A Sequential O‐Nitrosoaldol and Grignard Addition Process: An Enantio‐ and Diastereoselective Entry to Chiral 1,2‐Diols

Chiral 1,2‐diols have been prepared from α‐aminoxylated aldehydes or cyclohexanone and Grignard reagents with L ‐proline or its tetrazole derivative as the catalyst. The presence of the ate complex of CeCl₃?2 LiCl is essential for the high overall yields and good selectivities (see scheme; DMSO=dimethyl sulfoxide, THF=tetrahydrofuran, Tol=tolyl).

     

Synthesis of New C2‐Symmetric Chiral Bisamides from (1S,2S)‐Cyclohexane‐1,2‐dicarboxylic Acid

A series of new C₂‐symmetric (1S,2S)‐cyclohexane‐1,2‐dicarboxamides was synthesized from (1S,2S)‐cyclohexane‐1,2‐dicarbonyl dichloride and N‐benzyl‐substituted aromatic amines, which were prepared from 2‐aminopyridine, 2‐chloroaniline, and 2‐aminophenol via imine formation with benzaldehyde and subsequent reduction with NaBH₄. (1S,2S)‐N,N′‐Dibenzyl‐N,N′‐bis[2‐(benzyloxy)phenyl]cyclohexane‐1,2‐dicarboxamide was converted to (1S,2S)‐N,N′‐dibenzyl‐N,N′‐bis(2‐hydroxyphenyl)cyclohexane‐1,2‐dicarboxamide via hydrogenolysis in the presence of Pd(OH)₂ on active carbon powder.     

Novel and Stereospecific Synthesis of (2S)‐3‐(2,4,5‐Trifluorophenyl)propane‐1,2‐diol from D‐Mannitol

A stereospecific synthesis of (2S)‐3‐(2,4,5‐trifluorophenyl)propane‐1,2‐diol from D ‐mannitol has been developed. The reaction of 2,3‐O‐isopropylidene‐D ‐glyceraldehyde with 2,4,5‐trifluorophenylmagnesium bromide gave [(4R)‐2,2‐dimethyl‐1,3‐dioxolan‐4‐yl](2,4,5‐trifluorophenyl)methanol in 65% yield as a mixture of diastereoisomers (1 : 1). The Ph₃P catalyzed reaction of the latter with C₂Cl₆ followed by reduction with Pd/C‐catalyzed hydrogenation gave (2S)‐3‐(2,4,5‐trifluorophenyl)propane‐1,2‐diol with >99% ee and 65% yield.     

Enantioselective Construction of α‐Chiral Silanes by Nickel‐Catalyzed C(sp3)−C(sp3) Cross‐Coupling

An enantioselective C(sp³)?C(sp³) cross‐coupling of racemic α‐silylated alkyl iodides and alkylzinc reagents is reported. The reaction is catalyzed by NiCl₂/(S,S)‐Bn‐Pybox and yields α‐chiral silanes with high enantiocontrol. The catalyst system does not promote the cross‐coupling of the corresponding carbon analogue, corroborating the stabilizing effect of the silyl group on the alkyl radical intermediate (α‐silicon effect). Both coupling partners can be, but do not need to be, functionalized, and hence, even α‐chiral silanes with no functional group in direct proximity of the asymmetrically substituted carbon atom become accessible. This distinguishes the new method from established approaches for the synthesis of α‐chiral silanes.     

One‐Pot Synthesis of Novel Pyrrolo[1,2‐a]quinoxaline‐4(5H)‐ones Using Benzene‐1,2‐diamine,Acetylenedicarboxylates, and β‐Nitrostyrene Derivatives

The reaction between a variety of o‐phenylenediamines (=benzene‐1,2‐diamines), dialkyl acetylenedicarboxylates, and derivatives of nitrostyrene (=(E)‐(2‐nitroethenyl)benzene) in the presence of sulfamic acid (SA; H₃NSO₃) as catalyst led to the corresponding pyrrolo[1,2‐a]quinoxaline‐4(5H)‐one derivatives in high yields.     

