Atroposelective synthesis of axially chiral biaryl compounds

A rotationally hindered and thus stereogenic biaryl axis is the structurally and stereochemically decisive element of a steadily growing number of natural products, chiral auxiliaries, and catalysts. Thus, it is not surprising that significant advances have been made in the asymmetric synthesis of axially chiral biaryl compounds over the past decade. In addition to the classic approach (direct stereoselective aryl-aryl coupling), innovative concepts have been developed in which the asymmetric information is introduced into a preformed, but achiral-that is, symmetric or configurationally labile-biaryl compound, or in which an aryl--C single bond is stereoselectively transformed into an axis. This Review classifies these strategies according to their underlying concepts and critically evaluates their scope and limitations with reference to selected model reactions and applications. Furthermore, the preconditions required for the existence of axial chirality in biaryl compounds are discussed.     

Asymmetric synthesis of an axially chiral antimitotic biaryl via an atropo-enantioselective Suzuki cross-coupling

A catalytic asymmetric synthesis of the axially chiral bridged biaryl (-)-2, a structural analogue of natural (-)-rhazinilam possessing original antimitotic properties, is described. The key step is an intermolecular asymmetric Suzuki coupling, furnishing the nonbridged biaryl (-)-6, precursor of (-)-2, with up to 40% ee using binaphthyl ligand 7a. Various known or new binaphthyl and ferrocenyl phosphines as well as phosphetanes were screened as ligands in this reaction, the conditions of which were optimized. The comparison with another Suzuki coupling system showed that 7a is the most versatile ligand described to date for this type of transformation. This work gives the first application of the asymmetric Suzuki coupling to a biologically relevant target.     

手性联苯类化合物的制备

手性联苯化合物在有机合成和天然产物化学中都有相当重要的地位,本文论述了近年来得到手性联苯类化合物的一些方法。     

Atropo-enantioselective reduction of configurationally unstable biaryl lactones with BINAL-H

The atropo-enantioselective reduction of configurationally unstable biaryl lactones with BINAL-H yields axially chiral biaryl alcohols in high enantiomeric ratios of up to 94:6 (er >99.5:0.5 after one crystallization step). Within this two-step reduction process the stereochemically deciding step is the first attack on the lactones and not the reduction of the likewise configurationally unstable biaryl lactol/hydroxy aldehyde intermediates, as evident from the non-stereoselective reduction of the latter under the same conditions.     

Stereoselective tricarbonylchromium migration reactions in axially chiral biaryl chromium complexes

The tricarbonylchromium group in thermodynamically unstable biaryl chromium complexes with a coordinating heteroatom at the side chain stereoselectively migrated to the other arene face to release the steric repulsion.     

Catalytic enantioselective synthesis of axially chiral allenes

The conventional procedures for preparing optically active axially chiral allenes generally require stoichiometric chiral sources as either substrates or reagents. On the other hand, examples of catalytic asymmetric synthesis of axially chiral allenes are rare and it is a relatively underdeveloped area in synthetic organic chemistry. In this review article, various methods for preparing enantiomerically enriched axially chiral allenes using substoichiometric chiral sources are surveyed. Some reactions with stoichiometric but recoverable chiral sources are also mentioned. Most of the asymmetric reactions in these categories are transition-metal-catalyzed reactions, and there are a few examples of organocatalytic reactions. In addition, some enzymatic/microbial systems are also known.     

Atropo-enantioselective synthesis of a C3-symmetric tripodal ligand with three axially chiral biaryl subunits

In contrast to the numerous successful applications of C₂-symmetric biaryls as powerful tools for asymmetric synthesis, there have so far been only few reports on combinations of C₃-symmetry with axial chirality. We present here the first enantioselective synthesis of a novel family of tripodal ligands containing three axially chiral biaryl subunits in an (M,M,M)- or, optionally, (P,P,P)-configured form. The incorporation of a PCl₂- and a TiCl-fragment into the central cavity was achieved.     

