Spiro[4,4]‐1,6‐nonadiene‐Based Phosphine–Oxazoline Ligands for Iridium‐Catalyzed Enantioselective Hydrogenation of Ketimines

From imines to amines through catalysis by Ir^I complexes of a new type of P,N ligand (see scheme): This reaction affords the corresponding optically active amines with up to 98 % ee and has also been used with perfect stereoselectivity in the asymmetric synthesis of sertraline ( 1 ), an important antidepressant chiral drug.

     

Highly Modular C1‐Symmetric Chiral (P,N) Ligands with a Stereolabile P Center: Experimental and Theoretical Studies

An improved synthesis of a novel class of bidentate (P,N) ligands is presented, the structures of which are characterized by three distinct elements of chirality. The stereoselective installation of the elements of central chirality (at the benzylic carbon and the phosphorus atom) depends on the size of the phosphorus substituent. Thermal inversion of the phosphorus center has been studied experimentally and further correlated by DFT calculations. The potential of these ligands and the role of the phosphorus atom in the asymmetric α‐arylation of aldehydes (Pd) and hydrogenation of allylic alcohols (Ir) have also been investigated.     

Chiral Bifunctional Phosphine‐Carboxylate Ligands for Palladium(0)‐Catalyzed Enantioselective C−H Arylation

Previous enantioselective Pd⁰‐catalyzed C?H activation reactions proceeding via the concerted metalation‐deprotonation mechanism employed either a chiral ancillary ligand, a chiral base, or a bimolecular mixture thereof. This study describes the development of new chiral bifunctional ligands based on a binaphthyl scaffold which incorporates both a phosphine and a carboxylic acid moiety. The optimal ligand provided high yields and enantioselectivities for a desymmetrizing C(sp²)?H arylation leading to 5,6‐dihydrophenanthridines, whereas the corresponding monofunctional ligands showed low enantioselectivities. The bifunctional system proved applicable to a range of substituted dihydrophenanthridines, and allowed the parallel kinetic resolution of racemic substrates.     

Adaptative Biaryl Phosphite–Oxazole and Phosphite–Thiazole Ligands for Asymmetric Ir‐Catalyzed Hydrogenation of Alkenes

A library of readily available phosphite–oxazole/thiazole ligands ( L1 a – g – L7 a – g ) was applied in the Ir‐catalyzed asymmetric hydrogenation of several largely unfunctionalized E‐ and Z‐trisubstituted and 1,1‐disubstituted terminal alkenes. The ability of the catalysts to transfer chiral information to the product could be tuned by choosing suitable ligand components (bridge length, the substituents in the heterocyclic ring and the alkyl backbone chain, the configuration of the ligand backbone, and the substituents/configurations in the biaryl phosphite moiety), so that enantioselectivities could be maximized for each substrate as required. Enantioselectivities were therefore excellent (enantiomeric excess (ee) values up to >99 %) for a wide range of E‐ and Z‐trisubstituted and 1,1‐disubstituted terminal alkenes. The biaryl phosphite moiety was a very advantageous ligand component in terms of substrate versatility.     

Chiral N,N Ligands Enabling Palladium‐Catalyzed Enantioselective Intramolecular Heck–Matsuda Carbonylation Reactions by Sequential Migratory and CO Insertions

Unprecedented enantioselective intramolecular Heck carbonylation reactions of arenediazonium salts were enabled by a chiral N,N ligand. This reaction constitutes the first enantioselective Heck carbonylation that proceeds through migratory insertion followed by CO insertion. The enantioenriched functionalized dihydrobenzofurans were obtained in good to high yields and enantiomeric ratios of up to 98:2 under mild and operationally simple reaction conditions.     

