Predominant Retention Of Configuration Research Articles

Reduction of tertiary phosphine oxides to phosphine-boranes using Ti(Oi-Pr)4/BH3-THF

A new method for reduction of tertiary phosphine oxides leading to the formation of tertiary phosphine-boranes has been developed. The BH 3 -THF/Ti(O i -Pr) 4 reducing system enables conversion of triaryl, diarylalkyl and trialkylphosphine oxides directly to their borane analogues in good to high yields. In contrast to the previously reported protocols, the presence of activating groups in the structure of starting material is not necessary for the reaction to occur. The reaction is highly stereoselective and proceeds with predominant retention of configuration at the phosphorus atom. A plausible mechanism of reduction of the P O bond by BH 3 -THF/Ti(O i -Pr) 4 has been proposed.

The "Fully Catalytic System" in Mitsunobu Reaction Has Not Been Realized Yet.

An investigation of the recently reported "fully catalytic Mitsunobu reaction" using catalytic amounts of a phosphine reagent and an azo reagent has shown that although benzyl 4-nitrobenzoate is formed under the fully catalytic conditions, the same result is obtained if the hydrazine catalyst is omitted, indicating that this is not a Mitsunobu reaction. In addition, when the reaction between (-)-ethyl lactate and 4-nitrobenzoic acid was carried out using the "fully catalytic" method, the corresponding ester was formed but in very low yield and with predominant retention of configuration. Unfortunately, the system catalytic in phosphine reagent is incompatible with that in the azo reagent.

Acid catalyzed alcoholysis of sulfinamides: unusual stereochemistry, kinetics and a question of mechanism involving sulfurane intermediates and their pseudorotation.

The synthesis of optically active sulfinic acid esters has been accomplished by the acid catalyzed alcoholysis of optically active sulfinamides. Sulfinates are formed in this reaction with a full or predominant inversion of configuration at chiral sulfur or with predominant retention of configuration. The steric course of the reaction depends mainly on the size of the dialkylamido group in the sulfinamides and of the alcohols used as nucleophilic reagents. It has been found that bulky reaction components preferentially form sulfinates with retention of configuration. It has been demonstrated that the stereochemical outcome of the reaction can be changed from inversion to retention and vice versa by adding inorganic salts to the acidic reaction medium. The unusual stereochemistry of this typical bimolecular nucleophilic substitution reaction, as confirmed by kinetic measurements, has been rationalized in terms of the addition-elimination mechanism, A-E, involving sulfuranes as intermediates which undergo pseudorotations.

ChemInform Abstract: Imination of Sulfides and Sulfoxides with Sulfonylimino‐λ3‐bromane under Mild, Metal‐Free Conditions.

Exposure of sulfides and sulfoxides to trifluoromethanesulfonylimino(aryl)-lambda(3)-bromane in dichloromethane at 0 degrees C results in a facile transfer of the sulfonylimino group to sulfur atoms and affords N-triflylsulfilimines and -sulfoximines in high yields under transition-metal-free conditions. Imination of (R)-methyl p-tolyl sulfoxide proceeded with predominant retention of configuration at the stereogenic sulfur center. The Hammett plot afforded rho values of -0.58 for para-substituted thioanisoles and -0.49 for their equivalent sulfoxides, which suggests a buildup of positive charge on the sulfur atoms of sulfides and sulfoxides in the transition state. Calculations suggest a bimolecular nucleophilic-substitution mechanism on the negatively charged nitrogen atom of the sulfonylimino-lambda(3)-bromane, which involves the attack of a sulfide from the opposite side to bromine(III).

