Stereoselective Synthesis of Bicyclo[6.1.0]nonene Precursors of the Bioorthogonal Reagents s‑TCO and BCN

The cyclooctyne BCN and the <i>trans-</i>cyclooctene s-TCO are widely used in bioorthogonal chemistry. A bottleneck for their synthesis had been a poorly selective cyclopropanation with ethyl diazoacetate. Here, we describe that low catalyst loadings (0.27 mol %) of Rh₂(<i>S</i>-BHTL)₄ provide the BCN precursor with 79:21 <i>syn</i>/<i>anti</i> selectivity. The synthesis of the s-TCO precursor was best achieved through a sequence of Rh₂(OAc)₄ (0.33 mol %)-catalyzed cyclopropanation, followed by ester hydrolysis under epimerizing conditions. Both sequences could be carried out on multigram scale

Stereoselective Synthesis of Bicyclo[6.1.0]nonene Precursors of the Bioorthogonal Reagents s‑TCO and BCN

The cyclooctyne BCN and the <i>trans-</i>cyclooctene s-TCO are widely used in bioorthogonal chemistry. A bottleneck for their synthesis had been a poorly selective cyclopropanation with ethyl diazoacetate. Here, we describe that low catalyst loadings (0.27 mol %) of Rh₂(<i>S</i>-BHTL)₄ provide the BCN precursor with 79:21 <i>syn</i>/<i>anti</i> selectivity. The synthesis of the s-TCO precursor was best achieved through a sequence of Rh₂(OAc)₄ (0.33 mol %)-catalyzed cyclopropanation, followed by ester hydrolysis under epimerizing conditions. Both sequences could be carried out on multigram scale

Enantioselective Synthesis of Cyclobutanes via Sequential Rh-catalyzed Bicyclobutanation/Cu-catalyzed Homoconjugate Addition

Enantiomerically enriched cyclobutanes are constructed by a three-component process in which <i>t</i>-butyl (<i>E</i>)-2-diazo-5-arylpent-4-enoates are treated with Rh₂(<i>S</i>-NTTL)₄ to provide enantiomerically enriched bicyclobutanes, which can subsequently engage in homoconjugate addition/enolate trapping sequence to give densely functionalized cyclobutanes with high diastereoselectivity. This three-component, two-catalyst procedure can be carried out in a single flask. Rh₂(<i>S</i>-NTTL)₄-catalyzed reaction of <i>t</i>-butyl (<i>Z</i>)-2-diazo-5-phenylpent-4-enoate gives the Büchner cyclization product in excellent enantioselectivity

Enantioselective Synthesis of Cyclobutanes via Sequential Rh-catalyzed Bicyclobutanation/Cu-catalyzed Homoconjugate Addition

Enantiomerically enriched cyclobutanes are constructed by a three-component process in which <i>t</i>-butyl (<i>E</i>)-2-diazo-5-arylpent-4-enoates are treated with Rh₂(<i>S</i>-NTTL)₄ to provide enantiomerically enriched bicyclobutanes, which can subsequently engage in homoconjugate addition/enolate trapping sequence to give densely functionalized cyclobutanes with high diastereoselectivity. This three-component, two-catalyst procedure can be carried out in a single flask. Rh₂(<i>S</i>-NTTL)₄-catalyzed reaction of <i>t</i>-butyl (<i>Z</i>)-2-diazo-5-phenylpent-4-enoate gives the Büchner cyclization product in excellent enantioselectivity

Enantioselective Synthesis of Cyclobutanes via Sequential Rh-catalyzed Bicyclobutanation/Cu-catalyzed Homoconjugate Addition

Enantiomerically enriched cyclobutanes are constructed by a three-component process in which <i>t</i>-butyl (<i>E</i>)-2-diazo-5-arylpent-4-enoates are treated with Rh₂(<i>S</i>-NTTL)₄ to provide enantiomerically enriched bicyclobutanes, which can subsequently engage in homoconjugate addition/enolate trapping sequence to give densely functionalized cyclobutanes with high diastereoselectivity. This three-component, two-catalyst procedure can be carried out in a single flask. Rh₂(<i>S</i>-NTTL)₄-catalyzed reaction of <i>t</i>-butyl (<i>Z</i>)-2-diazo-5-phenylpent-4-enoate gives the Büchner cyclization product in excellent enantioselectivity