A Zwitterionic Phosphonio‐1, 2, 4‐Diazaphospholide and Neutral 1, 2, 4‐Diazaphosphole — A Comparative Study of Molecular Structures and Co‐ordination Properties

The bis‐phosphonio‐1, 2, 4‐diazaphospholide salt ( 1 [Cl]) reacts with complex boron hydrides under selective extrusion of one PPh₃ moiety to give borane adducts of a novel zwitterionic phosphonio‐1, 2, 4‐diazaphospholide. Both the Et₃B adduct 2b and the free zwitterionic heterocycle 3 , which was liberated by further reaction of 2b with NEt₃, were characterized by spectroscopic data and 2b , as well, by a single crystal X‐ray diffraction study. The comparison of the structural data with those of a neutral 1, 2, 4‐diazaphosphole and a lithium‐1, 2, 4‐diazaphospholide which was formed by deprotonation of the parent 1, 2, 4‐diazaphosphole 4a discloses trends in endocyclic bonding distances which can be rationalized in terms of a charge dependent shift in the π‐electron distribution. First studies of the co‐ordination properties reveal for both 2b and 4a a marked preference to bind two M(CO)₅‐fragments (M = Cr, W) via the lone‐pairs of the phosphorus and one nitrogen atom; mononuclear complexes with P‐co‐ordinated heterocycles are formed as intermediates. A single crystal X‐ray diffraction study of the dinuclear complex [Cr₂(CO)₁₀(μ₂‐C₂H₃N₂P‐κP, κN)] ( 10a ) together with spectroscopic studies (including ¹⁸³W NMR studies of tungsten complexes) suggests that M→L back donation is more efficient for P‐ than for N‐bound metal fragments. No evidence for π‐co‐ordination of the 1, 2, 4‐diazaphosphole ring to a Cr(CO)₃ fragment was obtained.     

1H NMR assignment of oligomeric grafts of maleic anhydride‐grafted polyolefin

The ¹ H NMR assignment of oligomeric grafts of maleic anhydride (MA)‐grafted polyolefin (PO), MA‐g‐PO hereafter, was experimentally demonstrated for the first time using NMR spectroscopy. ¹³ C DEPT, ¹ H‐¹ H DQF‐COSY, and ¹ H T₂‐edited spectroscopy of MA‐g‐PO proved that peaks of the intermediate methine protons of succinic anhydride oligomeric grafts, which are nearly tetrameric, are observed at 2.5–3.5 ppm and show broadening. Copyright © 2012 John Wiley & Sons, Ltd.     

Modulation of Multifunctional N,O,P Ligands for Enantioselective Copper‐Catalyzed Conjugate Addition of Diethylzinc and Trapping of the Zinc Enolate

In this work, we have successfully synthesized a new family of chiral Schiff base–phosphine ligands derived from chiral binaphthol (BINOL) and chiral primary amine. The controllable synthesis of a novel hexadentate and tetradentate N,O,P ligand that contains both axial and sp³‐central chirality from axial BINOL and sp³‐central primary amine led to the establishment of an efficient multifunctional N,O,P ligand for copper‐catalyzed conjugate addition of an organozinc reagent. In the asymmetric conjugate reaction of organozinc reagents to enones, the polymer‐like bimetallic multinuclear Cu? Zn complex constructed in situ was found to be substrate‐selective and a highly excellent catalyst for diethylzinc reagents in terms of enantioselectivity (up to >99 % ee). More importantly, the chirality matching between different chiral sources, C₂‐axial binaphthol and sp³‐central chiral phosphine, was crucial to the enantioselective induction in this reaction. The experimental results indicated that our chiral ligand (R,S,S)‐ L1 ‐ and (R,S)‐ L4 ‐based bimetallic complex catalyst system exhibited the highest catalytic performance to date in terms of enantioselectivity and conversion even in the presence of 0.005 mol % of catalyst (S/C=20 000, turnover number (TON)=17 600). We also studied the tandem silylation or acylation of enantiomerically enriched zinc enolates that formed in situ from copper‐ L4 ‐complex‐catalyzed conjugate addition, which resulted in the high‐yield synthesis of chiral silyl enol ethers and enoacetates, respectively. Furthermore, the specialized structure of the present multifunctional N,O,P ligand L1 or L4 , and the corresponding mechanistic study of the copper catalyst system were investigated by ³¹P NMR spectroscopy, circular dichroism (CD), and UV/Vis absorption.     