Imination of Sulfides and Sulfoxides with Sulfonylimino‐λ3‐Bromane under Mild, Metal‐Free Conditions

Exposure of sulfides and sulfoxides to trifluoromethanesulfonylimino(aryl)-lambda(3)-bromane in dichloromethane at 0 degrees C results in a facile transfer of the sulfonylimino group to sulfur atoms and affords N-triflylsulfilimines and -sulfoximines in high yields under transition-metal-free conditions. Imination of (R)-methyl p-tolyl sulfoxide proceeded with predominant retention of configuration at the stereogenic sulfur center. The Hammett plot afforded rho values of -0.58 for para-substituted thioanisoles and -0.49 for their equivalent sulfoxides, which suggests a buildup of positive charge on the sulfur atoms of sulfides and sulfoxides in the transition state. Calculations suggest a bimolecular nucleophilic-substitution mechanism on the negatively charged nitrogen atom of the sulfonylimino-lambda(3)-bromane, which involves the attack of a sulfide from the opposite side to bromine(III).

Regio- and Stereoselective Ring Opening of Enantiomerically Enriched 2-Aryl Oxetanes and 2-Aryl Azetidines with Aryl Borates

The regioselective ring opening of 2-aryl-substituted four-membered heterocyclic rings with phenols, including catechol, was achieved by the use of aryl borates in mild and neutral reaction conditions without the aid of any transition metal catalysts. While N-alkyl azetidines were found not to be reactive, optically active N-tosyl azetidines gave the corresponding beta-aryloxy amines in a racemic form, thus indicating the considerable carbocationic character of the transition state. The introduction of a hydroxyl group in the azetidine ring (i.e., an azetidinol), able to anchor the aryl borate and to direct the subsequent nucleophilic delivery, was shown to determine the ring-opening process with predominant inversion of configuration. When enantiomerically enriched 2-aryl oxetanes were used, the reduced extent of racemization observed (up to 93:7 er) was rationalized by an intramolecular delivery through a six-membered transition state, giving beta-aryloxy alcohols with a predominant retention of configuration (i.e., a syn-stereoselective ring opening). The aryloxy alcohols obtained, endowed with suitable functionalities, can be cyclized to give access to enantiomerically enriched 2-aryl-1,5-benzodioxepins.

Pyramidal Stability of Chiral-at-Metal Half-Sandwich 16-Electron Fragments [CpRu(P−P′)

The chiral-at-metal diastereomers (RRu,RC)- and (SRu,RC)-[CpRu(P−P′)Hal] (P−P′ = (R)-Prophos and (R,R)-Norphos, Hal = Cl, Br, and I) were synthesized, separated, and characterized by X-ray crystallography. Halide exchange and epimerization reactions were studied in 9:1 and 1:1 chloroform/methanol mixtures proceeding at room temperature or slightly above according to first-order. The rate-determining step in the Hal exchange reactions was the dissociation of the Ru−Hal bond, forming the pyramidal 16-electron intermediates (RRu,RC)- and (SRu,RC)-[CpRu(P−P′)]+, which maintain the metal configuration. These intermediates can invert their metal configuration or react with nucleophiles with retention of the metal configuration. The measured competition ratios showed that the inversion of the intermediates was slow compared to quenching with nucleophiles, indicating a high pyramidal stability of the 16-electron fragments (RRu,RC)- and (SRu,RC)-[CpRu(P−P′)]+ toward inversion in agreement with a basilica-type energy profile. Stereochemically this implies that substitution reactions in (RRu,RC)- and (SRu,RC)-[CpRu(P−P′)Hal] occur with predominant retention of configuration, however, accompanied by a well-defined share of inversion, a point overlooked when (RRu,RC)- and (SRu,RC)-[CpRu(Prophos)Cl] were extensively used as starting materials in the synthesis of a variety of organometallic derivatives. The rates of the approach to the epimerization equilibrium were much smaller than those of the Hal exchange reactions, because in the basilica-type energy profile the intermediates (RRu,RC)-/(SRu,RC)-[CpRu(P−P′)]+, formed in the cleavage of the Ru−Cl bond, have to cross another barrier of appreciable height for inversion. Increasing the methanol content of the solvent increased the rates of the Hal exchange and epimerization reactions. Obviously, the pyramidality of the fragments [CpRu(P−P′)]+ is enforced by the small P−Ru−P angles (83° in the Prophos derivatives and 86° in the Norphos derivatives of (RRu,RC)- and (SRu,RC)-[CpRu(P−P′)Hal]). Due to these small angles, intermediates (RRu,RC)- and (SRu,RC)-[CpRu(P−P′)]+ resist planarization and thus inversion of the metal configuration.