1,2‐Bis(trifluoromethyl)ethene‐1,2‐dicarbonitrile: Enol Ethers and Ketene Acetals as Cycloaddition Partners

(E)‐ and (Z)‐1,2‐bis(trifluoromethyl)ethene‐1,2‐dicarbonitrile ((E)‐ and (Z)‐BTE, resp., =(E)‐ and (Z)‐2,3‐bis(trifluoromethyl)but‐2‐enedinitrile) were used as a stereochemical probe in studying (2+2) cycloadditions of acceptor with donor alkenes. The additions to methyl (E)‐ and (Z)‐propenyl ether gave rise to the eight conceivable cyclobutanes 8 , although in different ratios in reactions of (E)‐ and (Z)‐BTE. The ¹⁹F‐NMR data served the structural assignment and the quantitative analysis. The mechanistic discussion is based on rotations and ring closures of the assumed 1,4‐zwitterionic intermediates. Dimethylketene dimethyl acetal, methylketene dimethyl acetal, and ketene diethyl acetal show an increasing rate in their reactions with BTE as well as in the equilibration of the cycloadducts.     

1,2‐Bis(trifluoromethyl)ethene‐1,2‐dicarbonitrile and Vinyl Ethers: Cyclic Ketene Imines on the Pathway to 1 : 2 Cycloadducts

(E)‐ and (Z)‐1,2‐bis(trifluoromethyl)ethene‐1,2‐dicarbonitrile (BTE; (=E)‐ and (Z)‐1,2‐bis(trifluoromethyl)but‐2‐enedinitrile) were reacted with an excess of methyl vinyl ether, used as solvent, and furnished 1 : 2 adducts 6 (54%) and cyclobutanes 3 as 1 : 1 adducts (41%). The four diastereoisomeric bis‐adducts 6 (different ratios from (E)‐ and (Z)‐BTE) are derivatives of 1‐azabicyclo[4.2.0]oct‐5‐ene; X‐ray analyses and ¹⁹F‐NMR spectra revealed their structures. Since the cyclobutanes 3 are resistant to vinyl ether, the pathways leading to mono‐ and bis‐adducts must compete on the level of the intermediate l,4‐zwitterions 1 and 2 . The latter either cyclize to the cyclobutanes 3 or to six‐membered cyclic ketene imines 8 which accept a second molecule of vinyl ether to yield the bis‐adducts 6 . The occurrence of the highly strained ketene imines 8 gains credibility by comparison to stable seven‐membered cyclic ketene imines recently reported.     

Synthesis,characterization, and electrochemistry of monophosphine‐containing diiron propane‐1,2‐dithiolate complexes related to the active site of [FeFe]‐hydrogenases

Five monophosphine‐substituted diiron propane‐1,2‐dithiolate complexes as the active site models of [FeFe]‐hydrogenases have been synthesized and characterized. Reactions of complex [Fe₂(CO)₆{μ‐SCH₂CH(CH₃)S}] ( 1 ) with a monophosphine ligand tris(4‐methylphenyl)phosphine, diphenyl‐2‐pyridylphosphine, tris(4‐chlorophenyl)phosphine, triphenylphosphine, or tris(4‐fluorophenyl)phosphine in the presence of the oxidative agent Me₃NO·2H₂O gave the monophosphine‐substituted diiron complexes [Fe₂(CO)₅(L){μ‐SCH₂CH(CH₃)S}] [L = P(4‐C₆H₄CH₃)₃, 2 ; Ph₂P(2‐C₅H₄N), 3 ; P(4‐C₆H₄Cl)₃, 4 ; PPh₃, 5 ; P(4‐C₆H₄F)₃, 6 ] in 81%–94% yields. Complexes 2 – 6 have been characterized by elemental analysis, spectroscopy, and X‐ray crystallography. In addition, electrochemical studies revealed that these complexes can catalyze the reduction of protons to H₂ in the presence of HOAc.     

Phosphomolybdic Acid (PMA)–SiO2 as a Heterogeneous Solid Acid Catalyst for the One‐Pot Synthesis of 2H‐Indazolo[1,2‐b]phthalazine‐triones

Phosphomolybdic acid (PMA)–SiO₂ was found to be an efficient catalyst for the three‐component condensation reaction of phthalhydrazide, 1,3‐diketone, and aldehydes to produce 2H‐indazolo[1,2‐b]phthalazine‐triones in excellent yields. The catalyst can be recovered and reused without significant loss of activity.     

