Asymmetric allylic alkylation of β‐ketoesters with allylic alcohols catalyzed by Ni(cod)2/(S)‐H8‐BINAP was found to be a superior synthetic protocol for constructing quaternary chiral centers at the ...α‐position of β‐ketoesters. The reaction proceeded in high yield and with high enantioselectivity using various β‐ketoesters and allylic alcohols, without any additional activators. The versatility of this methodology for accessing useful and enantioenriched products was demonstrated.
No activation necessary: A nickel/chiral diphosphine (L) system effectively catalyzed the asymmetric allylic alkylation of β‐ketoesters to deliver quaternary chiral centers at the α position of the β‐ketoesters. The present system is highly advantageous in that it requires no activator for either the nucleophiles or the allylic alcohols.
A copper‐catalyzed asymmetric 3+2 cycloaddition of 3‐trimethylsilylpropargylic esters with either β‐naphthols or electron‐rich phenols has been realized and proceeds by a desilylation‐activated ...process. Under the catalysis of Cu(OAc)2⋅H2O in combination with a structurally optimized ketimine P,N,N‐ligand, a wide range of optically active 1,2‐dihydronaphtho2,1‐bfurans or 2,3‐dihydrobenzofurans were obtained in good yields and with high enantioselectivities (up to 96 % ee). This represents the first desilylation‐activated catalytic asymmetric propargylic transformation.
Cu on active duty: The highly enantioselective title reaction of 3‐trimethylsilylpropargylic acetates has been realized on the basis of a desilylation‐activated strategy. With the support of a finely modified ketimine P,N,N‐ligand, the reaction gave rise to either chiral 1,2‐dihydronaphtho‐ or benzofurans in good yields and with up to 96 % ee.
The first asymmetric PdII‐catalyzed aminofluorination of unactivated alkenes using chiral quinoline‐oxazolines (Quox) as ligands has been developed. This reaction provides easy access to a wide array ...of enantiomerically enriched β‐fluoropiperidines in good yields and with excellent enantioselectivity. Notably, Et4NF⋅3 HF as a readily accessible nucleophilic fluoride source was found to play an essential role in the enantioselective control, and CsOCF3 also acts a key additive to improve the excellent ee value of products.
An asymmetric PdII‐catalyzed aminofluorination of unactivated alkenes using chiral quinoline‐oxazolines (Quox) as ligands provides easy access to an array of enantiomerically enriched β‐fluoropiperidines in good yields and with excellent enantioselectivity. Et4NF⋅3 HF plays an essential role in the enantioselective control, and CsOCF3 as an additive impedes ArIF2‐promoted aminofluorination of alkenes.
All‐carbon quaternary stereocenters have posed significant challenges in the synthesis of complex natural products. These important structural motifs have inspired the development of broadly ...applicable palladium‐catalyzed asymmetric allylic alkylation reactions of unstabilized non‐biased enolates for the synthesis of enantioenriched α‐quaternary products. This microreview outlines key considerations in the application of palladium‐catalyzed asymmetric allylic alkylation reactions and presents recent total syntheses of complex natural products that have employed these powerful transformations for the direct, catalytic, enantioselective construction of all‐carbon quaternary stereocenters.
Pd‐catalyzed asymmetric allylic alkylation reactions are powerful transformations for the direct construction of all‐carbon quaternary stereocenters. A variety of chiral building blocks can be prepared by this approach and these key intermediates have enabled the enantioselective synthesis of complex natural products. Recent advances in reaction methodology and total synthesis are discussed.
Asymmetric catalysis with transition-metal complexes is the basis for a vast array of stereoselective transformations and has changed the face of modern synthetic chemistry. Key to this success has ...been the design of chiral ligands to control the regio-, diastereo-, and enantioselectivity. Phosphoramidites have emerged as a highly versatile and readily accessible class of chiral ligands. Their modular structure enables the formation of ligand libraries and easy fine-tuning for a specific catalytic reaction. Phosphoramidites frequently show exceptional levels of stereocontrol, and their monodentate nature is essential in combinatorial catalysis, where a ligand-mixture approach is used. In this Review, recent developments in asymmetric catalysis with phosphoramidites used as ligands are discussed, with a focus on the formation of carbon-carbon and carbon-heteroatom bonds.
The highly efficient and direct asymmetric reductive amination of arylacetones catalyzed by an iridium complex for the preparation of enantiomerically pure β‐arylamines is described. The monodentate ...phosphoramidite ligand exhibits superb reactivity (TONs of up to 20 000) and enantioselectivity (up to 99 % ee). Additives played important roles in this reductive coupling reaction.
Asymmetric reductive coupling of a ketone and an amine is a straightforward and atom‐economic approach for preparing optically enriched amines. The highly efficient and direct asymmetric reductive amination of arylacetones, catalyzed by an iridium complex, supplies enantiomerically pure β‐arylamines. The new phosphoramidite ligands reported show superb reactivity and enantioselectivity in this reductive coupling. M.S.=molecular sieves, TFA=trifluoroacetic acid.
A novel alkyl functionalization of unactivated alkyl quinolines has been developed combining InCl3 activation with organocatalytic activation of α,β‐unsaturated aldehydes in a synergistic fashion. ...The reaction proceeds in a highly stereoselective manner as a sequence involving two consecutive synergistic catalytic cycles (Lewis acid‐ and iminium ion‐catalyzed) and requires neither pre‐activated alkyl quinoline substrates with electron‐withdrawing substituents nor highly activated electrophiles. The reaction provides selectively double‐ or mono‐addition products in good yields and high to excellent stereoselectivities. Furthermore, based on spectroscopic and labelling experiments, the mechanisms for the reactions are discussed.
A fruitful partnership: InCl3 activation of unactivated alkyl quinolines has been combined with organocatalytic activation of α,β‐unsaturated aldehydes. The reaction involves two consecutive synergistic catalytic cycles and provides selectively double‐ or mono‐addition products in good yields and high to excellent stereoselectivities. Based on spectroscopic and labeling experiments, the reaction mechanisms are discussed.
A catalytic asymmetric 3+2 cycloaddition reaction of chiral palladium-containing N(1) -1,3-dipoles with methyleneindolinones has been successfully developed. The reaction allows an efficient ...construction of 3,3'-pyrrolinyl spirooxindoles with high yields and excellent stereoselectivities (up to 93 % yield, 19:1 d.r. and >99 % ee). A synthetic application of this methodology is demonstrated and a stereocontrol mechanism is proposed.
Nickel-catalyzed reductive cross-coupling reactions have emerged as powerful methods to join two electrophiles. These reactions have proven particularly useful for the coupling of sec-alkyl ...electrophiles to form stereogenic centers; however, the development of enantioselective variants remains challenging. In this Perspective, we summarize the progress that has been made toward Ni-catalyzed enantioselective reductive cross-coupling reactions.
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