Axially dissymmetric binaphthyldiimine chiral salen-type ligands for copper-catalyzed asymmetric aziridination

Axially dissymmetric chiral salen-type ligands 1–4 and 7 were prepared from the reaction of (R)-(+)-1,1′-binaphthyl-2,2′-diamine with 2,6-dichlorobenzaldehyde, 2,3-dichlorobenzaldehyde, 3,4-dichlorobenzaldehyde or salicylaldehyde in high yields, respectively. The catalytic asymmetric aziridination of alkenes has been examined using these novel chiral ligands. Excellent enantioselectivity in the aziridination of cinnamates has been achieved using the C₂-symmetric chiral ligand 1.     

Chiral diphenylselenophosphoramides: a new class of chiral ligands for the titanium(IV) alkoxide-promoted addition of diethylzinc to aldehydes

Chiral C₂-symmetric diphenylselenophosphoramides 1 and 2 were prepared from the reaction of diphenylselenophosphinic chloride with (1R,2R)-(−)-1,2-diaminocyclohexane and (1R,2R)-(+)-1,2-diphenylethylenediamine, respectively, in high yields. Another novel chiral ligand 3 was prepared from the reaction of diphenylselenophosphinic chloride with (R)-(+)-1,1′-binaphthyl-2,2′-diamine using butyllithium as the base. The ligands were used as catalytic chiral ligands in the titanium(IV) alkoxide-promoted enantioselective addition reaction of diethylzinc to aldehydes.     

Chiral diphenylthiophosphoramides: a new class of chiral ligands for the silver(I)-promoted enantioselective allylation of aldehydes

Chiral C₂-symmetric diphenylthiophosphoramides 1 and 2 were prepared in high yields from the reaction of diphenylthiophosphinic chloride with (1R,2R)-(−)-1,2-diaminocyclohexane and (1R,2R)-(+)-1,2-diphenylethylenediamine, respectively. Another novel chiral ligand 4 was prepared from reaction of diphenylthiophosphinic chloride with (R)-(+)-1,1′-binaphthyl-2,2′-diamine using butyllithium as a base. They were used as catalytic chiral ligands in the silver(I)-promoted enantioselective allylation reaction of aldehydes with allyltributyltin.     

Preparation and use of MeO-PEG-supported chiral diphosphine ligands: soluble polymer-supported catalysts for asymmetric hydrogenation

Two new chiral MeO-PEG-supported (R)-BINAP and (3R,4R)-Pyrphos ligands were synthesized and employed in the Ru(II)- and Rh(I)-catalyzed asymmetric hydrogenation of 2-(6′-methoxy-2′-naphthyl)propenoic acid 5 and prochiral enamides 10. The results showed that these new soluble polymeric catalysts exhibited high catalytic activity and enantioselectivity. Enantiomeric excesses (e.e.s) in the ranges 90–96% and 86–96% were achieved in the hydrogenation of 5 and 10, respectively. Furthermore, these catalysts could be recovered easily and the recycled catalysts were shown to maintain their efficiency in subsequent reactions.     

Development of axially chiral bis(arylthiourea)-based organocatalysts and their application in the enantioselective Henry reaction

Axially chiral bis(arylthiourea)-based organocatalyst 6b, prepared from (R)-(+)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl-2,2′-diamine, was found to be an effective chiral organocatalyst for the enantioselective Henry reaction of arylaldehydes with nitromethane to give the corresponding adducts in moderate enantioselectivities and good yields.     

Novel NMR chiral solvating agents derived from (1R,2R)-diaminocyclohexane: synthesis and enantiodiscrimination for chiral carboxylic acids

A series of new compounds, (1R,2R)-1-(1′,8′-naphthalimide)-2-aminocyclohexane 1 and its 4′-derivatives 2 and 3 derived from (1R,2R)-1,2-diaminocyclohexane have been synthesized conveniently and efficiently. ¹H NMR spectroscopy was employed to investigate their enantiodiscriminating ability. Compared with α-phenylethylamine, a commercially available chiral solvating agent (CSA), these compounds exhibited better enantiodiscriminating ability toward the chiral carboxylic acids we had chosen, distinguishing them as promising and practical CSAs.     

