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

A copper-catalysed regio- and diastereoselective borylamination of α,β-unsaturated esters with B2pin2 and hydroxylamines has been developed to deliver acyclic β-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 β-borylated α-amino acids. The products can be stereospecifically transformed into β-functionalised α-amino acids, which are of potent interest in medicinal chemistry.Nishino S., Nishii Y., Hirano K.. anti-Selective synthesis of β-boryl-α-amino acid derivatives by Cu-catalysed borylamination of α,β-unsaturated esters. Chemical Science 13, 14387 (2022); https://doi.org/10.1039/d2sc06003e

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.Nishino S., Hirano K., Miura M.. Copper-Catalyzed Electrophilic Amination of gem-Diborylalkanes with Hydroxylamines Providing α-Aminoboronic Acid Derivatives. Organic Letters. 21(12), 4759-4762, (2019), 21 June 2019; © 2019 American Chemical Society. https://doi.org/10.1021/acs.orglett.9b01640

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.This is the accepted version of the following article: Nishino S., Hirano K., Miura M.. Cu-Catalyzed Reductive gem-Difunctionalization of Terminal Alkynes via Hydrosilylation/Hydroamination Cascade: Concise Synthesis of α-Aminosilanes. Chemistry - A European Journal 26, 8725 (2020), which has been published in final form at https://doi.org/10.1002/chem.202001799. This article may be used for non-commercialpurposes in accordance with the Wiley Self-ArchivingPolicy [https://authorservices.wiley.com/author-resources/Journal-Authors/licensing/self-archiving.html

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 β-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.Nishino S., Miura M., Hirano K.. An umpolung-enabled copper-catalysed regioselective hydroamination approach to α-amino acids. Chemical Science 12, 11525 (2021); https://doi.org/10.1039/d1sc03692k

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

A copper-catalyzed silylamination of α,β-unsaturated esters with silylboranes and hydroxylamines has been developed to afford the corresponding β-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 β-silyl-α-amino acids with synthetically acceptable diastereomeric ratios (55:45-82:18 dr) and high enantiomeric ratios (81:19-99:1 er).Kobayashi T., Nishino S., Miura M., et al. Synthesis of β-Silyl-α-amino Acid Derivatives by Cu-Catalyzed Regio- and Enantioselective Silylamination of α,β-Unsaturated Esters. Organic Letters. 24(6), 1418-1422, (2022), 18 February 2022; © 2022 American Chemical Society. https://doi.org/10.1021/acs.orglett.2c00309

Copper-Catalyzed Regio- and Diastereoselective Borylacylation of α,β-Unsaturated Esters

A copper-catalyzed regio- and diastereoselective borylacylation of α,β-unsaturated esters with B2pin2 and acyl fluorides has been developed to afford the β’-boryl-β-ketoesters with high anti-diastereoselectivity (up to >99 : 1). Additionally, the borylcarbamoylation is possible by using isocyanates as electrophiles instead of acyl fluorides. Moreover, the enantioselective borylacylation and borylcarbamoylation are also achieved by judicious choice of a chiral phosphoramidite-ligated copper complex.This is the peer reviewed version of the following article: Nishino S., Hirano K.. Asian Journal of Organic Chemistry. 2023, 2, e202200610 which has been published in final form at https://doi.org/10.1002/ajoc.202200636. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited

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

A copper-catalyzed regioselective hydroamination of α,β-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.Nakamura S., Nishino S., Hirano K.. Synthesis of α-Aminophosphonates by Umpolung-Enabled Cu-Catalyzed Regioselective Hydroamination. Journal of Organic Chemistry. 88(2), 1270-1281, 20 January 2023; © 2023 American Chemical Society. https://doi.org/10.1021/acs.joc.2c02632

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

This is the accepted version of the following article: Nishino S., Hirano K., Miura M.. Cu-Catalyzed Reductive gem-Difunctionalization of Terminal Alkynes via Hydrosilylation/Hydroamination Cascade: Concise Synthesis of α-Aminosilanes. Chemistry - A European Journal 26, 8725 (2020), which has been published in final form at https://doi.org/10.1002/chem.202001799. This article may be used for non-commercialpurposes in accordance with the Wiley Self-ArchivingPolicy [https://authorservices.wiley.com/author-resources/Journal-Authors/licensing/self-archiving.html]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

Preparation and Use of (γ,γ-Dioxyallyl)boronates

A copper-catalyzed stereoselective 1,4-acylboration of α,β- unsaturated esters with B2pin2 and pivalic anhydride has been developed to afford the corresponding (E)-allylboronates with two distinct oxygenated functionalities at the γ positions, which are difficult to prepare by other means. The chemoselective post functionalizations of Bpin and pivalate moieties in the product are also demonstrated.This is an Accepted Manuscript of an article published by Thieme Publishing Group in Journal Title on Publication Date, available online at https://doi.org/10.1055/a-2051-1054

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

Inoue T., Nishino S., Yasui K., et al. Nickel-Catalyzed Electrophilic Amination of the Biphenylene C-C σ-Bond. Organic Letters 26, 4268 (2024); https://doi.org/10.1021/acs.orglett.4c01226.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