Catalytic enantioselective conjugate reduction of lactones and lactams

A dramatic acceleration of the enantioselective copper-catalyzed conjugate reduction of alpha,beta-unsaturated lactones, lactams, and esters is reported upon addition of alcohol additives. Good to excellent yields and enantioselectivities were realized using a catalyst generated in situ from CuCl(2).H(2)O, t-BuONa, p-tol-BINAP, and PMHS, and this methodology was applied to the synthesis of (-)-Paroxetine.     

Catalytic asymmetric synthesis of axially chiral o-iodoanilides by phase-transfer catalyzed alkylations

Catalytic asymmetric synthesis of axially chiral o-iodoacrylanilides and N-allyl-o-iodoanilides as useful chiral building blocks was achieved via chiral quaternary ammonium salt-catalyzed N-alkylations under phase-transfer conditions. The transition-state structure for the present reaction is discussed on the basis of the X-ray crystal structure of ammonium anilide.     

Catalytic reduction of aromatic polynitro compounds

The liquid-phase catalytic hydrogenation of 3,5-dinitrophenyl phenyl ether to give 3,5-diaminophenyl phenyl ether in the presence of Group VIII metals as catalysts has been investigated. The main kinetic characteristics of the process have been established. The reduction occursvia the formation of 5-amino-3-nitrophenyl phenyl ether. In terms of their activity, the catalysts studied can be arranged in the following sequence: 1% Pd/Sibunit> 2 % Pd/C > Lindlare Pd > 5% Ru/Sibunit > Raney Ni. The selectivity of the process with respect to intermediate 5-amino-3-nitrophenyl phenyl ether depends on the relative adsorption abilities of mono- and dinitro compounds. A promoting effect of water during hydrogenation of 3,5-dinitrophenyl phenyl ether in isopropanol or 1,4-dioxane has been noted. Catalytic synthesis of 3,5-diaminophenyl phenyl ether has been carried out for the first time.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1716–1719, September, 1995.     

Advances in circularly polarized luminescent materials based on axially chiral compounds

Circularly polarized (CP) light, as a special form of polarized light, demonstrates potential application prospects in future displays and optoelectronic technologies. Circularly polarized luminescence (CPL) from chiral chromophores is an ideal method to directly generate CP light, but how to design efficient emitters is always a perplexing problem. Among various chiral materials, CPL materials with axial chirality can provide us with clear structural parameters and information to further explore the structure-activity relationship. Herein, we systematically summarize the development status of axially chiral compounds with CPL properties from two aspects of photoluminescence and electroluminescence, covering metal complexes, polymers, supramolecular assemblies, simple organic molecules, and liquid crystals systems. In addition, we initially explore the relationship between CPL performance and axially chiral configuration, and the current challenges and opportunities in this vibrant field are also discussed.     

Efficient synthesis of biaryl lactones by domino retro-Michael-aldol-lactonization reactions

Biaryl lactones were prepared by novel domino retro-Michael-aldol-lactonization reactions of 2,3-dihydropyrans.     

Asymmetric synthesis of axially chiral biaryl diphosphine ligands by rhodium-catalyzed enantioselective intramolecular double [2 + 2 + 2] cycloaddition

The concise synthesis of axially chiral biaryl diphosphine ligands by the rhodium-catalyzed intramolecular [2 + 2 + 2] cycloaddition of hexayne diphosphine oxides has been achieved. These new chiral diphosphine ligands could be employed as a ligand for the rhodium-catalyzed asymmetric catalyses.     

Diastereoselective photocycloaddition of axially chiral monothiosuccinimides to 1,1-diphenylethylene

Photolysis of axially chiral monothiosuccinimides in the presence of diphenylethylene gave spirothietanes effectively, where the cycloaddition took place diastereoselectively by way of the steric effect of the ortho-substituent on the phenyl ring.     

Murrastifoline-F: first total synthesis, atropo-enantiomer resolution, and stereoanalysis of an axially chiral N,C-coupled biaryl alkaloid.