Chiral thiophosphoramide catalyzed asymmetric aryl transfer reactions for the synthesis of functional diarylmethanols

In this investigation, chiral thiophosphoramide 3d was easily prepared from chiral (1R,2R)-1,2-diphenylethylenediamine and then applied as an efficient chiral ligand in the catalytic asymmetric arylation reactions of various aromatic aldehydes. The corresponding diarylmethanol products were produced with good to excellent yields (up to 98%) and enantioselectivities (up to 94%). The recovery of chiral ligand 3d could be as high as 96%.     

New chiral phosphorus catalysts derived from (S)-binaphthol for highly enantioselective reduction of acetophenone by borane

New chiral (+)-2,2′-O,O-(1,1′-binaphthyl)-dioxo-N,N-diethylphospholidine 1 and its borane complex 3 were prepared from (S)-binaphthol and their use as catalysts in enantioselective borane reductions of prochiral acetophenone were investigated. Enantiomeric excesses of up to 98.5% have been obtained using 6 mol% of 1 at room temperature and using 6 mol% of 3 at 100°C.     

Synthesis and resolution of 2,2′-bis[di(p-tolyl)stibano]-1,1′-binaphthyl (BINASb); the first example of an optically active organoantimony ligand for asymmetric synthesis

Racemic 2,2′-bis[di(p-tolyl)stibano]-1,1′-binaphthyl (BINASb) (±)-2 has been prepared from 2,2′-dibromo-1,1′-binaphthyl 1 via 2,2′-dilithio-1,1′-binaphthyl intermediate, and has been resolved via the separation of a mixture of the diastereomeric Pd complexes 4A and 4B, derived from the reaction of (±)-2 with di-μ-chlorobis{(S)-2-[1-(dimethylamino)ethyl]phenyl-C,N}dipalladium(II) 3. The optically active BINASbs (S)-(+)-2 and (R)-(−)-2 have been shown to be effective chiral ligands for the rhodium-catalyzed asymmetric hydrosilylation of ketones.     

Supported catalysts incorporating BINOL units: towards heterogeneous asymmetric catalysis

Optically pure BINOL species were immobilized on two different types of support: organic (cross linked polystyrene) and inorganic (silica). The synthesis of the reticulated polystyrene gels was achieved via the radical crosslinking polymerization of a protected divinyl-(R)-BINOL derivative. The deprotection resulted in polystyrene networks incorporating free (R)-BINOL entities. Silica hybrid materials containing (R)-binaphthyl units were synthesized by sol–gel processing of a trialkoxysilylated (R)-BINOL-bis-carbamate precursor. Both materials were tested as chiral auxiliaries in enantioselective catalysis. The polystyrene-BINOL gels show similar catalytic properties compared to molecular (R)-BINOL and appears as a classical heterogenized catalyst system. Contrarily, the silica hybrid materials incorporating BINOL entities show significantly increased catalytic properties compared to the molecular catalyst in homogeneous solution. A supramolecular effect of the silica matrix on the stability and the selectivity of the catalyst system can be concluded. To cite this article: P. Hesemann, J.J.E. Moreau, C. R. Chimie 6 (2003).     

Synthesis of 3 or 3,3′-substituted BINOL ligands and their application in the asymmetric addition of diethylzinc to aromatic aldehydes

Three new substituted BINOL ligands (R)-3-[4,6-bis(dimethylamino)-1,3,5-triazin-2-yl]-1,1′-bi-2-naphthol (R)-1, (R)-3,3′-bis[4,6-bis(dimethylamino)-1,3,5-triazin-2-yl]-1,1′-bi-2-naphthol (R)-2 and 2,4-bis(2,2′-dihydroxy-1,1′-binaphthalen-3-yl)-6-(p-tolyl)-1,3,5-triazine (R,R)-3 have been obtained by directed ortho-lithiation or Suzuki cross-coupling process. Ligand (R)-1 shows improved catalytic properties for the asymmetric diethylzinc addition to aromatic aldehydes.     

