Synthesis of Dipeptides via Addition of N-(Nitroacetyl)amino-Acid Derivatives to Michael Acceptors: Scope,Stereoselectivity, and Absolute Configuration

Michael addition of N-nitroacetyl derivatives 1 of proline esters using KF under phase-transfer catalysis resulted in the formation of adducts 3–9 with chemical yields ranging from 40–90% (Scheme). Stereoselectivity of up to 51% was obtained on addition of benzyl N-(nitroacetyl)-L -prolinate ( 1a ). The absolute configuration at the newly created chiral centre was established in the case of 9 by carrying out a reductive acylation and comparing the product 10 with an authentic sample of ethyl N-(O⁵-ethyl N²-acetyl-L -glutam-1-yl)-L -prolinate (L, L - 10 ).     

cis–trans Enantiomerism in the Diels–Alder cycloadducts of 6-arylfulvenes with maleic anhydride: resolution of the exo adducts via the N-((1S)-1-(naphth-1-yl)ethyl)imide derivatives: assignment of the absolute configurations based on the crystal structure of an imide diastereomer

A new case of the uncommon cis–trans enantiomerism is presented. The titled anhydride adducts were prepared in good yields by the known reaction of three 6-arylfulvenes with maleic anhydride (aryl = phenyl, p-tolyl and p-anisyl). The exo adducts were converted to the corresponding imides by reaction with (1S)-1-(naphth-1-yl)ethylamine in ∼80% yields, and the resulting diastereomeric imides separated by silica gel column chromatography. They were hydrolysed and recyclised to the chiral anhydrides, in ‘one-pot’ with 10% NaOH–EtOH, followed by treatment with 2 M HCl, in ∼40% yields. The titled anhydrides were thus obtained in homochiral form, in enantiomeric purities (generally) of ∼90% as indicated by chiral HPLC. The chiral anhydrides were also converted to the corresponding imides (presumably stereospecifically), by treatment with ammonia solution in excellent yields. The crystal structure of one of the above diastereomeric imides (derived from 6-phenylfulvene) was determined, and based on the known (S)-configuration of the naphthylethylamine moiety, the ‘configurations’ of the original anhydride adducts were assigned.     

Asymmetric Morita–Baylis–Hillman reaction of chiral glyoxylates

The first Morita–Baylis–Hillman reaction of chiral glyoxylic acid derivatives, i.e. N-glyoxyloyl-(2R)-bornane-10,2-sultam and (−)-8-phenylmenthyl glyoxylate is described. The reaction with cyclic α,β-unsaturated ketones proceeded under the catalytic influence of dimethyl sulfide in the presence of titanium tetrachloride. The adducts were obtained with very high diastereoisomeric excess (over 95% d.e.) and typical yields of 78%. The absolute configuration of the newly created stereogenic center was established by X-ray crystallographic analysis.     

Chiral Diels–Alder reaction between cyclopentadiene and nitroso derivatives: thermal isomerisation/racemisation of the adducts

Cyclopentadiene nitroso adducts 1a and ent-1a were synthesised in good yields and good enantiomeric excess from chiral chloro-nitroso derivatives 4 and 5 in the d-mannose and d-ribose series, respectively. The thermal racemisation of these adducts occurred below room temperature. Some other chiral Diels–Alder nitroso adducts were prepared in the d-mandelic, l-prolinol and d-O-methylprolinol series and their thermal isomerisation was specified according to the N-substitution. A simple synthesis of the chiral amido-cyclopentenol (+)-2b, an important precursor for biological interesting compounds, is presented from ent-1a.     

