Nickel-Catalyzed Electrophilic Amination of the Biphenylene C-C σ-Bond.

A nickel-catalyzed three-component carboamination of the biphenylene C-C σ-bond has been developed. Arylboronates and hydroxylamine derivatives work as carbon nucleophiles and nitrogen electrophiles, respectively, and the corresponding difunctionalized ring-opening products are obtained in good yields. The arylboronate nucleophile can be replaced with B2pin2 (boron nucleophile) and H-Si(OMe)3 (hydride nucleophile), thus allowing for the aminoboration and hydroamination of the biphenylene C-C σ-bond under similar nickel catalysis.

Nickel-catalyzed Nucleophilic C-Borylation of Imines.

Application of bioisostere plays an important role in drug discovery. α-Aminoboronic acid is the familiar bioisostere of α-amino acid. Developing reactions for the synthesis of a wide variety of α-aminoboronic acid is one important task for synthetic chemistry. Herein, we report the development of nucleophilic C-borylation chemistry for N-arylimines catalyzed by nickel. The reaction proceeds through the insertion of a borylnickel species into the C=N bond to afford the corresponding α-aminoboronate, which was isolated as acetamide after trapping with acetic anhydride. N-Benzyl imine is also tolerated by the developed reaction.

Synthesis of α-Aminophosphonates by Umpolung-Enabled Cu-Catalyzed Regioselective Hydroamination.

A copper-catalyzed regioselective hydroamination of α,ß-unsaturated phosphonates has been developed to form corresponding α-aminophosphonates of interest in medicinal chemistry. The introduction of an umpolung, electrophilic amination strategy with the hydroxylamine derivative is the key to achieving the α-amination regioselectivity, which is otherwise difficult under the conventional nucleophilic hydroamination conditions with the parent amine. Asymmetric synthesis with a chiral bisphosphine ligand and application to a related silylamination reaction are also described.

anti-Selective synthesis of ß-boryl-α-amino acid derivatives by Cu-catalysed borylamination of α,ß-unsaturated esters.

A copper-catalysed regio- and diastereoselective borylamination of α,ß-unsaturated esters with B2pin2 and hydroxylamines has been developed to deliver acyclic ß-boryl-α-amino acid derivatives with high anti-diastereoselectivity (up to >99 : 1), which is difficult to obtain by the established methods. A chiral phosphoramidite ligand also successfully induces the enantioselectivity, giving the optically active ß-borylated α-amino acids. The products can be stereospecifically transformed into ß-functionalised α-amino acids, which are of potent interest in medicinal chemistry.

Synthesis of ß-Silyl-α-amino Acid Derivatives by Cu-Catalyzed Regio- and Enantioselective Silylamination of α,ß-Unsaturated Esters.

A copper-catalyzed silylamination of α,ß-unsaturated esters with silylboranes and hydroxylamines has been developed to afford the corresponding ß-silyl-α-amino acid derivatives, which are of great interest in medicinal and pharmaceutical chemistry. Additionally, by using a suitable chiral bisphosphine ligand, the asymmetric induction is possible, delivering the optically active ß-silyl-α-amino acids with synthetically acceptable diastereomeric ratios (55:45-82:18 dr) and high enantiomeric ratios (81:19-99:1 er).

An umpolung-enabled copper-catalysed regioselective hydroamination approach to α-amino acids.

A copper-catalysed regio- and stereoselective hydroamination of acrylates with hydrosilanes and hydroxylamines has been developed to afford the corresponding α-amino acids in good yields. The key to regioselectivity control is the use of hydroxylamine as an umpolung, electrophilic amination reagent. Additionally, a judicious choice of conditions involving the CsOPiv base and DTBM-dppbz ligand of remote steric hindrance enables the otherwise challenging C-N bond formation at the α position to the carbonyl. The point chirality at the ß-position is successfully controlled by the Xyl-BINAP or DTBM-SEGPHOS chiral ligand with similarly remote steric bulkiness. The combination with the chiral auxiliary, (-)-8-phenylmenthol, also induces stereoselectivity at the α-position to form the optically active unnatural α-amino acids with two adjacent stereocentres.

Cu-Catalyzed Reductive gem-Difunctionalization of Terminal Alkynes via Hydrosilylation/Hydroamination Cascade: Concise Synthesis of α-Aminosilanes.

A copper-catalyzed reductive gem-difunctionalization of terminal alkynes with hydrosilanes and hydroxylamines has been developed. The reaction proceeds via hydrosilylation/hydroamination cascade, and the readily available and simple terminal alkynes can be transformed into the corresponding α-aminosilanes of medicinal interest in a single operation. Additionally, the use of chiral bisphosphine ligand successfully makes the reaction enantioselective to deliver the optically active α-aminosilanes with good enantiomeric ratios.

Ni-Catalyzed α-Selective C-H Borylations of Naphthalene-Based Aromatic Compounds.

The ability of α-borylated naphthalene-based aromatic compounds is important because it provides ready access to interesting novel extended π-systems. In this report, we disclose the Ni-catalyzed α-selective C-H borylations of naphthalene-based aromatic compounds. The reaction proceeds with peri-xanthenoxanthene and other aromatic compounds to regioselectively afford the α-borylated products without directing groups. The selectivities of these transformations are different from those of Ir-catalyzed C-H borylation reactions and can be used in a complementary manner.

Copper-Catalyzed Electrophilic Amination of gem-Diborylalkanes with Hydroxylamines Providing α-Aminoboronic Acid Derivatives.

A copper-catalyzed electrophilic amination of gem-diborylalkanes with hydroxylamines has been developed. The key to its success is the use of the Me3Si-modified 1,2-bis(diphenylphosphino)benzene ligand. Additionally, the reactivity of neopentylglycol derivatives compared to that of commonly used pinacol-derived ones is found to be higher, particularly in the case of relatively sterically congested substrates. The copper catalysis presented here enables the first successful catalytic carbon-heteroatom bond forming reaction of gem-diborylalkanes to form the corresponding α-aminoboronic acid derivatives, which are of great interest in medicinal and pharmaceutical chemistry.