A Chiral Nitrogen Ligand for Enantioselective,Iridium‐Catalyzed Silylation of Aromatic C−H Bonds

Iridium catalysts containing dative nitrogen ligands are highly active for the borylation and silylation of C−H bonds, but chiral analogs of these catalysts for enantioselective silylation reactions have not been developed. We report a new chiral pyridinyloxazoline ligand for enantioselective, intramolecular silylation of symmetrical diarylmethoxy diethylsilanes. Regioselective and enantioselective silylation of unsymmetrical substrates was also achieved in the presence of this newly developed system. Preliminary mechanistic studies imply that C−H bond cleavage is irreversible, but not the rate‐determining step.     

A Mild Dihydrobenzooxaphosphole Oxazoline/Iridium Catalytic System for Asymmetric Hydrogenation of Unfunctionalized Dialins

Air‐stable P‐chiral dihydrobenzooxaphosphole oxazoline ligands were designed and synthesized. When they were used in the iridium‐catalyzed asymmetric hydrogenation of unfunctionalized 1‐aryl‐3,4‐dihydronaphthalenes under one atmosphere pressure of H₂, up to 99:1 e.r. was obtained. High enantioselectivities were also observed in the reduction of the exocyclic imine derivatives of 1‐tetralones.     

A New Modular Phosphite‐Pyridine Ligand Library for Asymmetric Pd‐Catalyzed Allylic Substitution Reactions: A Study of the Key Pd‐π‐Allyl Intermediates

A library of phosphite‐pyridine ligands L1 – L12 a – g has been successfully applied for the first time in the Pd‐catalyzed allylic substitution reactions of several di‐ and trisubstituted substrates by using a wide range of C, N and O nucleophiles, among which are the little studied α‐substituted malonates, β‐diketones, and alkyl alcohols. The highly modular nature of this ligand library enables the substituents/configuration at the ligand backbone, and the substituents/configurations at the biaryl phosphite moiety to be easily and systematically varied. We found that the introduction of an enantiopure biaryl phosphite moiety played an essential role in increasing the versatility of the Pd‐catalytic systems. Enantioselectivities were therefore high for several hindered and unhindered di‐ and trisubstituted substrates by using a wide range of C, N and O nucleophiles. Of particular note were the high enantioselectivities (up to>99 % ee) and high activities obtained for the trisubstituted substrates S6 and S7 , which compare favorably with the best that have been reported in the literature. We have also extended the use of these new catalytic systems in alternative environmentally friendly solvents such as propylene carbonate and ionic liquids. Studies on the Pd‐π‐allyl intermediates provide a deeper understanding of the effect of ligand parameters on the origin of enantioselectivity.     

A New Class of Modular P,N‐Ligand Library for Asymmetric Pd‐Catalyzed Allylic Substitution Reactions: A Study of the Key Pd–π‐Allyl Intermediates

A new class of modular P,N‐ligand library has been synthesized and screened in the Pd‐catalyzed allylic substitution reactions of several substrate types. These series of ligands can be prepared efficiently from easily accessible hydroxyl–oxazole/thiazole derivatives. Their modular nature enables the bridge length, the substituents at the heterocyclic ring and in the alkyl backbone chain, the configuration of the ligand backbone, and the substituents/configurations in the biaryl phosphite moiety to be easily and systematically varied. By carefully selecting the ligand components, therefore, high regio‐ and enantioselectivities (ee values up to 96 %) and good activities are achieved in a broad range of mono‐, di‐, and trisubstituted linear hindered and unhindered substrates and cyclic substrates. The NMR spectroscopic and DFT studies on the Pd–π‐allyl intermediates provide a deeper understanding of the effect of ligand parameters on the origin of enantioselectivity.     

Rhodium‐catalyzed Asymmetric Hydrogenation of α‐Dehydroamino Ketones: A General Approach to Chiral α‐amino Ketones

Rhodium/DuanPhos‐catalyzed asymmetric hydrogenation of aliphatic α‐dehydroamino ketones has been achieved and afforded chiral α‐amino ketones in high yields and excellent enantioselectives (up to 99 % ee), which could be reduced further to chiral β‐amino alcohols by LiAlH(tBuO)₃ with good yields_. This protocol provides a readily accessible route for the synthesis of chiral α‐amino ketones and chiral β‐amino alcohols.