Substituent Effects on the Stereochemistry of Gas‐Phase Intracomplex Nucleophilic Substitutions

The mechanism and stereochemistry of the intracomplex solvolysis of proton-bound complexes [Y...H...M]+ between M = CH3 (18)OH and Y = 1-arylethanol [(S)-1-(para-tolyl)ethanol (1S), (S)-1-(para-chlorophenyl)ethanol (2S), (S)-1-(meta-alpha,alpha,alpha-trifluoromethylphenyl)ethanol (3S), (S)-1-(para-alpha,alpha,alpha-trifluoromethylphenyl)ethanol (4S), (R)-1-(pentafluorophenyl)ethanol (5R), (R)-alpha-(trifluoromethyl)benzyl alcohol (6R), and (R)-1-phenylethanol (7R)] have been investigated in the gas phase (CH3F; 720 Torr) in the 25-140 degrees C temperature range. Gas-phase solvolysis of [Y...H...M]+ (Y=2S, 3S, 4S, and 7R) leads to extensive racemization above a characteristic temperature t(#) (e.g. at t(#)>60 degrees C for 7R), whereas below that temperature the reaction displays a preferential retention of configuration. Predominant retention of configuration is instead observed in the intracomplex solvolysis of [Y...H...M]+ (Y=1S, 4S, 5R, and 6R) with the temperature range investigated (25 <or= T <or= 120 degrees C). These results indicate that the intracomplex solvolysis proceeds through the intermediacy of the relevant benzylic cations (Bz+), which is electrostatically coordinated to a H2O and a CH3 (18)OH molecule (a pure SN1 mechanism). The obtained gas-phase mechanism is discussed in the light of related solution data. It is concluded that the stereochemistry of unimolecular solvolytic reactions is determined by the lifetime and the dynamics of the species involved and, if occurring in solution, by the nature and the dynamics of the solvent cage as well.

On the stereochemistry of anion-accelerated [1,3]-sigmatropic rearrangement of 2-vinylcyclobutanols

Stereochemical studies on the oxyanion-accelerated [1,3]-sigmatropic rearrangement reactions of nonracemic cis- and trans-2-(1-cyclohexenyl)cyclobutanols are described. Epimerization of cis-2-(1-cyclohexenyl)cyclobutanol to the trans-isomer at −20°C was found to proceed with predominant retention of configuration, the degree of which was enhanced by an increasing amount of 18-crown-6.

Troposelective Substitutions in Microsolvated Systems

The mechanism and the stereochemistry of the intracomplex "solvolysis" of the proton-bound complexes I(X)() between CH(3)(18)OH and (R)-(+)-1-aryl-ethanol (1(R)()(X)(); aryl = phenyl (X = H); pentafluorophenyl (X = F)) have been investigated in the gas phase in the 25-100 degrees C temperature range. The results point to intracomplex "solvolysis" as proceeding through the intermediacy of the relevant benzyl cation III(X)() (a pure S(N)1 mechanism). "Solvolysis" of I(H)() leads to complete racemization at T > 50 degrees C, whereas at T < 50 degrees C the reaction displays a preferential retention of configuration. Predominant retention of configuration is also observed in the intracomplex "solvolysis" of I(F)(). This picture is rationalized in terms of different intracomplex interactions between the benzylic ion III(X)() and the nucleophile/leaving group pair, which govern the timing of their reorientation within the electrostatic complex. The obtained gas-phase picture is discussed in the light of related gas-phase and solution data. It is concluded that the solvolytic reactions are mostly governed by the lifetime and the dynamics of the species involved and, if occurring in solution, by the nature of the solvent cage. Their rigid subdivision into the S(N)1 and S(N)2 mechanistic categories appears inadequate, and the use of their stereochemistry as a mechanistic probe can be highly misleading.

