Total synthesis of (+)-isatisine a: application of a silicon-directed mukaiyama-type [3 + 2]-annulation.
Complete details of an asymmetric synthesis of (+)-isatisine A (1) are described. The synthesis highlights the use of a highly diastereoselective Mukaiyama-type [3 + 2]-annulation of allylsilane 5 with the unsaturated aldehyde 9a to assemble the functionalized tetrahydrofuran core of isatisine A. A convergent route to the framework of the natural product was established that employed a substrate-controlled indole coupling that was followed by a late-stage intramolecular copper(I)-mediated amidation to complete the assembly of the tetracyclic framework of (+)-isatisine A. In addition, the scope of the [3 + 2]-annulation was evaluated and enhanced utilizing diastereomeric allylsilanes anti-5 and syn-5 to establish an efficient route to stereochemically well-defined tetrahydrofurans.
Department of Chemistry and Center for Chemical Methodology and Library Development, Metcalf Center for Science and Engineering, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, United States.
Jihoon
J
Lee
Department of Chemistry and Center for Chemical Methodology and Library Development, Metcalf Center for Science and Engineering, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, United States.
James S
JS
Panek
D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D007510:Isatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D012821:Silanes / Q000737:chemistry*; D013237:Stereoisomerism
D026121:Indole Alkaloids; D012821:Silanes; C524145:isatisine A; D007510:Isatin