Hydrophosphination of Bicyclo[1.1.0]butane-1-carbonitriles

Hydrophosphination of bicyclo[1.1.0]­butyl nitriles with phosphine boranes and phosphites provided novel cyclobutyl-P derivatives. The reaction generally favors the <i>syn</i>-diastereomer, and the nitrile can be reduced and converted to other functional groups, thus enabling the preparation of bidentate ligands that access new conformational space by virtue of their attachment to the torsionally malleable but sterically restrictive cyclobutane scaffold. The enantioselective hydrogenation of dehydrophenylalanine using a bidentate phosphine–phosphite ligand illustrates the synthetic utility of the newly prepared scaffold

Asymmetric Oxidation of a Dihydrothienopyrimidine

A robust catalytic asymmetric oxidation of prochiral sulfide <b>1</b> has been achieved by the use of a chiral titanium–hydrobenzoin complex. Reproducible reaction conditions were identified by screening reaction parameters and DOE optimization. The enantioselectivity was found to be mostly influenced by the amount of water and the time the catalyst was aged before addition of the sulfide

Ligand-Enabled γ‑C(sp³)–H Activation of Ketones

We report the first example of Pd­(II)-catalyzed γ-C­(sp³)–H activation of ketones directed by a practical 2,2-dimethyl aminooxyacetic acid auxiliary. 2-Pyridone ligands are identified to enable C­(sp³)–H activation for the first time. A rare six-membered palladacycle intermediate is isolated and characterized to elucidate the reaction mechanism. Both (hetero)­arylation and vinylation of γ-C­(sp³)–H bonds are demonstrated. Sequential β- and γ-C­(sp³)–H (hetero)­arylation of muscone showcases the utility of this method for late-stage diversification. A convenient Mn­(II)-catalyzed auxiliary removal is also developed to further underscore the practicality of this transformation

Ligand-Enabled γ‑C(sp³)–H Activation of Ketones

We report the first example of Pd­(II)-catalyzed γ-C­(sp³)–H activation of ketones directed by a practical 2,2-dimethyl aminooxyacetic acid auxiliary. 2-Pyridone ligands are identified to enable C­(sp³)–H activation for the first time. A rare six-membered palladacycle intermediate is isolated and characterized to elucidate the reaction mechanism. Both (hetero)­arylation and vinylation of γ-C­(sp³)–H bonds are demonstrated. Sequential β- and γ-C­(sp³)–H (hetero)­arylation of muscone showcases the utility of this method for late-stage diversification. A convenient Mn­(II)-catalyzed auxiliary removal is also developed to further underscore the practicality of this transformation

Distal Stereocontrol Using Guanidinylated Peptides as Multifunctional Ligands: Desymmetrization of Diarylmethanes via Ullman Cross-Coupling

We report the development of a new class of guanidine-containing peptides as multifunctional ligands for transition-metal catalysis and its application in the remote desymmetrization of diarylmethanes via copper-catalyzed Ullman cross-coupling. Through design of these peptides, high levels of enantioinduction and good isolated yields were achieved in the long-range asymmetric cross-coupling (up to 93:7 er and 76% yield) between aryl bromides and malonates. Our mechanistic studies suggest that distal stereocontrol is achieved through a Cs-bridged interaction between the Lewis-basic <i>C</i>-terminal carboxylate of the peptides with the distal arene of the substrate

Solvent-Free Methallylboration of Ketones Accelerated by <i>tert</i>-Alcohols

A solvent- and metal-free process has been developed for the direct methallylboration of ketones employing the stable <i>B</i>-methallylborinane <b>1</b>, which was accelerated by tertiary alcohols. In the presence of 2.0 equiv of readily available tertiary alcohols such as <i>tert</i>-amyl alcohol, the methallylation products were prepared at room temperature in excellent yields. The salient features of the described process include simple operation, high efficiency, and mild reaction conditions

Tunable <i>P</i>‑Chiral Bisdihydrobenzooxaphosphole Ligands for Enantioselective Hydroformylation

Air-stable and tunable chiral bisdihydrobenzooxaphosphole ligands (BIBOPs) were employed in rhodium-catalyzed asymmetric hydroformylation of various terminal olefins with excellent conversions (>99%), moderate-to-excellent enantioselectivities (up to 95:5 er), and branched to linear ratios (b:l) of up to 400

Metal-Free Cycloetherification by in Situ Generated <i>P</i>‑Stereogenic α‑Diazanium Intermediates: A Convergent Synthesis of Enantiomerically Pure Dihydrobenzooxaphospholes

A metal-free tandem reaction, initiated by the generation of a diazonium cation and followed by cycloetherification, was developed. Acid-promoted de-<i>tert</i>-butylation of <i>N</i>-nitroso <i>N</i>-<i>tert</i>-butylamine was used to generate a diazonium cation in situ, demonstrating a new application of nitroso chemistry. This reaction was employed in the synthesis of substituted benzofuran-3­(2<i>H</i>)-ones and dihydrobenzo­[<i>d</i>]­[1,3]­oxaphosphole 3-oxides

The Reaction of Grignard Reagents with Bunte Salts: A Thiol-Free Synthesis of Sulfides

S-Alkyl, S-aryl, and S-vinyl thiosulfate sodium salts (Bunte salts) react with Grignard reagents to give sulfides in good yields. The S-alkyl Bunte salts are prepared from odorless sodium thiosulfate by an S_N2 reaction with alkyl halides. A Cu-catalyzed coupling of sodium thiosulfate with aryl and vinyl halides was developed to access S-aryl and S-vinyl Bunte salts. The reaction is amenable to a broad structural array of Bunte salts and Grignard reagents. Importantly, this route to sulfides avoids the use of malodorous thiol starting materials or byproducts

Versatile Alkylation of (Hetero)Aryl Iodides with Ketones via β‑C(sp³)–H Activation

We report Pd­(II)-catalyzed β-C­(sp³)–H (hetero)­aryl­ation of a variety of ketones using a commercially available 2,2-dimethyl amino­oxy­acetic acid auxiliary. Facile installation and removal of the auxiliary as well as its superior scope for both ketones and (hetero)­aryl iodides overcome the significant limitations of the previously reported β-C­(sp³)–H arylation of ketones. The ready availability of ketones renders this reaction a broadly useful method for alkyl–(hetero)­aryl coupling involving both primary and secondary alkyls