C2-symmetric bissulfoximines as ligands in copper-catalyzed enantioselective Diels-Alder reactions

[reaction: see text] Bissulfoximines have been used as chiral ligands in copper-catalyzed enantioselective Diels-Alder reactions between acryloyl-2-oxazolidinones and cyclopentadiene. After optimizing the ligand structure, the metal source, the counterions, and the solvent, products with up to 93% ee have been obtained.     

C1-symmetric versus C2-symmetric ligands in enantioselective copper-bis(oxazoline)-catalyzed cyclopropanation reactions

A thorough experimental and theoretical study of the enantioselective cyclopropanation of alkenes catalyzed by chiral bis(oxazoline)- and azabis(oxazoline)-copper complexes, which comprise a new family of ligands that lack C2 symmetry, has been conducted. Surprisingly high enantioselectivities were observed with some of these ligands, which were rationalized on the basis of molecular modeling studies. The course of the asymmetric induction in connection with ligand symmetry and the implications for supported enantioselective catalysts are discussed.     

Concise and stereocontrolled synthesis of pseudo-C2-symmetric diamino alcohols and triamines for use in HIV protease inhibitors

A new protocol is described for the stereocontrolled synthesis of pseudo-C(2)-symmetric core units of interest as candidates for HIV protease inhibition. Addition of unbranched and branched organolithium reagents to cyanohydrins from l-phenylalaninal and l-isoleucinal, followed by in situ reduction of the intermediate imines and CHT deprotection under MW irradiation, led to 1,3-diamino alcohols 6a and 8a as the major products in satisfactory to good yields. The first preparation of a previously unreported pseudo-C(2)-symmetric triamino derivative was accomplished expeditiously via high-yielding nitro-Mannich addition of the silylnitronate, from 2-phenyl-1-nitroethane, to the PMP imine derived from l-phenylalaninal. Reduction of the nitro group in the moderately unstable nitro diamine adduct, followed by chromatographic separation of the required diastereoisomer and CHT debenzylation under MW irradiation, led to the 2-PMP-protected triamine 19 isolated as a bis(sulfonamide).     

Catalytic enantioselective amination of enolsilanes using C2-symmetric copper(II) complexes as chiral Lewis acids

[formula: see text] [Cu(S,S)-t-Bu-box](OTf)2 (1) catalyzes the enantioselective amination of enolsilanes with azodicarboxylate derivatives. Isomerically pure enolsilanes of aryl ketones, acylpyrroles, and thioesters added to the azo-imide in greater than 95% ee. The use of an alcohol additive was critical to achieving catalyst turnover.     

Novel C 2-symmetric bis-oxazoline ligands

Two novel C ₂-symmetric bis-oxazoline ligands were synthesized and their complexes with Cu(OAc)₂ were studied as catalysts in the enantioselective Henry reaction of 4-nitrobenz-aldehyde with nitromethane giving high yield of nitro aldol with ee up to 40%.     

Catalytic enantioselective synthesis of secondary allylic alcohols from terminal alkynes and aldehydes via 1-alkenylboron reagents

A practical one-pot method has been developed for preparing enantioenriched secondary allylic alcohols starting from terminal alkynes and aldehydes. Hydroboration of terminal alkynes with dicyclohexylborane and subsequent reaction of the resulting alkenylboron reagents with aldehydes in the presence of a catalytic amount (5 mol %) of 3-(3,5-diphenylphenyl)-H(8)-BINOL and excess titanium tetraisopropoxide afforded the corresponding allylic alcohols in high enantioselectivities up to 94% ee.     

A new class of C1-symmetric monosulfoximine ligands for enantioselective hetero Diels-Alder reactions

Quinoline-based C1-symmetric sulfoximines have been used as chiral ligands in copper-catalyzed asymmetric hetero Diels-Alder reactions leading to cycloadducts with up to 96% ee.     

Catalytic enantioselective total synthesis of (+)-torrubiellone C

Silyl-protected (R)-methyl 2-(hydroxymethyl)butanoate was obtained by an enantioselective Ir-catalyzed hydrogenation in high yield and selectivity. Elaboration of this building block via Takai and Stille reactions gave a protected hydroxy polyene chain, which was coupled to a 5-hydroxyphenyl-4-hydroxy-2-pyridone derivative by a modified Horner-Wadsworth-Emmons reaction. Deprotection gave synthetic (+)-torrubiellone C, which led to the assignment of the configuration of the natural product as (R).     

Catalytic enantioselective cyclopropanation of allylic alcohols using recyclable fluorous disulfonamide ligand

Cyclopropanation of allylic alcohols with Et₂Zn and CH₂I₂ in the presence of a catalytic amount of fluorous disulfonamide 3 afforded the corresponding cyclopropylmethanols in 69-96% yield with 49-83% ee. The fluorous ligand 3 was readily recovered from the reaction mixture by the fluorous solid-phase extraction (FSPE) and could be reused without a significant loss of the catalytic activity and enantioselectivity.     

Highly enantioselective aminoacylase-catalyzed transesterification of secondary alcohols

The aminoacylase (N-acyl-l-amino acid amidohydrolase; E.C. 3.5.1.14) from Aspergillus melleus, a readily available inexpensive enzyme, catalyzes the transesterification of a wide range of chiral secondary arylalkanols with essentially absolute stereoselectivity (E>500). Moreover, the productivities obtained with 1-phenylethanol, 1-phenylpropanol, 1-(1-naphthyl)ethanol and 1-(2-naphthyl)ethanol were substantially higher than those in the corresponding lipase-catalyzed transesterifications.     

