Asymmetric Syntheses IV: Enantioselective Synthesis of (R)-Benzylic Amines Via Alkylation of D-Camphor Ketimine

An efficient asymmetric synthesis of (R)-benzylic amines in optical purity 36–90% had been achieved by alkylation of a chiral ketimine prepared from D-camphor and benzylamine. Diastereoselectivity in the alkylation is dependent on the alkyl halides.     

Stereomeric studies on the oxidation and alkylation of 4-thiazolidinones

Diastereoselectivity in the oxidation of different 4-thiazolidinones was discussed. Alkylation of these compounds with benzyl bromide was also studied. The stereoselectivity obtained was interpreted by the presence of the sulfoxide.     

Asymmetric Synthesis VIII: Enantioselective Synthesis of (R) or (S)-α-Substituted Benzylamines VIA Chiral Pinanone Ketimine Template

An excellent asymmetric synthesis of both (R) and (S)-α-substituted benzylamines in optical purity 90.4–99.9% has been achieved by alkylation of a chiral ketimine, prepared from pinanone and benzylamine. Diastereoselectivity in the alkylation is not dependent on the alkyl halides.     

Synthesis of (+)-goniothalesdiol and (+)-7-epi-goniothalesdiol

A total synthesis of (+)-goniothalesdiol, a 3,4-dihydroxy-2,5-disubstituted tetrahydrofuran isolated from Goniothalamus borneensis (Annonaceae), and its 7-epimer is reported using oxycarbonylation methodology for construction of polyhydroxylated substituted heterocycles. Diastereoselectivity of addition of organometallic reagents to 2,3-O-isopropylidene-d-threose derivatives using theoretical calculations based on the semiempirical PM5 was studied.     

Amplification of asymmetric induction in sequential reactions of bis-diazoacetates catalyzed by chiral dirhodium(II) carboxamidates

[reaction: see text] Two sequential intramolecular carbon-hydrogen insertion or cyclopropanation reactions of bis-diazoacetates using chiral dirhodium(II) carboxamidate catalysts are reported. The initial metal carbene transformation forms an excess of one enantiomer that with the second transformation further enhances stereocontrol (kinetic amplification). Diastereoselectivity and enantioselectivity for product formation are controlled by the catalyst.     

An expedient regio and diastereoselective synthesis of novel spiropyrrolidinylindenoquinoxalines via 1,3-dipolar cycloaddition reaction

We described an efficient and multicomponent approach for the synthesis of novel polyheterocyclic spiropyrrolidinylindenoquinoxalines via 1,3 dipolar [3+2] cycloaddition reaction of 3-methyl-4-nitro-5-alkenylisoxazoles, ninhydrin, orthophenylenediamine and benzyl amine. Excellent to good yields were obtained. Various isoxazole derivatives were used as dipolarophiles against substituted benzylamine and o-phenylenediamine. Diastereoselectivity was found to be variable and found to be dependent on the substitutions and their position on the aromatic ring of the reactants. This catalyst free and green approach is column free and does not even require a work up procedure.     

A new protocol for the acetoxyallylation of aldehydes mediated by indium in THF

A new precursor of a formal 1-hydroxy allyl anion is represented by 3-bromo-1-acetoxy-1-propene, which is synthesized by the ZnCl(2)-catalyzed addition of acetyl bromide to propenal. 3-Bromo-1-acetoxy-1-propene reacts with indium powder in THF to give the corresponding 3-acetoxylated ally indium complex, which regioselectively adds to aldehydes, affording monoprotected 1-en-3,4-diols. Diastereoselectivity mainly depends on the nature of the aldehyde; saturated aldehydes afford anti adducts, whereas the alpha,beta-unsaturated aldehydes preferentially lead to the syn isomers. Reaction: see text.     

