Alotaketal A

 

Alotaketal A

Organic Letters 2012, 14, 5492-5494

M. Xuan, I. Paterson, S. M. Dalby *

The retrosyntheses of Alotaketal A begins with a sequence of double oxidation of two alcohols (a primary and the other secondary) and then selective reduction of the aldehyde in presence of the ketone by using sodium triacetoxyborohydride.  This is a bold final step!  Compound 16 has the sensitive ketal group which is formed by internal cyclization and protection of compound 15.  The allylic alcohol in 15 is formed by the nucleophilic attack of lithiated 6 on lactone 14.  Lactone 14 is formed by an intermolecular HWE reaction of phosphonate 13, which comes by the coupling of acid chloride of 12 with alcohol 11.  Here, the Yamaguchi reagent (trichlorobenzoyl chloride) was used to activate the acid.  Compound 11 was prepared by the selective Johnson-Lemieux oxidation of the less-hindered alkene bond of compound 10.  Compound 10 was derived by an interesting allylic oxidation and then selective reduction procedure.  The allylic alcohol 9 gets oxidized to the ketone (at the unsaturated carbon) with simultaneous dehydration to give an a,b-unsaturated ketone (not drawn).  This is then stereoselectively reduced to the allylic alcohol 10 by using the bulky L-selectride.  The protected TBS ether in 9 came from by the reduction (and then protection) of ketone 8.  This a-hydroxyketone was prepared by Rubbotom oxidation of ketone 7 (7 was first converted to its TMS enol ether and then oxidized by using mCPBA).  Compound 7 was prepared from (R)-carvone by first chlorinating the allylic carbon (Ca(OCl)₂), then hydrolyzing it to the alcohol and then protecting it as TIPS-ether.

The intermediate 6 has the allylic iodide group, which came from the corresponding ester 5.  Ester 5 was treated with TMSCH₂MgCl which gave the double addition of the “CH₂-“ group on the ester.  It also produced a tertiary alcohol which eliminated.  Ester 5 came from a Nagao aldol reaction of chiral auxially 3 with aldehyde 2.  Aldehyde 2 is simply the oxidized form of geraniol – but it was produced in a rather round-about way.  Geraniol was first chlorinated and then reduced by LAH.  The allyl group was then oxidized to the aldehyde by MnO₂.