ChemInform Abstract: 1-(3,4-Dihydro-4-oxoquinazolin-3-yl)aziridines (Q-Substituted Aziridines): Ring-Opening Reactions with C-N Bond Cleavage and Preparation of Q-Free Chirons.

The presence of the Q group in ring-opening reactions of N-(Q)-aziridines 3, 4, 5 and 6 has been found to be advantageous in the following ways, (i) nucleophilic ring-opening by cuprate or by azide with inversion of configuration is assisted by the electron-withdrawing character of the Q group, (ii) ring-opening of aziridines 5 or 6 to the corresponding alcohols 36 and 23 with retention of configuration can be accomplished by participation of the Q group: the Q carbonyl oxygen becomes the hydroxy oxygen in the alcohol product, (iii) the combined effects of the electron-withdrawing Q group and ring strain allow preparation of individual aziridine N-invertomers 3 and 4 whose ring-opening with hydrogen chloride in dichloromethane proceeds with complementary stereochemistry. The Q group is also believed to be involved in ring-opening of aziridines 5 and 6 mediated by samarium(III) nitrate hexahydrate with predominant retention of configuration. Reductive removal of the Q group from these ring-opened products gave chirons 12, 19 and 21.

Ruthenacycles with stereogenic metal centers:: Synthesis and characterization of cycloruthenated ( R) C-(+)- N, N-dimethyl-α-(2-naphthyl) ethylamine (TMNA); crystal structures of [(η 6-C 6H 5Me)Ru(TMNA)(X)], (X=Cl, Br, I)

The transmetallation reaction of enantiomerically pure ( R C)-{ HgCl[C 10H 6CH(Me)N Me 2]} with the [(η 6-arene)RuCl 2] 2 dimer, where η 6-arene=C 6H 5-Me (toluene), in CH 3CN at ambient temperature forms a mixture of two diastereomeric ruthenacycles [( S Ru, R C) – a, major, and ( R Ru, R C) – a′, minor] of the type {(η 6-arene) Ru[C 10H 6CH(Me)N Me 2](Cl)} ( 1a, a′) in good chemical and optical yields. The diastereoselectivity of chloride substitution in 1a, a′ by bromide and iodide has been determined by 1H and 13C{ 1H} NMR spectroscopy and single-crystal X-ray crystallography. The diastereoselectivity of this type of transmetallation reaction varies as a function of both the electronic nature of the (η 6-arene) ligand attached to the ruthenium center and the steric nature of the chiral arylamine (de is the diastereomeric excess): [(η 6-benzene)Ru(TMNA)Cl] (TMNA=[C 10H 6CH(Me)NMe 2]), 8a, a′, (92% de)>[(η 6-benzene)Ru(TMBA)Cl], (TMBA=[C 6H 4CH(Me)NMe 2]), 5a, a′, (90.4% de)>[(η 6-toluene)Ru(TMNA)Cl], 1a, a′, (87.5% de)>[(η 6-toluene)Ru(TMBA)Cl], 4a, a′, (86.7% de). The diastereoselectivity of the substitution reactions generally increases with increasing steric bulk of the incoming ligand and proceeds with predominant retention of configuration at ruthenium.

Chloride Substitution Reactions of Cycloruthenated (R)(C)-(+)-N,N-Dimethyl(1-phenylethyl)amine with Pseudohalides: Ruthenium Atom Stereochemistry.

The diastereoselectivity of chloride substitution by the pseudohalides azide, nitrite, thiocyanate, and cyanate in has been determined by a combination of (1)H and (13)C{(1)H} NMR spectroscopy, UV-visible spectroscopy, circular dichroism, infrared spectroscopy, and single-crystal X-ray crystallography. These chloride substitution reactions proceed with predominant retention of configuration at ruthenium. For the ambidentate ligands thiocyanate and nitrite, the major bonding mode is through their nitrogen donor atoms.