Enantioselective synthesis of secondary alcohols in the presence of chiral ligands

The synthesis of two S-proline derivatives is described together with their use as chiral ligands for lithium in reactions of n-butyllithium with benzaldehyde to give 1-phenyl-1-pentanol with moderate optical purity. The presence of lithium salts in the reaction mixture causes a decrease in asymmetric induction.     

Highly enantioselective synthesis of beta-amino alcohols

[reaction: see text] N,N-Dialkyl-beta-amino alcohols derived from alpha-amino acids can be rearranged enantiospecifically by using TFAA/Et3N/NaOH to give 1,2-amino alcohols with enantiomeric excess up to 99%.     

Catalytic palladium phosphination: modular synthesis of C1-symmetric biaryl-based diphosphines

A new family of C(1)-symmetric bis(diphenylphosphino)biphenyls have been prepared starting from readily available ortho,ortho'-dihalobiphenyl precursors by a palladium-catalyzed C-P coupling reaction. This process does not require the use of an additional ligand. To date, the synthesis of such diphosphines, by reaction of an intermediate biphenyldiyl dianion with ClPPh(2), mainly afforded the undesired cyclic phosphafluorene derivative. So far, no synthetic pathway has been found to avoid this intramolecular reaction. Herein we report the first general and external-ligand-free palladium-catalyzed phosphination reaction that allows the synthesis of a wide variety of substituted ortho,ortho'-bis(diphenylphosphino)biphenyls. With the aim of illustrating the scope and efficiency of this methodology, we applied it to the establishment of a straightforward access to C(1)-symmetrical analogues of the most powerful ligands used in homogenous catalysis and extended it to more challenging substrates.     

C1 and C2-symmetric carbohydrate phosphorus ligands in asymmetric catalysis

Carbohydrates are increasingly used as starting materials for the synthesis of enantiopure ligands. They contain a considerable number of stereocenters, and compounds with all possible configurational combinations are readily available. This tutorial review focuses on ligands obtained by the introduction of phosphorus functionalities (mainly phosphinite, phosphite or phosphine) into a carbohydrate framework. They are classified according to their structural features. In this review, ligands are organised as C1 ligands with a pyranoside or furanoside structure, and C2 ligands. Particular attention is paid to water soluble ligands prepared from carbohydrates. General methods for the preparation of the ligands are presented in order to show how the backbones can be obtained from simple carbohydrates. The catalytic results obtained in commonly studied processes are presented in tables in order to facilitate the comparison between the ligands. The advantages and limitations of the use of ligands based on carbohydrates are discussed.     

Copper(II)-catalyzed hydrosilylation of ketones using chiral dipyridylphosphane ligands: highly enantioselective synthesis of valuable alcohols

In the presence of PhSiH(3) as the reductant, the combination of enantiomeric dipyridylphosphane ligands and Cu(OAc)(2)·H(2)O, which is an easy-to-handle and inexpensive copper salt, led to a remarkably practical and versatile chiral catalyst system. The stereoselective formation of a selection of synthetically interesting β-, γ- or δ-halo alcohols bearing high degrees of enantiopurity (up to 99.9% enantiomeric excess (ee)) was realized with a substrate-to-ligand molar ratio (S/L) of up to 10,000. The present protocol also allowed the hydrosilylation of a diverse spectrum of alkyl aryl ketones with excellent enantioselectivities (up to 98% ee) and exceedingly high turn-over rates (up to 50,000 S/L molar ratio in 50 min reaction time) in air, under very mild conditions, which offers great opportunities for the preparation of various physiologically active targets. The synthetic utility of the chiral products obtained was highlighted by the efficient conversion of optically enriched β-halo alcohols into the corresponding styrene oxide, β-amino alcohol, and β-azido alcohol, respectively.     

Catalytic enantioselective synthesis of secondary alkylboronate building blocks with and without metals

With or without you: Chiral secondary alkylboronates can now be accessed by highly enantioselective catalytic methods including conjugate addition under metal-free conditions with an NHC catalyst, and also iridium-catalyzed hydrogenation. These methods reinforce the potential of secondary alkylboronates as ideal and universal chiral building blocks for bond formation to sp(3) carbon atoms.     

Catalytic enantioselective addition of diethylzinc to aldehydes using aziridine based chiral ligands

The readily available ferrocenyl substituted aziridinylmethanol 1 (FAM-1) was used as a chiral catalyst in the diethylzinc addition reaction to aromatic and aliphatic aldehydes to give secondary alcohols in high yields and up to 99% enantiomeric excess at room temperature. The catalyst can be recovered and used without losing its activity.     

Catalytic enantioselective addition of organometallic reagents to N-formylimines using monodentate phosphoramidite ligands

The asymmetric synthesis of protected amines via the copper/phosphoramidite-catalyzed addition of organozinc and organoaluminum reagents to N-acylimines, generated in situ from aromatic and aliphatic alpha-amidosulfones, is reported. High yields of optically active N-formyl-protected amines and enantioselectivities up to 99% were obtained. Under the reaction conditions, partial oxidation of the phosphoramidite ligand to the corresponding phosphoric amide was detected. A preliminary study on the origin and the effect on the catalytic addition reaction is presented.