[4 + 2]-annulations of chiral organosilanes: Application to the total synthesis of leucascandrolide A.
Complete details of an asymmetric synthesis of leucascandrolide A (1) are described. The synthesis highlights the use of two diastereoselective [4 + 2]-annulations for the assembly of the functionalized bispyranyl macrolide 3. An efficient assembly and union of the oxazole-containing side chain 4 with macrolide 3 was carried out using a Mitsunobu reaction. A convergent route to the oxazole side chain was developed using a Sonogashira cross-coupling between 2-trifloyloxazole 16 and alkyne 17, which allowed for the installation of the C9'-C10' (Z)-olefin.
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Qibin
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Department of Chemistry and Center for Chemical Methodology and Library Development, Metcalf Center for Science and Engineering, 590 Commonwealth Avenue, Boston University, Boston, Massachusetts 02215, USA.
Dakin
Les A
LA
Panek
James S
JS
D000085:Acetates / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry; D000478:Alkylation; D000480:Alkynes / Q000737:chemistry; D004986:Ether / Q000737:chemistry; D007211:Indoles / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D018942:Macrolides / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry; D020005:Propanols / Q000737:chemistry; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D012821:Silanes / Q000737:chemistry; D013237:Stereoisomerism
D000085:Acetates; D000447:Aldehydes; D000475:Alkenes; D000480:Alkynes; D007211:Indoles; D007783:Lactones; D018942:Macrolides; D010080:Oxazoles; D020005:Propanols; D012717:Sesquiterpenes; D012821:Silanes; C511847:allylsilane; C408748:leucascandrolide A; D004986:Ether; C006463:allyl alcohol