Synthesis, Characterization, and Diastereoselectivity of Chloride Substitution Reactions of Cycloruthenated (R)C-(+)-N,N-Dimethyl-α-(2-naphthyl) Ethylamine

The transmetalation reaction of enantiomerically pure 1, with [(η6-C6H6)RuCl2]2 in CH3CN at ambient temperature forms a mixture of two diastereomeric ruthenacycles (SRu, RC), 2a, (96%) and (RRu, RC), 2a‘, (4%) of the type in good chemical and optical yields. The diastereoselectivity of chloride substitution in 2a,a‘ by bromide, iodide, azide, cyanate, thiocyanate, nitrite, allylisonitrile, and selected nitrogen and phosphorus donor ligands has been determined by an appropriate combination of 1H, 13C{1H}, and 31P{1H} NMR spectroscopy, UV−visible spectroscopy, circular dichroism, and single-crystal X-ray crystallography. The diastereoselectivity generally increases with increasing steric bulk of the incoming ligand and proceeds with predominant retention of configuration at ruthenium. The ambidentate ligands, cyanate, thiocyanate, and nitrite all bond to ruthenium exclusively through their nitrogen donor atoms.

Photo-Arbuzov Rearrangements of Benzylic Phosphites. Stereochemistry at Migratory Carbon

The stereochemistry of the photo-Arbuzov rearrangement of the benzylic phosphite trans-(R,R‘)-10 to the corresponding phosphonate, 11, has been determined by 31P NMR spectroscopy and X-ray crystallography. The reaction is shown to occur with predominant retention of configuration at the stereogenic migratory carbon center of configuration R‘ in starting trans-(R,R‘)-10 and the predominant product cis-(R,R‘)-11. Thus, reaction of optically active phosphoramidite 13 (R/S ratio 98/2, 96% ee) with 1-phenylethanol of high optical purity (R‘/S‘ ratio, 97/3, 94% ee) gives phosphite trans-10 (cis/trans ratio ≥ 97/3) almost entirely as the single enantiomer, trans-(R,R‘)-10. Irradiation of trans-(R,R‘)-10 in acetonitrile with 254 nm ultraviolet light converted it cleanly to two diastereomers of phosphonate cis-11 in 80/20 ratio (31P NMR). The major (80%) isomer was isolated, recrystallized, and shown by X-ray crystallography to be cis-(R,R‘)-11. The lesser (20%) product is identified, on the basis of its 31P NMR c...

Diastereoselectivity of Chloride Substitution Reactions of Cycloruthenated (R)C-(+)- and (S)C-(−)-Dimethyl(1-phenylethyl)amine

The diastereoselectivity of chloride substitution in the two enantiomeric ruthenacycles (SRu, RC)- and (RRu, SC)-{(η6-C6H6)Ru(C6H4CH(Me)N(Me)2]}} by bromide, iodide, and selected nitrogen and phosphorus donor ligands has been determined by a combination of 1H, 13C{1H}, and 31P{1H} NMR spectroscopy, UV−visible spectroscopy, circular dichroism, and, where possible, single-crystal X-ray crystallography. The diastereoselectivity generally increases with increasing steric bulk of the incoming ligand and proceeds with predominant retention of configuration at ruthenium.

Reactions of coordinated phosphines and arsines: stereoselective reactions at the chlorophosphine- P stereocentre in the complex [( R★), ( R★, R★)]-(±)-[(η 5-C 5H 5){1,2-C 6H 4(PMePh) 2}-Fe(PClMePh)]PF 6·CH 2Cl 2

