Wednesday, October 17, 2012

(+)-Sch 725680


(+)-Sch 725680

Organic Letters, 2012, 14, 4303-4305

Toshifumi Takeuchi et al.

The retrosynthesis of (+)-Sch725680, begins with disconnecting the ester bond, thus giving acid chloride 13 and alcohol 10 as the main components.  Alcohol 10 comes from an hydroxyl addition on to a carbon-carbon triple bond in alkyne 9.  (Synthetically this is accomplished by just acidic treatment of the in-situ generated alcohol on the conjugated triple bond).  Compound 9 comes from an Aldol-condensation of ketone 8, which is generated by (a) alkyne lithium addition on aldehyde 6,; (b) methyl lithium attack on Weinreb amide portion of the molecule and finally,; (c) oxidation of the alcohol formed to the ketone functionality by using PCC.  Compound 6 comes by ring-opening of lactone 5 by N, O-dimethylhydroxylamine hydrochloride and oxidation of the primary alcohol.  The protected alcohol 5 comes from diol 4, which is formed by a cyclization of terminal alcohol on the chiral auxiliary 3.  Compound 3 is generated by a titanium mediated aldol reaction of imide 1 with aldehyde 2.

 

 

 

 

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