Highly effective and selective FeBr3-promoted deuterium bromination/cyclization of 1,n-enynes.

A highly effective and selective FeBr3-promoted deuterium bromination/cyclization of 1,n-enynes is reported. On the one hand, the Lewis acid FeBr3 as a catalyst promotes cyclization of 1,n-enynes to afford deuterium heterocyclic frameworks with high efficiency. On the other hand, FeBr3 serves as the bromine source (with D2O as the deuterium source) to promote the formation of the desired deuterated pyrrole derivatives containing alkenyl bromide groups. This protocol provides an effective pathway to afford deuterated alkenyl brominative compounds as (Z)-isomers with high yields and selectivity, offering a new method for introducing 2H into organic compounds.

A Scalable and Metal-Free Synthesis of Indazoles from 2-Aminophenones and In Situ Generated De-Boc-Protected O-Mesitylsulfonyl Hydroxylamine Derivatives.

A one-pot metal-free protocol to access indazoles from easily available 2-aminophenones and hydroxylamine derivatives has been achieved. The reaction is operationally simple, mild, and insensitive to air and moisture. A broad range of indazoles were prepared in good to excellent yield (up to 97% yield), and the reaction displayed a broad functional group tolerance. The reaction was performed at gram scale, and its synthetic application was exhibited through the rapid and efficient preparation of bioactive molecule YC-3 and FDA-approved drug axitinib.

Cobalt-Catalyzed One-Pot Asymmetric Difunctionalization of Alkynes to Access Chiral gem-(Borylsilyl)alkanes.

Enantioselective cobalt-catalyzed one-pot hydrosilylation and hydroboration of terminal alkynes has been developed employing a cobalt catalyst generated from Co(acac)2 and (R,R)-Me-Ferrocelane. A variety of terminal alkynes undergo this asymmetric transformation, affording the corresponding gem-(borylsilyl)alkane products with high enantioselectivity (up to 98 % ee). This one-pot reaction combines (E)-selective hydrosilylation of alkynes and consecutive enantioselective hydroboration of (E)-vinylsilanes with one chiral cobalt catalyst. This protocol represents the most straightforward approach to access versatile chiral gem-(borylsilyl)alkanes from readily available alkynes with commercially available cobalt salt and chiral ligand.

Asymmetric Cobalt-Catalyzed Regioselective Hydrosilylation/Cyclization of 1,6-Enynes.

We report an enantioselective cobalt-catalyzed hydrosilylation/cyclization reaction of 1,6-enynes with secondary and tertiary hydrosilanes employing a catalyst generated in situ from the combination of Co(acac)2 and (R,Sp )-Josiphos. A wide range of oxygen-, nitrogen-, and carbon-tethered 1,6-enynes reacted with Ph2 SiH2 , (EtO)3 SiH, or (RO)2 MeSiH to afford the corresponding chiral organosilane products in high yields and up to >99 % ee. This cobalt-catalyzed hydrosilylation/cyclization also occurred with prochiral secondary hydrosilane PhMeSiH2 to yield chiral alkylsilanes containing both carbon- and silicon-stereogenic centers with excellent enantioselectivity, albeit with modest diastereoselectivity. The chiral organosilane products from this cobalt-catalyzed asymmetric hydrosilylation/cyclization could be converted to a variety of chiral five-membered heterocyclic compounds by stereospecific conversion of their C-Si and Si-H bonds without loss of enantiopurity.

Asymmetric Fluorination of α-Branched Aldehydes by Chiral Primary Amine Catalysis: Reagent-Controlled Enantioselectivity Switch.

Asymmetric fluorination of α-branched aldehydes catalyzed by chiral primary amines under mild conditions has been developed. Both enantiomers could be obtained with good yields (up to 96%) and a high enantioselectivity (up to 90% ee) by a simple swap of the fluorination reagents.

Catalytic Asymmetric Mannich Reaction with N-Carbamoyl Imine Surrogates of Formaldehyde and Glyoxylate.

