Interrupted Carbonyl‐Alkyne Metathesis

Carbonyl‐olefin metathesis and carbonyl‐alkyne metathesis represent established reactivity modes between carbonyls, alkenes, and alkynes under Lewis and Brønsted acid catalysis. Recently, an interrupted carbonyl‐olefin metathesis reaction has been reported that results in tetrahydrofluorenes via a distinct fragmentation of the reactive intermediate. We herein report the development of an analogous transformation interrupting the carbonyl‐alkyne metathesis reaction path resulting in dihydrofluorene products relying on Lewis acidic superelectrophiles as active catalytic species.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153682/1/adsc201901358.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153682/2/adsc201901358_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153682/3/adsc201901358-sup-0001-misc_information.pd

Synthesis and Biological Evaluation of the Antimicrobial Natural Product Lipoxazolidinone A

The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogs to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization

Chiral Tetrahydropyridines via FeCl3-Catalyzed Carbonyl-Olefin Metathesis

Herein, we describe the application of Lewis acid-catalyzed carbonyl-olefin metathesis towards the synthesis of chiral, substituted tetrahydropyridines from commercially available amino acids as chiral pool reagents. This strategy relies on FeCl3 as an inexpensive and environmentally benign catalyst and enables access to a variety of substituted tetrahydropyridines under mild reaction conditions. The reaction proceeds with complete stereoretention and is viable for a variety of natural and unnatural amino acids to provide the corresponding tetrahydropyridines in up to 99% yield. <br /

Hydrazone and Oxime Olefination via Ruthenium Alkylidenes

We describe the development of an efficient method for the olefination of hydrazones and oximes. The key design approach that enables this transformation is tuning of the energy/polarity of C=N π-bonds by employing heteroatom functionalities (NR2, OR). The resulting hydrazones or oximes facilitate olefination with ruthenium alkylidenes. Through this approach, we show that air-stable, commercially available ruthenium alkylidenes provide access to functionalized alkenes (20 examples) in ring-closing reactions with yields up to 88 %.Olefination of carbon–heteroatom double bonds is a powerful approach to access highly functionalized olefins. An approach is reported here that uses air-stable and commercially available ruthenium alkylidenes to promote C=N/olefin ring closure. The enabling strategy for this reaction is the use of hydrazones and oximes as readily accessible substrates that preferentially react with ruthenium alkylidenes, even in the presence of carbonyl groups.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/172859/1/anie202112101-sup-0001-misc_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172859/2/anie202112101_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172859/3/anie202112101.pd

Hydrazone and Oxime Olefination via Ruthenium Alkylidenes

We describe the development of an efficient method for the olefination of hydrazones and oximes. The key design approach that enables this transformation is tuning of the energy/polarity of C=N π-bonds by employing heteroatom functionalities (NR2, OR). The resulting hydrazones or oximes facilitate olefination with ruthenium alkylidenes. Through this approach, we show that air-stable, commercially available ruthenium alkylidenes provide access to functionalized alkenes (20 examples) in ring-closing reactions with yields up to 88 %.Olefination of carbon–heteroatom double bonds is a powerful approach to access highly functionalized olefins. An approach is reported here that uses air-stable and commercially available ruthenium alkylidenes to promote C=N/olefin ring closure. The enabling strategy for this reaction is the use of hydrazones and oximes as readily accessible substrates that preferentially react with ruthenium alkylidenes, even in the presence of carbonyl groups.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/172797/1/ange202112101-sup-0001-misc_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172797/2/ange202112101_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172797/3/ange202112101.pd

Synthesis and Biological Evaluation of the Antimicrobial Natural Product Lipoxazolidinone A

The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogs to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization