Catalytic Enantioselective Addition of Alkyl Grignard Reagents to Aliphatic Aldehydes

Herein, we report an efficient catalytic system for the enantioselective addition of alkyl Grignard reagents to a broad range of aliphatic aldehydes with good yields and enantioselectivities. Remarkably, the challenging methylmagnesium bromide (MeMgBr) can also be added to a variety of aliphatic aldehydes, providing versatile chiral methyl carbinol units with unprecedented yields and enantioselectivities in a simple one‐pot procedure under mild conditions.     

Second‐Generation N,O‐[2.2]Paracyclophane Ketimine Ligands for the Alkenylzinc Addition to Aliphatic and Aromatic Aldehydes: Scope and Limitations

Second generation N,O‐[2.2]paracyclophane ketimine ligands were investigated for their ability to catalyze the 1,2‐addition of alkenylzinc reagents to aliphatic and aromatic aldehydes with special focus on functionalized substrates. For aliphatic aldehydes, which have always been challenging in this field, remarkably high enantiomeric excesses could be determined (50–95 % ee). However, alkenylzinc reagents bearing heteroatoms proved to be demanding substrates for this system.     

Organocatalytic Highly Enantioselective Conjugate Addition of Aldehydes to Alkylidine Malonates

The first highly enantioselective, direct organocatalytic conjugate addition of unmodified aldehydes to alkylidinemalonates is presented. The reaction gives access to β‐formyl‐substituted malonates and highly functionalized lactones with up to 14:1 dr and generally 94 to >99% ee.     

Second‐Generation Paracyclophane Imine Ligands for the Dialkylzinc Addition to Aldehydes. Optimization of the Branched Side Chain leads to Improvement for Aliphatic Aldehydes

Two novel diastereomeric [2.2]paracyclophane ketimine ligands (S_P,S)‐ 2 and (R_P,S)‐ 2 , which unite a planar chiral element and a central chiral element, were used towards the enantioselective diethylzinc addition onto aliphatic aldehydes. These improved second‐generation ligands, which are stable in air and water and are easy to obtain, showed significant improvements with respect to the ligands that were previously used.     

Highly Efficient Ion‐Tagged Catalyst for the Enantioselective Michael Addition of Aldehydes to Nitroalkenes

The ion‐tagged diphenylprolinol silyl ether 6 very efficiently catalyzes the asymmetric Michael addition of aliphatic aldehydes to nitroalkenes with ee of up to>99.5% at low catalyst loadings (0.25–5 mol%) and using only a slight excess of aldehydes (1.2–2 equiv.). This new organocatalyst can be used with the same outstanding efficiency in a wide variety of solvents and reaction conditions.     

Design of Silica-Supported Dendritic Chiral Catalysts for the Improvement of Enantioselective Addition of Diethylzinc to Benzaldehyde

This article describes an efficient method to design a heterogeneous catalyst for the enantioselective addition of diethylzinc to benzaldehyde. Combining the immobilization of a dendrimer on a silica surface with the introduction of a long alkyl spacer at the periphery of the dendrimer is found to be effective in improving the conversion, selectivity and enantioselectivity.     

Modular Synthesis of Ar‐BINMOL‐Phos for Catalytic Asymmetric Alkynylation of Aromatic Aldehydes with Unexpected Reversal of Enantioselectivity

An interesting group of multifunctional phosphines (Ar‐BINMOL‐Phos; Ar‐BINMOL=1,1′‐binaphthalene‐2‐α‐arylmethanol‐2′‐ol) with multi‐stereogenic centers of axial and sp³‐central chirality has been prepared successfully from a single chiral source through a concise synthetic route, in which the neighbouring lithium‐promoted [1,2]‐Wittig rearrangement proceeding with excellent diastereoselectivity and enantioselectivity is the key process in this approach. Also, in the catalytic alkynylation of aromatic aldehydes with terminal alkynes, the combination of these Ar‐BINMOL‐Phos ligands with dimethylzinc was found to be an effective catalyst system to afford predominantly the S‐configured propargylic alcohols, whereas the additional use of calcium hydride and n‐butyllithium along with the same Ar‐BINMOL‐Phos ligands gave the R‐configured products in high yields and excellent enantioselectivities (up to >99% ee).

     

Robust and Recyclable Self‐Supported Chiral Nickel Catalyst for the Enantioselective Michael Addition

A simple chemical modification of a chiral diamine ligand may produce a robust and recyclable enantioselective catalyst. Metallopolymers based on chiral cyclohexyldiamine‐containing ditopic ligands and nickel(II) complexes have been readily prepared and applied in catalytic enantioselective Michael additions of 1,3‐dicarbonyl compounds to nitroalkenes. High yields and good enantioselectivities have been obtained and the catalytic systems have been recycled up to 11 times without loss of either activity or enantioselectivity at a low catalyst loading of 0.75 mol%. Moreover, the nickel metallopolymers were found to be air‐ and moisture‐stable, which enabled this chemistry to be carried out on the bench without the use of any air‐free techniques and with non‐degassed solvents. Finally, the nature of the catalyst was studied by non‐linear effect experiments, giving a negative non‐linear effect (NLE) as a consequence of an in situ decrease in the ee of the active species consistent with the trapping of homochiral aggregates.

