Protecting Group-Directed Diastereodivergent Synthesis of Chiral Tetrahydronaphthalene-Fused Spirooxindoles via Bifunctional Tertiary Amine Catalysis

Tetrodotoxin (TTX) is an indispensable probe in neuroscience, a biosynthetic and ecological enigma, and one of the most celebrated targets of synthetic chemistry. Here, we present a stereoselective synthesis of TTX that proceeds in 22 steps starting from a readily available glucose derivative. The central cyclohexane ring of TTX and its α-tertiary amine moiety was established via the intramolecular 1,3-dipolar cycloaddition of a nitrile oxide, followed by alkynyl addition to the resultant isoxazoline. After some carefully chosen protecting group manipulations, a ruthenium-catalyzed hydroxylactonization set the stage for the formation of its dioxa-adamantane core. Installation of the guanidine, oxidation of a primary alcohol, and late-stage epimerization of the resultant aldehyde gave a mixture of TTX and anhydro TTX. Our synthesis represents one of the most effective of TTX reported to date and could give ready access to biologically active derivatives.

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Sequential Au(i)/chiral tertiary amine catalysis: a tandem C–H functionalization of anisoles or a thiophene/asymmetric Michael addition sequence to quaternary oxindoles

Chemical Communications ◽

10.1039/c5cc10096h ◽

2016 ◽

Vol 52 (12) ◽

pp. 2537-2540 ◽

Cited By ~ 65

Author(s):

Zhong-Yan Cao ◽

Yu-Lei Zhao ◽

Jian Zhou

Keyword(s):

Tertiary Amine ◽

Michael Addition ◽

Enantioselective Synthesis ◽

Asymmetric Michael Addition ◽

Amine Catalysis

We report an unprecedented sequential Au(i)/bifunctional tertiary amine catalysis, which enables a tandem C–H functionalization of weak nucleophiles (anisoles or thiophenes) and asymmetric Michael addition for the highly enantioselective synthesis of quaternary oxindoles.

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Synthesis of Oxazolidinone and Tosyl Enamines by Tertiary Amine Catalysis

Synlett ◽

10.1055/s-0030-1259561 ◽

2011 ◽

Vol 2011 (05) ◽

pp. 699-701

Author(s):

Gabriel Fenteany ◽

Nicholas Eddy ◽

Peter Morse ◽

Martha Morton

Keyword(s):

Tertiary Amine ◽

Amine Catalysis

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Synergistic photoredox and tertiary amine catalysis: Generation of allylic sulfones from Morita-Baylis-Hillman acetates and sulfur dioxide

Organic Chemistry Frontiers ◽

10.1039/d1qo00344e ◽

2021 ◽

Author(s):

Xinhua Wang ◽

Ruixiu Liu ◽

Qiuping Ding ◽

Wei Xiao ◽

Jie Wu

Keyword(s):

Sulfur Dioxide ◽

Tertiary Amine ◽

Amine Catalysis

The first example for the synthesis of allylic sulfones through synergistic photoredox and tertiary amine catalysis, starting from MBH acetates, DABCO·(SO2)2 and 4-substituted Hantzsch esters or potassium alkyltrifluoroborates via a...

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Tertiary Amine Catalysis of the Reaction of Phenyl Isocyanate with Alcohols

The Journal of Organic Chemistry ◽

10.1021/jo01062a032 ◽

1961 ◽

Vol 26 (3) ◽

pp. 779-782 ◽

Cited By ~ 31

Author(s):

JOHN BURKUS

Keyword(s):

Tertiary Amine ◽

Phenyl Isocyanate ◽

Amine Catalysis

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Asymmetric sequential Au(i)/chiral tertiary amine catalysis: an enone-formation/cyanosilylation sequence to synthesize optically active 3-alkenyloxindoles from diazooxindoles

Chemical Communications ◽

10.1039/c6cc00333h ◽

2016 ◽

Vol 52 (20) ◽

pp. 3943-3946 ◽

Cited By ~ 38

Author(s):

Yu-Lei Zhao ◽

Zhong-Yan Cao ◽

Xing-Ping Zeng ◽

Jia-Meng Shi ◽

Yi-Hua Yu ◽

...

Keyword(s):

Tertiary Amine ◽

Optically Active ◽

Trimethylsilyl Cyanide ◽

Amine Catalysis

A gold-catalyzed enone-formation and asymmetric cyanosilylation sequence is developed, providing enantioenriched 3-alkenyloxindoles from diazooxindoles, furans and trimethylsilyl cyanide (TMSCN).

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