Synthetic applications of ethyl 3-bromodifluoromethyl-3-benzyloxy-acrylate as a gem-difluorination building-block: Its reactions with aldehyde and epoxide

The effective kineticresolution of β-hydroxy esters prompted us to investigatethe asymmetric dehydration of β-styryl-β-hydroxy esters inmore detail. Herein we describe our recent progress tooptimize reaction conditions and to extend the scope of themethodology to various β-styryl substituents. Also, appli-cation of this methodology to the preparation of anenantioenriched neoflavonoid is presented.We have found that chiral ligand

Iron-Catalyzed Cross-Electrophile Coupling of Inert C–O Bonds with Alkyl Bromides

Catalytic asymmetric Reformatsky reactions of benzaldehyde with optically active menthyl bromoacetates in the presence of Zn-Cu couple were performed using 0.25 equiv. of (1R,2S) or (1S,2R)-dimethyl-2-amino-1,2-diphenyl ethanol as chiral ligand to obtain β - hydroxy esters with enantioselectivities up to 60.2%. The obvious double chiral induction effect was observed while chiral ligands matched with optically active substrates.

In recent years, our laboratories have been using camphor-based chiral ligands to catalyze asymmetric trimethylsilylcyanation of aldehydes and asymmetric reduction of prochiral ketones. In these two reactions, good isolated yields and ee values were achieved. In this study, this highly efficient and enantioselective chiral ligand was utilized to carry out the Mukaiyama-type aldol addition to aldehydes to afford β-hydroxy esters. The required amino alcohol was prepared from camphor in three steps, through the sequential formation of camphorquinone, camphorquinone oxime and amino alcohol. The amino alcohol was then reacted with salicylaldehyde to furnish the tridentate chiral ligand. The chiral ligand was reacted with Ti(OiPr)4 at 0 oC to afford the chiral catalyst which was used in the asymmetric aldol addition toward 14 different aldehydes under the same conditions. The best conditions were 20 mol% of the complex, the ratio of chiral ligand to Ti(OiPr)4 was 1.1:1, and hexane as the solvent in ice-bath. After 9 hours, the target product was obtained in 22-89% isolated yield and 5-64% of ee value, the ee value were determined by HPLC and rotation. Although the ee values are not very good, but for the synthesis of β- hydroxy esters, we provided a new method that is cheap and less of synthesis steps. We hope that we can use copper to replace titanium to catalyze the aldol addition enhance the enantiomeric excesses.

The synthesis of medium-chain-length β-hydroxy esters in good yield via the Reformatsky reaction is described. This work will be used as the basis for further investigation of hydroxyalkanoate polymers as potential feedstock for biofuel production.

Chiral Sulfide/Phosphoric Acid Cocatalyzed Enantioselective Intermolecular Oxysulfenylation of Alkenes with Phenol and Alcohol <i>O</i> -Nucleophiles

Design, Synthesis, and Applications of <i>ortho</i> -Sulfur Substituted Arylphosphanes

Enantiospecific synthesis of optically pure (3s)-hydroxy esters by the stereocontrolled yeast reduction of α-sulfenyl-β-ketoesters

SummaryTransition metal catalyzed [3 + 2] annulation of imines with double bonds via directed C-H activation offers a direct access to amino cyclic motifs. However, owing to weak coordination and steric hindrance, trifluoromethylated ketimines have been an unaddressed challenge for TM-catalyzed annulations. Here, a rhenium-catalyzed [3 + 2] annulation of trifluoromethylated ketimines with isocyanates via C(sp2)-H activation has been disclosed. This approach provides an efficient platform for rapid access to a privileged library of CF3-containing iminoisoindolinones and polyamides by utilizing challenging CF3-ketimines as the annulation component. The capability of gram scale synthesis, the post-functionalization of the cyclization adduct, the derivation of complex natural molecules and the facile synthesis of polyamides highlight a diversity of synthetic potential of the current methodology.

Spirocyclizative Remote Arylcarboxylation of Nonactivated Arenes with CO ₂ via Visible-Light-Induced Reductive Dearomatization

We describe a simple and convenient synthesis of the western zone of caprazamycin B using two catalytic asymmetric reactions as key elements of our approach. Desymmetrization of 3-methylglutaric anhydride with the (S)-Ni(2)-(Schiff base) complex as a catalyst furnished the chiral hemiester, and a thioamide-aldol reaction with mesitylcopper, (R,R)-Ph-BPE, and 2,2,5,7,8-pentamethylchromanol as a catalyst furnished the β-hydroxy thioamide in good yield and enantioselectivity. On further transformation, the thioamide functionality was converted to the corresponding β-hydroxy ester. Finally, a convergent synthesis of the western zone of caprazamycin B was achieved by connecting the hemiester, the β-hydroxy ester, and the 2,3,4-tri-O-methyl-l-rhamnose fragments.