     

手性金属络合物催化剂在不对称合成中的应用

不对称合成是当前有机合成中热门研究领域,利用手性金属络合物催化剂催化不对称硅氢化、烷基化,以烯烃、酮、亚胺、醛等合成手性醇、手性胺、手性酮等具有很好的工业应用前景。本文论述了手性金属络合物催化剂在不对称硅氢化反应及其在二烷基锌对醛的不对称烷基化反应中的应用。     

Enantioselective Total Synthesis of (+)‐Gephyrotoxin 287C

Gephyrotoxin 287C, a bioactive alkaloid bearing a perhydropyrrolo[1,2‐a]quinoline skeleton with five stereocenters, is an attractive target for synthetic organic chemistry. We achieved an enantioselective total synthesis of (+)‐gephyrotoxin 287C, for which the key steps were palladium‐catalyzed asymmetric allylic amination using a chiral diaminophosphine oxide (DIAPHOX) preligand, diastereoselective intramolecular Mannich reaction, and tin tetrachloride‐catalyzed diastereoselective conjugate addition/protonation.

     

A Bifunctional Cinchona Alkaloid‐Squaramide Catalyst for the Highly Enantioselective Conjugate Addition of Thiols to trans‐Chalcones

A chiral squaramide catalysts‐promoted asymmetric sulfa‐Michael conjugated addition of thiols to trans‐chalcones is presented. Moderate to excellent yields and high enantioselectivities (up to 99% ee) were achieved under mild conditions.     

Enantioselective Organocatalytic Addition of Nitroalkanes to Oxindolylideneindolenines for the Construction of Chiral 3,3‐Disubstituted Oxindoles

An enantioselective organocatalytic addition of nitroalkanes to oxindolylideneindolenines in the presence of bifunctional organocatalysts has been established to provide an efficient entry to 3,3‐disubstituted oxindole derivatives in high yields and with excellent enantioselectivities. The transformation has been applied to the preparation of the key intermediate for a formal total synthesis of (+)‐gliocladin C.

     

Asymmetric Epoxidation of Allylic Alcohols Catalyzed by (≡SiO) x Ta(OEt)3-x (Dialkyl Tartrate Diolate): Influence of the Reaction Conditions

Silica-supported chiral tantalum alkoxides are active catalysts for the asymmetric epoxidation of propenol and trans hex-2-en-1ol. The influence of different parameters on their catalytic performance was followed: the impregnation duration by a tartrate (step in their preparation); the nature of the solvent (CH₂Cl₂, pentane, toluene) and of the oxidant (TBHP, CHP, H₂O₂); poisoning effects by water or t-butanol; the reaction temperature and the substrate concentration.     

Highly Active Polymer‐Supported (Salen)Al Catalysts for the Enantioselective Addition of Cyanide to α,β‐Unsaturated Imides

In this contribution, we describe polymer‐supported (R,R)‐(salen)AlCl complexes that were immobilized on poly(norbornene)s and display excellent activities and enantioselectivies as catalysts for the 1,4‐conjugate addition of cyanide to α,β‐unsaturated imides. These supported catalysts could be recycled up to 5 times without compromising catalyst activities or selectivities. Furthermore, the catalyst loadings could be reduced from 10–15 mol%, the common catalyst loadings for non‐supported (salen)Al catalysts, to 5 mol%, a decrease of metal content by 50–66%, without lowering product yields or enantioselectivities. Kinetic studies indicated that the polymer‐supported catalysts are significantly more active than their corresponding unsupported analogues, which makes this catalyst system key to a successful implementation of this catalytic transformation into the fine chemical and pharmaceutical industries.     

A Chiral Bipyridyl Alcohol for Catalytic Enantioselective Nozaki–Hiyama–Kishi Allylation of Aldehydes and Ketones

A class of bipyridyl alcohol ligands has been developed. A catalyst synthesized using a chromium(II)‐ligand promotes the enantioselective Nozaki–Hiyama–Kishi (NHK) allylation of aldehydes and ketones with allylic halides. The allylation of various aromatic, α,β‐unsaturated, and aliphatic aldehydes and ketones produces the desired homoallylic alcohols in satisfactory yields (up to 98%) and high enantioselectivities (up to 99% ee). The present method can be applied widely and affords an efficient means of obtaining chiral homoallylic alcohols.

     

Relay Catalysis: Enantioselective Synthesis of Cyclic Benzo‐Fused Homoallylic Alcohols by Chiral Brønsted Acid‐Catalyzed Allylboration/Ring Closing Metathesis

Six‐ and seven‐membered benzo‐fused cyclic homoallylic alcohols can be readily synthesized by a tandem chiral Brønsted acid‐catalyzed allyl (crotyl)boration/ring closing metathesis sequence performed under orthogonal relay catalysis conditions. Excellent enantio‐ and diastereoselectivities are obtained in most of the cases. In addition, the parent crotylboration/RCM process is also described. The required substrates, ortho‐vinylbenzaldehydes, are readily available in one step from commercially available starting materials. Both catalysts and reactants are also available from commercial suppliers. The reaction shows broad functional group compatibility and is also suitable for heteroaromatic substrates. Substitution at any position of the aromatic ring is tolerated; however, substitution at position 6 results in a substantial drop in enantioselectivity.     

手性BINOL磷酸催化剂在不对称转化中的应用

3,3＇-位基团取代手性BINOL磷酸在不对称催化反应中具有较强的催化活性。其原因在于：（1）手性BINOL磷酸具有较强的（P=O）Lewis碱和较强的（P-OH）Lewis酸,可以有效通过与催化底物之间形成氢键,激活反应体系;（2）在手性BINOL磷酸的3,3＇-位上引入阻位基团,建立有效的手性环境,可以成功地诱导不对称转化。本文例举了通过氢键相互作用,手性BINOL磷酸催化剂成功地诱导不对称催化反应。