Synthesis of cis-1,2-diol-type chiral ligands and their dioxaborinane derivatives: Application for the asymmetric transfer hydrogenation of various ketones and biological evaluation

Two cis-1,2-diol-type chiral ligands (T ₁ and T ₂ ) and their tri-coordinated chiral dioxaborinane (T _(1–2) B _(1–2) ) and four-coordinated chiral dioxaborinane adducts with 4-tert-butyl pyridine sustained by N → B dative bonds (T _(1–2) B _(1–2) -N) were synthesized and characterized by various spectroscopic techniques such as NMR (¹H, ¹³C, and ¹¹B), FT-IR and UV–Vis spectroscopy, LC–MS/MS, and elemental analysis. It was suggested that both ferrocene and trifluoromethyl groups played key roles in the catalytic and biological studies because they could tune the solubility of the chiral dioxaborinane complexes and adjust the strength of intermolecular interactions. To assess the biological activities of newly synthesized chiral dioxaborinane compounds, DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging, reducing power, antibacterial, DNA binding, and DNA cleavage activities were tested. Then, all chiral dioxaborinane complexes were investigated as catalysts for the asymmetric transfer hydrogenation of various ketones under suitable conditions. The results indicated that the chiral dioxaborinane catalysts performed well with high yields.     

Reductive Ring Opening of Ephedrine and Pseudo-Ephedrine-Derived Oxazolidinium Methiodides by Sodium Borohydride. A Direct Access to New Chiral Amine-Borane Adducts

Sodiun borohydride reacts with oxazolidinium methiodides derived from ephedrine and pseudoephedrine, in ethereal solvents, cleaving regioselectively the C-N bond of the ring and leading, in good yields, to chiral amine-borane adducts of know absolute configuration. The ¹HNMR data allow to predict the most stable conformation.     

Asymmetric Photochemical Synthesis of Chiral 5‐(R)‐(l)‐Menthyloxy‐4‐Cycloaminobutyrolactones

Through photocatalysed regiospecific and stereoselective additions of cycloamines to 5‐(R)‐(l)‐menthyloxy‐2 (5H)‐furanone (3), chiral 5‐(R)‐(l)‐menthyloxy‐4‐cycloaminobutyrolactones were synthesized. In the new asymmetric photoaddition of compound 3, the N‐methyl cyclic amines (4) gave novel chiral C? C photoadducts (5) in 24–50% isolated yields with d. e. ≥ 98%. However, the secondary cyclic amines (6) afforded optically active N? C photoadducts (7) in 34–58% isolated yields with d. e. ≥ 98% under the same condition. All the synthesized optically active compounds were identified on the basis of their analytical data and spectroscopic data, such as [α]₅₈₉²⁰, IR, ¹H NMR, ¹³C NMR, MS and elementary analysis. The photosynthesis of chiral butyrolactones and its mechanism were discussed in detail.     

Remote Sulfonamido Group Enhances Reactivity and Selectivity for Asymmetric Michael Addition of Nitroalkanes to α,β‐Unsaturated Aldehydes

The pyrrolidine–camphorsulfonamide‐based catalyst 1 a catalyzes the enantioselective conjugate addition of nitroalkanes to α,β‐unsaturated aldehydes in the presence of five equivalents of water in iPrOH to give the corresponding chiral Michael adducts in good yields and high enantioselectivities (up to 99 % ee) with a catalyst loading as low as 1 mol %.     

L-脯氨酸催化α-酮酰胺与甲基酮的不对称直接Aldol反应

用L-脯氨酸催化α-酮酰胺与甲基酮的不对称直接Aldol反应, 获得了不同光学活性的α-羟基酰胺, 产率在21%～99%之间, 对映选择性最高达到43% ee. 加成产物的结构用元素分析、红外光谱和核磁共振进行了表征.     

Cyclopentane-1,2-dione bis(tert-butyldimethylsilyl) enol ether in asymmetric organocatalytic Mukaiyama–Michael reactions

Cyclopentane-1,2-dione bis(tert-butyldimethylsilyl) enol ether readily undergoes organocatalytic reactions with α,β-unsaturated aldehydes resulting in Mukaiyama–Michael adducts which, after reduction of the aldehyde group and deprotection result in chiral 1,2-diketones (in mono-enolic form) in good yields (up to 66%) and with high stereoselectivity (up to 94% ee).     