The synthesis and reactivity of a wide range of titanium benzamidinates is described. Addition of 0.5 equiv of Me2Mg to the dichloride L2TiCl2 (L = PhC(NSiMe3)2) in Et2O yields the chloro−alkyl derivative L2Ti(Me)Cl in good yield. The addition of 2 equiv of PhCH2MgCl to the dichloride affords thermally sensitive L2Ti(CH2Ph)2 in moderate yield. Likewise, addition of 1 equiv of Me2Mg results in the clean formation of the dimethyl L2TiMe2. The dimethyl reacts with tert-butylamine in refluxing benzene to form the five-coordinate imido L2TiNCMe3, for which crystallographic data is presented. The imido reacts with acetone in C6D6 to form the bridging oxo derivative L2Ti(μ-O)2TiL[η1-NC(Ph)N(SiMe3)2]. Overnight reduction of the dichloride with 1% Na/Hg amalgam in tetrahydrofuran (THF) forms the Ti(III) derivative L2TiCl(THF), which is crystallized from hexanes in moderate yield. Carrying out the analogous reduction in toluene yields the base-free Ti(III) chloride, L2TiCl, for which crystallographic data is presented. Allowing the reaction (in toluene) to proceed for an additional 48 h results in further reduction and the formation of the end-on bound dinitrogen complex (L2Ti)2(μ-N2), which is isolated as dark blue crystals from hexanes in moderate yield. Reduction of L2Ti(Me)Cl with 1% Na/Hg amalgam in THF forms the Ti(III) methyl derivative which is isolated as the five-coordinate THF-free product L2TiMe upon evacuation and crystallization from hexamethyldisiloxane (HMDSO). The related Ti(III) alkyl L2TiCH2SiMe3 is readily prepared by reaction of LiCH2SiMe3 with L2TiCl in toluene. Carrying out the 1% Na/Hg amalgam reduction of the dichloride in the presence of CO results in the formation of the Ti(III) bridging-oxo species (L2Ti)2(μ-O), which is isolated in low yield. CO as the sole oxygen source is confirmed by the use of C18O, which yielded only labeled product. Analogous reduction in the presence of N,N,N‘,N‘-tetramethylethylenediamine (TMEDA) results in the C−N bond cleavage of an amidinate ligand and the cyclometalation of TMEDA. Two products, L2TiNSiMe3 and LTi[η2-Me3SiNC(H)Ph][η3-CH2N(Me)CH2CH2NMe2], are isolated in good yields by fractional crystallization from hexanes. The dinitrogen complex, (L2Ti)2(μ-N2), reacts with pyridine (Py) and 2,6-dimethylphenyl isocyanide (XylylNC) to form base adducts [L2Ti(Py)]2(μ-N2) and [L2Ti(CNXylyl)]2(μ-N2) without loss of the dinitrogen ligand. Crystallographic data for the Py adduct is presented. Oxidation reactions of (L2Ti)2(μ-N2) with a variety of oxygen and sulfur sources is reported. Reaction with dry O2 in the presence of pyridine gives the seven-coordinate peroxo complex L2Ti(η2-O2)Py. The related reaction with excess S8 yields the dark-green persulfido derivative L2Ti(η2-S2), for which crystallographic data is presented. The persulfido reacts overnight with Hg in toluene solution to give the bimetallic sulfido complex L2Ti(μ-S)2TiL[η1-NC(Ph)N(SiMe3)2], which is formed following a silyl-group migration. The analogous oxygen-containing product is best prepared by the reaction of powdered (L2Ti)(μ-N2) with dry O2. In the presence of excess pyridine, L2Ti(η2-S2) reacts with Hg to yield the terminal sulfido L2Ti(S)Py. The crystallographically characterized terminal-oxo derivative L2Ti(O)OPy is prepared by reaction of (L2Ti)(μ-N2) with an excess of pyridine N-oxide in toluene−pyridine.

Indanones are ubiquitous in biologically active compounds. Intramolecular hydroacylation of aldehydes and alkenes is an efficient and atom-economic route to indane rings. However, these reactions a...

Regioselective reaction of quinones with Reformatsky reagent: (BrZnCH 2CO 2Et·THF) 2

Inherently Chiral 6,7-Diphenyldibenzo[ <i>e,g</i> ][1,4]diazocine: Enantioselective Synthesis and Application as a Ligand Platform