The first total synthesis of the Murraya alkaloid murrastifoline-F (3), an unsymmetric, N,C-bonded heterobiarylic biscarbazole, is described. Starting from the likewise naturally occurring-but here synthetically prepared-"monomer" murrayafoline-A (6), lead tetraacetate-mediated oxidative non-phenolic biaryl coupling gives 3 as the main regioisomer. The existence of this natural product as a pair of stable atropo-enantiomers was demonstrated analytically through LC-CD investigations. Preparatively, the racemate resolution succeeded by O-demethylation, derivatization with Mosher's reagent, and chromatographic separation of the resulting diastereomers. The absolute configurations of the atropisomers were assigned by CD spectroscopy in combination with quantum chemical CD calculations at the stage of the alkaloid 3 and by ROESY experiments of the diastereomeric Mosher derivatives. In the root extract of the curry leaf plant Murraya koenigii (Rutaceae), murrastifoline-F (3) was found to exist as a 56:44 mixture in favor of the M-enantiomer, by LC-CD coupling.     

Asymmetric synthesis of N–N axially chiral compounds via organocatalytic atroposelective N-acylation

Compared with the well-developed C–C and C–N axial chirality, the asymmetric synthesis of N–N axial chirality remains elusive and challenging. Herein we report the first atroposelective N-acylation reaction of quinazolinone type benzamides with cinnamic anhydrides for the direct catalytic synthesis of optically active atropisomeric quinazolinone derivatives. This reaction features mild conditions and a broad substrate scope and produces N–N axially chiral compounds with high yields and very good enantioselectivities. Besides, the synthetic utility of the protocol was proved by a large scale reaction, transformation of the product and the utilization of the product as an acylation kinetic resolution reagent. Moreover, DFT calculations provide convincing evidence for the interpretation of stereoselection.

A highly efficient atroposelective N-acylation reaction of quinazolinone type benzamides with cinnamic anhydrides for the direct catalytic synthesis of optically active atropisomeric quinazolinone derivatives was developed.     

Catalytic asymmetric borane reduction of prochiral ketones using chiral camphor-derived mercapto-alcohols

Easily available D-(+)-camphor-derived chiral mercapto-alcohols 2 and 3 were employed for catalytic asymmetric borane reduction of aromatic ketones. Moderate enantioselectivities with e.e. 20.2-72.1% were obtained with 10 mol% catalyst. Opposite asymmetric induction was achieved when mercapto-alcohols 2 and 3 were used.     

Nondynamic kinetic resolution of configurationally stable biaryl lactones by reduction with oxazaborolidine-activated borane: AM1 studies and experimental verification

The complete mechanistic course of the atroposelective ring opening of a lactone-bridged biaryl, dinaphth[2,1-c:1',2'-e]oxepin-3-(5H)-one (3), with a chiral oxazaborolidine-BH3 complex was calculated using the semiempirical AM1 method. The first hydride transfer to the activated carbonyl function of the adduct complexes was elaborated to be the selectivity-determining step in the postulated five-step mechanism. The calculated enantioselectivity is in good accordance with the experimental results, so that related calculations were performed on the atroposelective ring opening of a sterically strongly hindered and therefore also configurationally stable six-membered biaryl lactone, 1,3-di-tert-butyl-6H-benzo[b]naphtho[1,2-d]pyran-6-one (6f). These calculations predicted a highly (M)-selective reduction of 6f (kM/kP = 358 at -78 degrees C), which, after the smooth preparation of 6f by intramolecular biaryl coupling in high yields, was fully confirmed experimentally (kM/kP > 200 at -78 degrees C). Isolation of the intermediate hydroxy aldehyde (M)-14 at the beginning of the reaction with the same enantiomeric excess as found for the corresponding alcohol (M)-7f conclusively showed the first hydride transfer step to determine the selectivity of this process. The good agreement of computationally predicted and experimentally confirmed values proves the suitability of the AM1 method for mechanistic studies on even such complex reactions and opens a most efficient overall synthesis of sterically highly hindered biaryls, in excellent chemical (for the ring closure) and optical (for the ring cleavage) yields and for any desired axial configuration.