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Catalytic Asymmetric Formal Total Synthesis of ( − )-Triptophenolide and (+)-Triptolide

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ABSTRACT

Abstract: Catalytic asymmetric formal synthesis of (−)-Triptophenolide and (+)-Triptolide have been achieved. Key reaction involves Palladium catalyzed asymmetric conjugate addition of aryl boronic acid to 3-methyl cyclohexe-1-none to form quaternary carbon. Claisen rearrangement and subsequent aldol reaction furnished trans-decaline key intermediate, which assured a formal total synthesis of (−)-Triptophenolide and (+)-Triptolide.

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Construction of quaternary stereocenter and overreacted rearrangement
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Sch2: Construction of quaternary stereocenter and overreacted rearrangement

Mentions: Our synthesis commenced with coupling reaction of arylboronic acid 8 [15]. Commercially available 3-Me-cyclohexenone was treated with trifluoroacetic palladium and (s)-t-BuPyOX ligand in heterogeneous solvent and 9 was isolated in moderate ee and 73 % yield [32]. The absolute configuration was determined accordingly [32]. Removal of Benzyl group by hydrogenation and allylation with allyl bromide afforded 6 as precursor of Claisen rearrangement. Treatment of 6 under microwave irradiation for 40 min gave rise to anticipated allyl phenol 11 as a minor product, together with tricyclic phenol 13 which was a product of Conia-ene reaction starting from 11 (Scheme 2). Unfortunately, attempts were failed to improve the yield of 11 by controlling reaction time and temperature. Alternative strategy need to be adopted to avoid side reactions.Scheme 2


Catalytic Asymmetric Formal Total Synthesis of ( − )-Triptophenolide and (+)-Triptolide
Construction of quaternary stereocenter and overreacted rearrangement
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5385656&req=5

Sch2: Construction of quaternary stereocenter and overreacted rearrangement
Mentions: Our synthesis commenced with coupling reaction of arylboronic acid 8 [15]. Commercially available 3-Me-cyclohexenone was treated with trifluoroacetic palladium and (s)-t-BuPyOX ligand in heterogeneous solvent and 9 was isolated in moderate ee and 73 % yield [32]. The absolute configuration was determined accordingly [32]. Removal of Benzyl group by hydrogenation and allylation with allyl bromide afforded 6 as precursor of Claisen rearrangement. Treatment of 6 under microwave irradiation for 40 min gave rise to anticipated allyl phenol 11 as a minor product, together with tricyclic phenol 13 which was a product of Conia-ene reaction starting from 11 (Scheme 2). Unfortunately, attempts were failed to improve the yield of 11 by controlling reaction time and temperature. Alternative strategy need to be adopted to avoid side reactions.Scheme 2

View Article: PubMed Central - PubMed

ABSTRACT

Abstract: Catalytic asymmetric formal synthesis of (−)-Triptophenolide and (+)-Triptolide have been achieved. Key reaction involves Palladium catalyzed asymmetric conjugate addition of aryl boronic acid to 3-methyl cyclohexe-1-none to form quaternary carbon. Claisen rearrangement and subsequent aldol reaction furnished trans-decaline key intermediate, which assured a formal total synthesis of (−)-Triptophenolide and (+)-Triptolide.

Graphical abstract"/>