Reactions of (E)-3,3,3-trichloro(trifluoro)-1-nitropropenes with enamines derived from cycloalkanones. A new type of ring-chain tautomerism in a series of cyclobutane derivatives and stereochemistry of the products

Depending on the reaction conditions, the reactions of (E)-3,3,3-trichloro-1-nitropropene with cyclohexanone enamines led to bicyclo[4.2.0]octanes or trisubstituted enamines, which are the ring-chain tautomers capable of reversible transformations. Diastereoselectivity of the reactions of (E)-3,3,3-trichloro(trifluoro)-1-nitropropenes with cycloalkanone enamines were studied, a series of hitherto unknown CX₃-containing nitroalkylated enamines and γ-nitro ketones were synthesized, the structures of novel compounds were determined by NMR spectroscopy and X-ray diffraction.     

Diastereoselectivity in the reduction of alpha-Oxy- and alpha-amino-substituted acyclic ketones by polymethylhydrosiloxane

Diastereoselectivity in the reduction of alpha-alkoxy-, alpha-acyloxy-, and alpha-alkylamino-substituted ketones with polymethylhydrosiloxane (PMHS) in the presence of fluoride ion catalysis was investigated. High syn-selectivity was observed in the reduction of alpha-alkoxy, alpha-acyloxy, and alpha-dialkylamino ketones. Reduction of alpha-monoalkylamino ketone proceeded in anti-selective manner with moderate selectivity. The observed selectivity is explained based on Felkin-Anh and Cram-chelate models.     

Lewis acid-mediated selective chlorinations of silyl enolate

A new method involving efficient, widely applicable, and highly selective alpha-chlorination of simple silyl enolate with Lewis acid and an alpha,alpha-dichloro-1,3-dicarbonyl controller unit was reported. Diastereoselectivity and enantioselectivity of the reaction were investigated. High reactivity and selectivity were achieved by using alpha,alpha-dichlorinated malonic ester.     

Novel synthons from mucochloric acid: the first use of alpha,beta-dichloro-gamma-butenolides and gamma-butyrolactams for direct vinylogous aldol addition

Novel 5-(1'-hydroxy)-gamma-butyrolactone and gamma-butyrolactam subunits were synthesized by direct vinylogous aldol addition of alpha,beta-dichloro gamma-butyrolactones and gamma-butyrolactams with aldehydes under basic conditions. Different bases and solvents were screened in the context of generating gamma-butyrolactones. Diastereoselectivity was observed and gamma-butenolides and gamma-butyrolactams showed opposite diastereoselectivity under the same reaction condition.     

Diastereoselective synthesis of novel 5-substituted morpholine-3-phosphonic acids: further exploitation of N-acyliminium intermediates

The first diastereoselective total synthesis of 5-substituted morpholine-3-phosphonic acids is reported. The principal feature of the synthesis is the introduction of a dimethyl phosphonate group into 5-substituted morpholin-3-ones. The procedure is based on the preparation of N-Boc-(S)-5-phenyl- and N-Boc-(S)-5-benzylmorpholin-3-one from l-phenylglycine and l-phenylalanine methyl esters, followed by the formation of the 3-methoxylated compounds and subsequent reaction with trimethyl phosphite in the presence of BF₃·OEt₂. Diastereoselectivity in the formation of cis-disubstituted products is in agreement with the nucleophilic addition to other methoxylated derivatives.     

Stereoselective synthesis of trifluoromethyl-substituted 1,2-diamines by aza-Michael reaction with trans-3,3,3-trifluoro-1-nitropropene

Aza-Michael addition of optically pure 4-phenyl-2-oxazolidinone to 3,3,3-trifluoro-1-nitropropene proceeds smoothly at low temperature with a high yield. Diastereoselectivity of the addition depends on the base used and lithiated species proved to be highly efficient affording 92% de. Optically pure 1,2-diamino-3,3,3-trifluoropropane is prepared in 58% yield from the aza-Michael addition product through a three-step procedure.     