The reaction of ( R ★, R ★)-(±)-[(η 5-C 5H 5){1,2-C 6H 4(PMePh)2}Fe(NCMe)]PF 6 with (±)-chloromethylphenylphosphine in boiling dichloromethane affords a separable mixture of two diastereomeric iron complexes, epimeric at the chlorophosphine- P stereocentre, viz. [( R ★), ( R ★, R(su★)]-(±)- and [( S ★), ( R ★, R ★)±)-[(η 5-C 5H 5){1,2-C 6H 4(PMePh) 2}Fe(PClMePh)]PF 6, with the diastereomeric ratio ( R ★), ( R ★, R ★)/( S ★), ( R ★, R(su★) = 3/1. The crystal structure of the ( R ★), ( R ★, R ★) diastereomer (with one molecule of solvation of dichloromethane) has been determined. By use of the optically active acetonitrile complex, optically pure [R-[( S ★), ( R ★, R ★)]]-(+) 589-(η 5-C 5H 5){1,2-C 6H 4(PMePh) 2}Fe(PClMePh)]PF 6·Me 2CO was obtained, the first complex to be isolated containing resolved (±)-PClMePh. Alkylations of the diastereomeric chlorophosphine-iron complexes with Grignard reagents in tetrahydrofuran at 20°C are highly stereoselective, with predominant retention of configuration at phosphorus. The reaction of ethylmagnesium bromide with the ( R ★), ( R ★, R ★) diastereomer of the (±)-chloromethylphenylphosphine-iron complexes gives the (±)-ethylmethylphenylphosphine-iron complex with ( R ★), ( R ★, R ★)I(S*), ( R ★, R ★) = 1/3; benzylmagnesium bromide gives the (±)-benzylmethylphenylphosphine iron complex with ( R ★), ( R ★, R ★)/( S ★), ( R ★, R ★) = 1/8. Sodium borohydride reductions of the (±)-chloromethylphenylphosphine- iron complexes are also stereoselective, with predominant retention of configuration at phosphorus in each case. Thallium(I) phenoxide, however, when allowed to react with the ( R ★), ( R ★, R ★) diastereomer of the (±)-chloromethylphenyl-phosphine- iron complex in boiling tetrahydrofuran, gives the corresponding (±)-methylpheno-xyphenylphosphine-iron complex, with predominant inversion of configuration at phosphorus (( R ★), ( R ★, R ★)I(S*), ( R ★, R ★) = 1/6).

Nucleic acid related compounds. 76. Synthesis of 5'(E and Z)-chloro-4',5'-didehydro-5'-deoxyadenosines via chlorination and thermolysis of adenosine 5'-sulfoxides. Mechanism-based inhibition of S-adenosyl-L-homocysteine hydrolase

Treatment of 2',3'-di-O-acetyl-5'-S-(4-methoxyphenyl)-5'-thioadenosine (1a), or its sulfoxides 2a (S r ) and 3a(S s ), with iodobenzene dichloride and potassium carbonate in acetonitrile resulted in formation of the 5'-chloro(and 5',5'-dichloro)-5'-deoxy-5'-[(4-methoxyphenyl)sulfinyl]adenosines 4a, 5a, 6a, and minor diastereomers. Deprotection of 5a gave 5'(S)-chloro-5'-deoxy-5'-[(4-methoxyphenyl)-sulfinyl]adenosine [5b(5'S,S s ] whose stereochemistry and conformation were established by X-ray crystallography. The α-chlorination of sulfoxydes 2a(S r ) and 3a(S s ) occured with predominant retention of configuration at sulffur. Thermolysis of the α-chloro sulfoxides and deprotection gave the chloromethylene derivatives

ChemInform Abstract: The Reduction by Deuterium on Platinum Black of exo‐2‐Norbornyl* and endo‐2‐Norbornyl* to Norbornane‐2‐d1 Occurs with Predominant Retention of Configuration.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The reduction by deuterium on platinum black of exo-2-norbornyl* and endo-2-norbornyl* to norbornane-2-d1 occurs with predominant retention of configuration

The heterogeneous, platinum-catalyzed hydrogenation of (diolefin) dialkylplatinum(II) complexes (DO)PtR 2 ) on platinum black produces alkanes by reduction of the diolefin and alkylplatinum moieties; the platinum(II) is reduced to platinum(0) and becomes part of the catalyst. This paper reports and investigation of the stereochemistry of the reduction of C* bonds in heterogeneous hydrogenations, based on the adsorption of (DO)PtR 2 on platinum black to generate R* groups