(-)-KAITOCEPHALIN

 

 

(-)-KAITOCEPHALIN

Organic Letters, 2012, 14, 1644-1647

K. Takahashi, D. Yamaguchi, J. Ishihara, S. Hatakeyama*

The retrosythesis of (-)-Kaitocephalin begins with unmasking all the acid groups by oxidizing phenyl and carbon-carbon double bonds while the amino and alcohol groups are also simultaneously generated by deprotecting the oxazolidone ring of 14.  This is very rarely seen in total syntheses as people generally shy away from such strong oxidations towards the end of the synthesis.  So, keeping a benzene ring and carbon-carbon double bonds are “masked acids” is a useful disconnection.  Compound 14 predictably comes from acid chloride 13 and deprotected form of amine 12.  Compound 12 is formed by a stereoselective intramolecular C-H amination in 11 mediated by a Rh catalyst.   This is a neat way of establishing a crucial stereocenter.  Compound 11 comes from protected alcohol 10.  Compound 10 is generated by an intramolecular addition of a carbamate on cyclic sulfamate 9, which comes from another stereoselective intramolecular C-H amination of sulfonamide 8.  This step is very similar to the preparation of 12 from 11 – sulfonyl versus and carbonyl and also a different ligand is used in the Rh catalyst.  Compound 8 comes from protected alcohol 7, which in turn is prepared by a Overman rearrangement reaction of alcohol 6.  This step establishes the quaternary spiro stereocenter.  Compound 6 is formed by a Suzuki reaction between alkyl boronate ester and vinyl iodide 5.  This comes from protection-deprotection of alcohol 4 whose precursor is ketone 3.  Ketone 3 comes from the iodination of 2, which is derived from alcohol 1, by an enzyme-mediated stereoselective oxidation.