Reaction of 2-alkyl pyridine N-oxide derivatives with Mosher’s acyl chloride: first example of stereoselective Boekelheide rearrangement

Treatment of 2-alkyl pyridine N-oxides with acylating reagents represents an established procedure for the introduction of oxygen functionality into alkyl group at the ortho position of N heteroaromatic rings. We have reported the first example of asymmetric Boekelheide rearrangement applied to a set of 2-alkyl-pyridine N-oxide derivatives using (R) Mosher’s acyl chloride as activator of the rearrangement to give, after hydrolysis, enantiomerically enriched 1-(2-pyridinyl)alkyl alcohol. Diastereoselectivity of the process was studied at low temperatures in different solvents, and was supported by a preliminary in silico modeling.     

Delineation of the factors governing reactivity and selectivity in epoxide formation from ammonium ylides and aldehydes

Diastereoselectivity in reactions of aryl-stabilised ammonium ylides are highly sensitive to the nature of the amine and the ylide substituent. DFT calculations are consistent with a mechanism in which reversibility in betaine formation [despite the high energy (and therefore instability) of ammonium ylides] is finely balanced due to the high barrier to ring closure.     

Stereochemistry of Phosphite Addition to Azomethine Bond of Achiral 2,6-Pyridinedicarbaldimines and Isophthalaldimines—A Comparative Study

Abstract

The addition of dialkyl H-phosphonates to isophthalaldimines 1a–d and pyridine-2,6-dicarboxaldimines 2a–d was investigated and led to the corresponding aminophosphonates. Diastereoselectivity of the addition to pyridine-2,6-dicarboxaldimines was lower than to isophthalaldimines. In contrast, addition of bis(trimethylsilyl) H-phosphonate to both groups of aldimines demonstrated that the diastereoselectivity in case of pyridine-2,6-dicarboxaldimines is comparable or even better than that for the isophthalic derivatives.     

Diastereoselective Manipulations of Bicyclo[m.1.0]alkane Derivatives. 2. Nucleophilic Additions to the Carbonyl Carbons of Bicyclo[m.1.0]alkan-2-ones(1)

Enantiomerically enriched bicyclo[m.1.0]alkan-2-ones having larger ring sizes between five and 16 members were prepared and subjected to additions of nucleophiles to the carbonyl carbon. Such additions were efficient and highly diastereoselective for all nucleophiles for bicycles with ring sizes greater than seven. Diastereoselectivity for these additions is rationalized by assuming early transition states and exposure of the same carbonyl face to the ring exterior in the vast majority of populated conformers for each bicyclic ketone.     

Gold-catalyzed heterocycle synthesis using homopropargylic ethers as latent electrophiles

[reaction: see text] Homopropargylic ethers with pendent nucleophiles, when subjected to Au catalysts in aqueous solvent, provide heterocyclic ketones. The reactions are efficient, tolerant of functionality and ambient atmosphere, and operationally simple. Diastereoselectivity can be predicted on the basis of product thermodynamics. This process demonstrates the viability of homopropargylic ethers to serve as latent electrophiles that can be unraveled under highly selective conditions to promote heterocycle formation through nucleophilic additions to alpha,beta-unsaturated ketones.     

The first asymmetric synthesis of alpha-sulfanylphosphonates

[reaction: see text] Diastereoselectivity of up to 88% was achieved for the synthesis of an alpha-mercapto gamma-unsaturated phosphonate using the readily available chiral dimenthylphosphonyl ester group and a carbanionic [2,3]-sigmatropic rearrangement. Absolute configuration of the newly formed chiral center of this nonracemic thiol was determined, and the corresponding phosphono thiolane and thiolane S-oxide were also stereoselectively prepared.     

Versatile synthesis of rare nucleotide furanoses

Direct activation of unprotected thioimidoyl furanosides yielded in only one step and few minutes a panel of rare uridine 5'-diphospho-furanoses. Diastereoselectivity of the reaction was tightly connected with reaction time, temperature, and nature of the furanosyl donor. This approach was totally selective since no ring expansion from the initial five-membered ring to the more stable pyranose form was observed.