Synthesis of poly(D,L‐lactic acid‐alt‐glycolic acid) from D,L‐3‐methylglycolide

D ,L ‐3‐Methylglycolide (MG) was synthesized via two step reactions with a good yield (42%). It was successfully polymerized in bulk with stannous octoate as a catalyst at 110 °C. The effects of the polymerization time and catalyst concentration on the molecular weight and monomer conversion were studied. Poly(D ,L ‐lactic acid‐co‐glycolic acid) (D ,L ‐PLGA50; 50/50 mol/mol) copolymers were successfully synthesized from the homopolymerization of MG with high polymerization rates and high monomer conversions under moderate polymerization conditions. ¹H NMR spectroscopy indicated that the bulk ring‐opening polymerization of MG conformed to the coordination–insertion mechanism. ¹³C NMR spectra of D ,L ‐PLGA50 copolymers obtained under different experimental conditions revealed that the copolymers had alternating structures of lactyl and glycolyl. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4179–4184, 2000     

Facile and Efficient Synthesis of (R)‐4‐(Benzyloxy)‐3‐methylbutanenitrile: Toward Developing a Versatile Chiral Building Block

A practical synthesis of (R)‐4‐(benzyloxy)‐3‐methylbutanenitrile, a potential chiral building block, from the corresponding α‐keto ester in high yield and large scale was presented.     

A Simple Multistep Conversion of 1,2‐Dihydro‐1,1‐dimethoxynaphthalen‐2‐ones to (3,4‐Dihydro‐3,4‐dioxonaphthalen‐2‐yl)acetates

On irradiation (λ=350 nm) in the presence of 1,1‐dimethoxyethene, naphthalene‐1,2‐dionemonoacetals 1 regioselectively afford 1,1,4,4‐tetramethoxycyclobuta[a]naphthalen‐3‐ones 3 . Sequential deprotection of these bis‐acetals first lead to 1,1‐dimethoxycyclobuta[a]naphthalene‐3,4‐diones 4 and then to cyclobuta[a]naphthalene‐1,3,4‐triones 6 , which, in turn, are converted into (3,4‐dihydro‐3,4‐dioxonaphthalen‐2‐yl)acetates 7 by treatment with SiO₂/MeOH/air.     

Insertion Reactions of 1,2‐Disubstituted Olefins with an α‐Diimine Palladium(II) Complex

The migratory insertions of cis or trans olefins CH(X)?CH(Me) (X = Ph, Br, or Et) into the metal–acyl bond of the complex [Pd(Me)(CO)(ⁱPr₂dab)]⁺ [B{3,5‐(CF₃)₂C₆H₃}₄]^? ( 1 ) (ⁱPr₂dab = 1,4‐diisopropyl‐1,4‐diazabuta‐1,3‐diene = N,N′‐(ethane‐1,2‐diylidene)bis[1‐methylethanamine]) are described (Scheme 1). The resulting five‐membered palladacycles were characterized by NMR spectroscopy and X‐ray analysis. Experimental data reveal some important aspects concerning the regio‐ and stereochemistry of the insertion process. In particular, the presence of a Ph or Br substituent at the alkene leads to the formation of highly regiospecific products. Moreover, in all cases, the geometry of the substituents in the formed palladacycle was the same as in the starting olefin, as a consequence of a cis addition of the Pd–acyl fragment to the C?C bond. Reaction with CO and MeOH of the five‐membered complex derived from trans‐β‐methylstyrene (= [(1E)‐prop‐1‐enyl]benzene) insertion, yielded the 2,3‐substituted γ‐keto ester 9 with an (2RS,3SR)‐configuration (Scheme 3).     

Catalytic Asymmetric 1,2‐Addition of α‐Isothiocyanato Phosphonates: Synthesis of Chiral β‐Hydroxy‐ or β‐Amino‐Substituted α‐Amino Phosphonic Acid Derivatives

α‐Amino phosphonic acid derivatives are considered to be the most important structural analogues of α‐amino acids and have a very wide range of applications. However, approaches for the catalytic asymmetric synthesis of such useful compounds are very limited. In this work, simple, efficient, and versatile organocatalytic asymmetric 1,2‐addition reactions of α‐isothiocyanato phosphonate were developed. Through these processes, derivatives of β‐hydroxy‐α‐amino phosphonic acid and α,β‐diamino phosphonic acid, as well as highly functionalized phosphonate‐substituted spirooxindole, can be efficiently constructed (up to 99 % yield, d.r. >20:1, and >99 % ee). This novel method provides a new route for the enantioselective functionalization of α‐phosphonic acid derivatives.     

Synthesis of Functionalized Tetrahydro‐4‐oxoindeno[1,2‐b]pyrroles from Ninhydrin,Acetylenedicarboxylates, and Primary Amines

A one‐pot synthesis of dialkyl 1,3a,4,8b‐tetrahydro‐3a,8b‐dihydroxy‐1‐alkyl‐4‐oxoindeno[1,2‐b]pyrrole‐2,3‐dicarboxylates via three‐component reaction from indan‐1,2,3‐trione hydrate (ninhydrin), primary amines, and dialkyl acetylenedicarboxylates is described.