Site selectivity and stereocontrol remain major challenges in C–H bond functionalization chemistry, especially in linear aliphatic saturated hydrocarbon scaffolds. We report the highly enantioselective and site-selective catalytic borylation of remote C(sp3)–H bonds γ to the carbonyl group in aliphatic secondary and tertiary amides and esters. A chiral C–H activation catalyst was modularly assembled from an iridium center, a chiral monophosphite ligand, an achiral urea-pyridine receptor ligand, and pinacolatoboryl groups. Quantum chemical calculations support an enzyme-like structural cavity formed by the catalyst components, which bind the substrate through multiple noncovalent interactions. Versatile synthetic utility of the enantioenriched γ-borylcarboxylic acid derivatives was demonstrated.

α-Aminoboronic acids, isostructural boron analogues of α-amino acids, have received much attention because of the important biomedical applications implicated for compounds containing this structure. Additionally, the inherent versatility of α-aminoboronic acids as synthetic intermediates through diverse carbon−boron bond transformations makes the efficient synthesis of these compounds highly desirable. Here, we present a Rh-monophosphite chiral catalytic system that enables a highly efficient enantioselective borylation of N-adjacent C(sp 3 )−H bonds for a range of substrate classes including 2-(N-alkylamino)heteroaryls and Nalkanoyl-or aroyl-based secondary or tertiary amides, some of which are pharmaceutical agents or related compounds. Various stereospecific transformations of the enantioenriched α-aminoboronates, including Suzuki−Miyaura coupling with aryl halides and the Rh-catalyzed reaction with an isocyanate derivative of α-amino acid, affording a new peptide chain elongation method, have been demonstrated. As a highlight of this work, the borylation protocol was successfully applied to the catalyst-controlled site-selective and stereoselective C(sp 3 )−H borylation of an unprotected dipeptidic compound, allowing remarkably streamlined synthesis of the anti-cancer drug molecule bortezomib and offering a straightforward route for the synthesis of privileged molecular architectures.

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Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare type of lung cancer, accounting for 3% of all lung cancers. The prognosis is poor and the standard therapy has not been well established. Herein, we report a case of advanced LCNEC of the lung that responded to nivolumab. The patient was a 62-year old man with stage IVB LCNEC of the lung. The disease progressed following the administration of second-line chemotherapy, and he was treated with nivolumab 3 mg/kg as the third-line treatment. Although treatment was ceased after two cycles due to interstitial pneumonia, the disease remained stable for approximately six months under observation. There was no other adverse event related to nivolumab. Following patient mortality from tumor progression, PD-L1 expression was observed to be negative (tumor proportion score <1%) by a re-examination of the primary biopsy specimen. The case herein suggests that nivolumab may be a possible treatment option for LCNEC.

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