RhIII-Catalyzed Synthesis of Isoquinolones and 2-Pyridones via Annulation of N-Methoxyamides and Nitroalkenes.

The Rh(III)-catalyzed synthesis of 4-substituted isoquinolones and 2-pyridones by the annulation of N-methoxyamides and nitroalkenes has been developed. Both aliphatic and aromatic nitroalkenes were effective inputs. Annulations also proceeded for aromatic, alkenyl, and heteroaromatic C-H bond starting materials. Moreover, benzoic acid provided a novel nitrodihydroisocoumarin. The structure and relative stereochemistry of this compound, which is an oil at room temperature, was determined unambiguously by single crystal X-ray diffraction of its inclusion complex with a hydrogen-bonded host framework.

α-Branched amines by catalytic 1,1-addition of C-H bonds and aminating agents to terminal alkenes.

α-Branched amines are present in hundreds of pharmaceutical agents and clinical candidates and are important targets for synthesis. Here we show the convergent synthesis of α-branched amines from three readily accessible starting materials: aromatic C-H bond substrates, terminal alkenes, and aminating agents. This reaction proceeds by an intermolecular formation of C-C and C-N bonds at the sp 3 carbon branch site through an uncommon 1,1-alkene addition pathway. The reaction is carried out under mild conditions and has high functional group compatibility. Ethylene and propylene feedstock chemicals are effective alkene inputs with ethylene in particular providing for the one step synthesis of α-methyl branched amines, a motif prevalent in drug structures. The reaction is scalable, and 1% loading of an air stable dimeric rhodium precatalyst is effective for several different types of products. The use of chiral catalysts also enables the asymmetric synthesis of α-branched amines.

Total Synthesis of (+)-Pancratistatin by the Rh(III)-Catalyzed Addition of a Densely Functionalized Benzamide to a Sugar-Derived Nitroalkene.

Herein, we report the concise total synthesis of (+)-pancratistatin, accessed in a 10-step linear sequence from commercially available inputs. The convergent synthesis features a highly diastereoselective Rh(III)-catalyzed C-H bond addition to a d-glucose-derived nitroalkene and a late-stage intramolecular transamidation to furnish the B ring lactam.

Rh(III)-Catalyzed Aryl and Alkenyl C-H Bond Addition to Diverse Nitroalkenes.

The transition metal catalyzed C-H bond addition to nitroalkenes has been developed. Very broad nitroalkene scope was observed for this Rh(III)-catalyzed method, including for aliphatic, aromatic and ß,ß-disubstituted derivatives. Additionally, various directing groups and both aromatic and alkenyl C-H bonds were effective in this transformation. Representative nitroalkane products were converted to dihydroisoquinolones and dihydropyridones in a single step and in high yield by iron mediated reduction and in situ cyclization. Moreover, preliminary success in enantioselective Rh(III)-catalyzed C-H bond addition to nitroalkenes was achieved as was X-ray structural characterization of a nitronate intermediate.

Rh(III)-Catalyzed C-H Bond Addition/Amine-Mediated Cyclization of Bis-Michael Acceptors.

A Rh(III)-catalyzed C-H bond addition/primary amine-promoted cyclization of bis-Michael acceptors is reported. The C-H bond addition step occurs with high chemoselectivity, and the subsequent intramolecular Michael addition, mediated by a primary amine catalyst, sets three contiguous stereocenters with high diastereoselectivity. A broad range of directing groups and both aromatic and alkenyl C-H bonds were shown to be effective in this transformation, affording functionalized piperidines, tetrahydropyrans, and cyclohexanes.

Elastofibroma: the initial report in the oral mucosa.

Elastofibroma is a well known pseudotumorous process that characteristically occurs in the scapular region in the presence of trauma or injury. Additionally, numerous other sites of origin have been reported in the literature, but to date none have presented in the oral cavity. A 56-year-old female presented with a painless small mass in the floor of the mouth. A longstanding history of trauma to the region was noted. Histopathologic examination revealed the mass to be comprised of a haphazard array of collagen and elastic fibers in a myxomatous background. The elastic nature of the fibers was confirmed by an elastic stain. The diagnosis of elastofibroma was rendered based upon the microscopic findings. This represents the first reported case of elastofibroma of the oral cavity.

Oral malignancies associated with negative transepithelial brush biopsy.

PURPOSE: This study was performed to assess the incidence of negative brush biopsy for oral lesions later demonstrated histologically to be squamous cell carcinoma. METHODS: All diagnoses of oral squamous cell carcinoma from a university oral pathology service for the period June 2000 through March 2002 were reviewed to determine if any had previously undergone brush biopsy reported to be "negative for epithelial abnormality." Those cases identified were further investigated to determine the time lapse between brush biopsy and definitive tissue diagnosis. RESULTS: Four cases of brush biopsy negative squamous cell carcinoma were identified from 115 total cases of malignancy (3.5%). The average time from brush biopsy to tissue diagnosis was 117.25 days (range, 5 to 292 days). CONCLUSION: False negative reports are possible with the oral brush biopsy technique. Persistent lesions should undergo tissue biopsy for definitive diagnosis.