1,4-Conjugate addition of 2-hydroxynaphthazarins to acyclic and cyclic α,β-unsaturated ketones. Prototropic ring-chain tautomerism of the adducts

TsOH-Catalyzed reactions of 6,7-disubstituted 2-hydroxynaphthazarins and acyclic or cyclic α,β-enones afforded the corresponding Michael-type adducts, viz., 3-substituted naphthazarins in 17–78% yields. ¹H and ¹³C NMR and IR spectroscopy showed that the adducts with cyclohexenone and methyl vinyl ketone exist in CDCl₃ solutions as mixtures of open-chain and cyclic tautomers, whereas the adducts with cyclopentenones exist only as the open-chain forms.     

Catalytic,asymmetric aza-Baylis–Hillman reaction of N-sulfonated imines with 2-cyclohexen-1-one and 2-cyclopenten-1-one in the presence of a chiral phosphine Lewis base

In the aza-Baylis–Hillman reaction of N-sulfonated imines with 2-cyclohexen-1-one or 2-cyclopenten-1-one, we found that by using (R)-2′-dimethylphosphanyl-[1,1′]binaphthalenyl-2-ol LB1 as a chiral phosphine Lewis base, the corresponding Baylis–Hillman adducts 2 or 3 can be obtained in good yields and moderate enantiomeric excess. The structure of this chiral phosphine Lewis base on chiral induction in this reaction has also been discussed.     

A ceric ammonium nitrate based oxidative cleavage pathway for the asymmetric aldol adducts of oxadiazinones derived from (1R,2S)-N-p-methoxybenzylnorephedrine

An N₄-p-methoxybenzyloxadiazinone has been prepared from (1R,2S)-norephedrine through a process of reductive amination, N-nitrosation, reduction, and cyclization. The oxadiazinone was acylated and employed in the asymmetric aldol addition reaction with aromatic and aliphatic aldehydes to yield aldol adducts in isolated yields ranging from 54% to 90%. Selected aldol adducts were treated with ceric ammonium nitrate in aqueous acetonitrile to afford the desired β-hydroxycarboxylic acids through a tandem process of oxidative cleavage of the N₄-p-methoxybenzyl group and acidic hydrolysis of the N₃-acyl side chain. The β-hydroxycarboxylic acids were recovered in high diastereomeric purity as determined by 500 MHz ¹H NMR spectroscopy and the absolute configuration was confirmed by polarimetry. The chiral auxiliary unit, the 3,4,5,6-tetrahydro-2H-1,3,4-oxadiazin-2-one (oxadiazinone), was converted into its corresponding 3,6-dihydro-2H-1,3,4-oxadiazin-2-one (oxadiazinone) through an oxidative pathway promoted by the ceric ammonium nitrate.     

Chiral tetraoxacalix[2]arene[2]triazine-based organocatalysts for Enantioselective Aldol reactions

Novel efficient chiral tetraoxacalix[2]arene[2]triazine-based organocatalysts have been designed and synthesized from the reaction of tetraoxacalix[2]arene[2]triazine with R/S-phenylethylamine or R/S-1-naphthylethylamine for the Aldol reaction of acetone with aromatic aldehydes to furnish the Aldol adducts in 71–92% yields with excellent enantioselectivities (78–99%).     

Chiral phosphine-catalyzed regio- and enantioselective allylic amination of Morita–Baylis–Hillman acetates

Enantioselective allylic substitution of Morita–Baylis–Hillman (MBH) acetates with phthalimide was realized in the presence of a novel l-proline-derived chiral trifunctional phosphine amide ligand to give the corresponding allylic amination adducts in good yields (70–95%) and in modest to good enantioselectivities (34–78% ee’s).     

Investigation of the active species in a Michael addition promoted by chirally modified tetrahydroborate

For the first time, asymmetric 1,4-addition of various malonates to enones has been carried out using tetrabutylammoniumtetrahydroborate (TBATB) in the presence of a chiral ligand. The Michael adducts were formed in reasonably good yields (61-67%) with moderate ee's at 0 °C. ¹¹B NMR spectroscopic studies explain this unexpected reactivity through the predominant formation of an aminodiol modified borate complex in the presence of a hydride acceptor.     