Development of new chiral phosphine-salen type ligands and their application in the Cu(I)-catalyzed enantioselective Henry reaction

Chiral phosphine-salen type ligand L4 prepared from (R)-2-(diphenylphosphino)-1,1′-binaphthyl-2′-amine was found to be a fairly effective chiral ligand for Cu(I)-promoted enantioselective Henry reactions of arylaldehydes with nitromethane to give the corresponding adducts in moderate enantioselectivities and moderate to good yields.     

Pd(II)-catalyzed and diethylzinc-mediated asymmetric umpolung allylation of aldehydes in the presence of chiral phosphine-Schiff base type ligands

Chiral phosphine-Schiff base type ligand L3 prepared from (R)-(?)-2-(diphenylphosphino)-1,1′-binaphthyl-2′-amine was found to be a fairly effective chiral ligand for the Pd(II)-catalyzed and diethylzinc-mediated enantioselective umpolung allylation of aldehydes to give homoallylic alcohols in good yields, moderate enantioselectivities and high syn diastereoselectivities.     

Synthesis of chiral 3,3′-disubstituted 1,1′-binaphthyl-2,2′-disulfonic acids

A convenient synthesis of chiral 3,3′-disubstituted 1,1′-binaphthyl-2,2′-disulfonic acids (BINSA, 1) was developed. The key was directed ortho-lithiation of BINSA methyl ester 2 with n-BuLi and subsequent reaction with an electrophile. Electrophiles such as Br₂, I₂, Me₃SiOTf, and i-PrOB(Pin) reacted smoothly with 3,3′-dilithiated BINSA methyl ester, and the corresponding 3,3′-dihalo-, 3,3′-bis(trimethylsilyl)-, and 3,3′-diboryl-BINSA derivatives were obtained in yields of 21–78%. This simple synthetic method is highly attractive since the ability to prepare 3,3′-disubstituted BINOLs in advance can be useful.     

Catalytic asymmetric borane reduction of prochiral ketones by the use of diazaborolidine catalysts prepared from chiral β-diamines

The catalytic asymmetric borane reduction of prochiral ketones was examined in the presence of chiral diazaborolidine catalysts prepared in situ from chiral β-diamines and borane. Chiral secondary alcohols were obtained with modest to high enantiomeric excesses (up to 92% ee) using (S)-2-[(4-trifluoromethyl)anilinomethyl]indoline 2f.     

A modular design of ruthenium(II) catalysts with chiral C2-symmetric phosphinite ligands for effective asymmetric transfer hydrogenation of aromatic ketones

Hydrogen-transfer reduction processes are attracting increasing interest from synthetic chemists in view of their operational simplicity. The new chiral C₂-symmetric ligands N,N′-bis-[(1S)-1-sec-butyl-2-O-(diphenylphosphinite)ethyl]ethanediamide, 1 and N,N′-bis-[(1S)-1-phenyl-2-O-(diphenylphosphinite)ethyl]ethanediamide, 2 and the corresponding ruthenium complexes 3 and 4 have been prepared and their structures have been elucidated by a combination of multi-nuclear NMR spectroscopy, IR spectroscopy, and elemental analysis. ¹H–³¹P NMR, DEPT, ¹H–¹³C HETCOR, or ¹H–¹H COSY correlation experiments were used to confirm the spectral assignments. The catalytic activity of complexes 3 and 4 in transfer hydrogenation of acetophenone derivatives by iso-PrOH has also been studied. Under optimized conditions, these chiral ruthenium complexes serve as catalyst precursors for the asymmetric transfer hydrogenation of acetophenone derivatives in iso-PrOH and act as excellent catalysts, giving the corresponding chiral alcohols in 99% yield and up to 75% ee. This transfer hydrogenation is characterized by low reversibility under these conditions.     

