versatile building blocks in organic synthesis.     

Access to β‐Lactams by Enantioselective Palladium(0)‐Catalyzed C(sp3)H Alkylation

β‐Lactams are very important structural motifs because of their broad biological activities as well as their propensity to engage in ring‐opening reactions. Transition‐metal‐catalyzed C? H functionalizations have emerged as strategy enabling yet uncommon highly efficient disconnections. In contrast to the significant progress of Pd⁰‐catalyzed C? H functionalization for aryl–aryl couplings, related reactions involving the formation of saturated C(sp³)? C(sp³) bonds are elusive. Reported here is an asymmetric C? H functionalization approach to β‐lactams using readily accessible chloroacetamide substrates. Important aspects of this transformation are challenging C(sp³)? C(sp³) and strain‐building reductive eliminations to for the four‐membered ring. In general, the β‐lactams are formed in excellent yields and enantioselectivities using a bulky taddol phosphoramidite ligand in combination with adamantyl carboxylic acid as cocatalyst.