Catalytic asymmetric addition of arylboronic acids to N-Boc imines generated in situ using C2-symmetric cationic N-heterocyclic carbenes (NHCs) Pd diaquo complexes

The catalytic asymmetric addition of arylboronic acids to N-Boc imines generated in situ from stable and easily prepared α-carbamoyl sulfones was realized by using chiral cationic C₂-symmetric N-heterocyclic carbene (NHC) Pd²⁺ diaquo complexes 1a-c as the catalysts, producing the corresponding adducts in good to high yields (up to 89%) and good to high enantioselectivities (up to 90% ee).     

Chemistry of O-Benzoquinones and Masked O-Benzoquinones I. Diels-Alder Reactions of O-Benzoquinones with Dimethyl Acetylenedicarboxylate and Phenylacetylene

Diels-Alder reactions of six o-benzoquinones with dimethyl acetylenedicarboxylate has been examined. The yields of adducts vary with the natures of the o-benzoquinones, 3,4-Di-n-propyl-(1c), 3,6-di-n-propyl (1d). 3. 4-diallyl-(1e) and 3, 6-diallyl-o-benzoquinone (1f) are found to give bicyclic a-diketones exclusively without the formation of 1,4-dioxine derivatives, the yields ranging from 20 to 70%. In the case of 4, 5-dimethoxy-o-benzoquinone, dimethyl 4, 5-dimethoxyphthalate is produced in 42% yield, presumably derived from the decomposition of the corresponding initially formed α-diketone. 3, 6-Di-n-propyl-4, 5-dimethoxy-o-benzoquinone deteriorates without addition to dimethyl acetylenedicarboxylate upon heating. The additions of o-benzoquinones 1c , 1d and 1f to phenylacetylene are also studied. The yields of adducts, α-diketones, range from 23% to 82%.     

Metallosupramolecular Structures Derived from a Series of Diphosphine‐bridged Digold(I) Metalloligands with Terminal d‐Penicillamine

In this report, we describe our recent work on the development of a new family of chiral heteroleptic digold(I) metalloligands with mixed diphosphine and d ‐penicillaminate (d ‐pen), [Au₂(dppx)(d ‐pen‐S)₂]^2– (dppx = PPh₂(CH₂)_nPPh₂, n = 1–5) and their application for the construction of chiral multinuclear and metallosupramolecular structures. The reactions of the metalloligands with 3d metal ions produce a variety of chiral heterobimetallic structures retaining the digold(I) metalloligand structure, ranging from discrete trinuclear to infinite helix structures that depend on the type of dppx. In addition, monophosphine and triphosphine analogues of the metalloligands were designed, and their coordination behavior is discussed to show the essential properties and potential extensibility of this class of metalloligands.     

Catalytic, asymmetric aza-Baylis-Hillman reaction of N-sulfonated imines with activated olefins by quinidine-derived chiral amines

The chiral nitrogen Lewis base, tricyclic cinchona alkaloid derivative TQO, is an effective promoter in the catalytic, asymmetric aza‐Baylis–Hillman reaction of N‐sulfonated imines Ar? CH?NR′ 1 (R′ = Ts, Ms, Ns, SES) with various activated olefins such as methyl vinyl ketone (MVK), ethyl vinyl ketone (EVK), acrolein, methyl acrylate, phenyl acrylate, or α‐naphthyl acrylate to give the corresponding adducts in moderate to good yields with good to high ee (up to 99 %) at ?30 °C or 45 °C in various solvents, including DMF/MeCN (1:1, v/v). The first such reaction of 1 with the simplest Michael acceptor MVK and methyl acrylate has been achieved with excellent enantioselectivity. The adducts derived from MVK and EVK had the opposite absolute configuration to those from acrolein, methyl acrylate, phenyl acrylate, and α‐naphthyl acrylate. A plausible mechanism has been proposed on the basis of previous reports and the authors’ investigations. An effective bifunctional chiral nitrogen Lewis base–Brønsted acid system has been revealed in this type of aza‐Baylis–Hillman reaction.