New chiral phosphine-phosphonites derived from (2R,3R)-dimethyl tartrate, (S)-binaphthol and (1R,2S)-ephedrine

The reaction of 2-lithiophenyldiphenylphosphine with phosphorus trichloride afforded the new unsymmetric phosphine, dichloro(2-diphenylphosphinophenyl)phosphine (4). Condensation of 4 with (a) (2R,3R)-dimethyl tartrate or (b) (S)-binaphthol in the presence of triethylamine gave new chiral phosphine-phosphonite ligands, (2R,3R)-[2-(2′-(diphenylphosphino)phenyl)-4,5-bis(carbomethoxy)-1,3,2-dioxaphospholane] ((2R,3R)-5) and (S)-[2-(diphenylphosphino)benzene][1,1′-binaphthalen-2,2′-diyl]phosphonite] ((S)-6). The analogous reaction of 4 with (1R,2S)-ephedrine using N-methylmorpholine as the base, gave [2-(2′-(diphenylphosphino)phenyl)-3,4-dimethyl-5-phenyl-1,3,2-oxazaphospholidine] (7) as a 95:5 mixture of diastereoisomers.     

Chemical constituents from Piper marginatum Jacq. (Piperaceae)—antifungal activities and kinetic resolution of (RS)-marginatumol by Candida antarctica lipase (Novozym 435)

The leaves of Piper marginatum contain the antifungal compounds 3,4-methylenedioxypropiophenone 1, 2-methoxy-4,5-methylenedioxypropiophenone 2, 1-(3,4-methylenedioxyphenyl)propan-1-ol 3 (marginatumol), 5,4′-dihydroxy-7-methoxyflavanone 4 and 5,7-dihydroxy-4′-methoxyflavanone 5. The absolute configuration of natural marginatumol was determined as (+)-(R)-3 (ee 48%) by comparison of its optical properties with the chiral forms obtained by kinetic resolution of racemic 3 using Candida antarctica lipase (Novozym 435).     

Total synthesis of optically active liverwort sesquiterpenes,trifarienols A and B,using phenylethylamine as a chiral auxiliary

The imine of (rac)-2,3-dimethylcyclohexanone 10a with (S)-(−)-phenylethylamine was reacted with methyl acrylate to yield methyl (1′S,6′R)-3-(1′,6′-dimethyl-2′-oxocyclohexyl)propanoate 4a in 26% (97% ee) after hydrolysis. When (2RS,3R)-2,3-dimethylcyclohexanone 10b was used, the same product 4b was obtained in 59% yield (>99.5% ee) after hydrolysis. When (2RS,3R)-2,3-dimethylcyclohexanone 10b and (R)-(+)-phenylethylamine were used, the reaction underwent in only 5% yield, the products being 4c, 12, 13, 14, and 15. Thus, the reaction of 3b with methyl acrylate is a matched case, while that of 3c is a mismatched case. These phenomena are explained by the nonbonded interaction of methyl acrylate with chiral phenylethylamine and the methyl group at the 6′-position of the cyclohexanone ring in the transition state. The propanoate product 4b was successfully transformed into liverwort sesquiterpene (+)-trifarienol A 1 and (−)-trifarienol B 2 in 10 steps. We have developed an HPLC method to determine the ees of 2,2-disubstituted and 2,2,3-trisubstituted cyclohexanones using the corresponding pentafluorophenyl esters.     

Self-assembly of enantiopure and racemic 2,2′,6,6′-tetrasubstituted biaryl tectons into hydrogen bonded chiral squares and infinite chiral square layers

Both chiral and achiral hydrogen bonding o-,o-,o′-,o′-tetrasubstituted biaryls often exhibit unique self-assembling properties giving rise to chiral square cyclotetramers. The individual chiral squares self-assemble further with the formation of infinite layers which are either achiral or are chiral (homochiral). A priori analysis reveals various hydrogen bonding modes which may take part in the self-assembly, differing each from the other by structure and symmetry of the resulting squares and layers. Results of the theoretical analysis are compared with the experimental findings obtained from X-ray crystallographic analysis of three novel and two already known isosteric biaryl tectons, (S)-2a, (RS)-2a, 3a, (S)-5 and (RS)-5, respectively.