N,O-acetals (NOAcs) were developed as bench stable surrogates for N-carbamoyl, (Boc, Cbz and Fmoc) formaldehyde and glyoxylate imines in asymmetric Mannich reactions. The NOAcs can be directly utilized in the chiral primary amine catalyzed Mannich reactions of both acyclic and cyclic ß-ketocarbonyls with high yields and excellent stereoselectivity. The current reaction offers a straightforward approach in the asymmetric synthesis of α- or ß-amino carbonyls bearing chiral quaternary centers in a practical and highly stereocontrolled manner.

Palladium-catalyzed enantioselective arylation of trichloro- or tri-/difluoroacetaldimine precursors.

A palladium-catalyzed asymmetric α-arylation of N-carbamoyl imine precursors containing CCl3, CF3 and CF2H is presented. This protocol provides facile access to a series of chiral α-aryl trichloroethylamines bearing various functional groups, with moderate to high yields (40-82% yield) and high enantioselectivity (80-99% ee).

Ligand-Enabled ortho-Selective C-H Olefination of Tertiary Aniline Derivatives.

A highly ortho-selective CAr-H olefination of tertiary anilines without a directing group was developed. This reaction tolerated various substituted arenes and olefin coupling partners, affording ortho-olefination products in moderate to good yields. Preliminary mechanistic studies showed that N-Ac-d-Ala, Ag2CO3, and BQ were the key factors for tuning the regioselectivity from para to ortho. Density functional theory was used to achieve a theoretical understanding of the ortho selectivity.

Gold-Catalyzed Cascade Reaction of 2-Alkynyl Aryl Azides with Enecarbamates for Direct Synthesis of α-(3-Indolyl)ketones.

α-(3-Indolyl)ketones are essential building blocks for the generation of biologically active molecules. We described a new method for the direct assembly of α-(3-indolyl)ketones through the cascade reaction of 2-alkynyl aryl azides with enecarbamates, in which the in situ generated α-imino gold carbene intermediate was trapped by enecarbamate to achieve umpolung reactivity of indole at the 3-position.

Asymmetric Double Oxidative [3 + 2] Cycloaddition for the Synthesis of CF3-Containing Spiro[pyrrolidin-3,2'-oxindole].

An asymmetric double oxidative [3 + 2] cycloaddition is reported. Oxidation of 3-((2,2,2-trifluoroethyl)amino)indolin-2-ones and ß-aryl-substituted aldehydes simultaneously and subsequent asymmetric cycloaddition in the presence of the chiral amino catalyst generated highly functionalized chiral CF3-containing spiro[pyrrolidin-3,2'-oxindole] with four contiguous stereocenters stereoselectively, which is characterized by directly constructing two C-C bonds from four C(sp3)-H bonds. This new method features mild conditions, broad substrate scope, and excellent functional group compatibility.

Regio- and Stereoselective Hydrochlorination/Cyclization of 1,n-Enynes by FeCl3 Catalysis.

A highly regio- and stereoselective hydrochlorination/cyclization of enynes has been reported by FeCl3 catalysis. A variety of enynes undergo this cyclization transformation with acetic chloride as the chlorine source and H2O providing protons via a cationic pathway. This protocol provides a cheap, simple, stereospecific, and effective cyclization to afford heterocyclic alkenyl chloride compounds as Z isomers with high yields (≤98%) and regioselectivity.

Catalytic Asymmetric Mannich Type Reaction with Tri-/Difluoro- or Trichloroacetaldimine Precursors.

A highly efficient catalytic asymmetric Mannich type reaction of CF3-, CF2H-, or CCl3-acetaldimine precursors by a chiral primary amine is presented. This protocol provides facile access to chiral CF3-, CF2H-, or trichloroethyl amines in excellent yields and high enantioselectivity (up to 99% yield, up to >99% ee).

Reagent-controlled enantioselectivity switch for the asymmetric fluorination of ß-ketocarbonyls by chiral primary amine catalysis.

A reagent-controlled enantioselectivity switch was uncovered in the asymmetric α-fluorination of ß-ketocarbonyls by a chiral primary amine catalyst. By a simple swap of fluorination reagents, both enantiomers of the quaternary fluorination adducts could be obtained with good yields and high enantioselectivity. Mechanistic studies disclosed dual H-bonding and electrostatic stereocontrolling modes for the catalysis.