Oxindole-3-lactone

Wang, X.-N., Zhang, Y.-Y, Ye, S. (2010). Enantioselective synthesis of spirocyclic oxindole-(3-lactones via n-heterocyclic carbene-catalyzed cycloaddition of ketenes and isatins. Advanced Synthesis Catalysis, 352, 1892-1895. 

The synthesis13 of the pentacyclic intermediate (10) constitutes a second formal synthesis of ( )-tryptoquivaline G, since (10) has already been converted into tryptoquivaline G by Biichi et al.14a The most noteworthy stages in the synthesis of (10) (Scheme 1) involved the oxidation of the indolepropionic acid derivative (11) by means of thallium trinitrate, which gave the oxindole-lactone (12), and the oxidative removal of the unwanted methyl group in (12) by means of selenium dioxide.13... 

An independent synthesis of the spirocyclic oxindole-lactone (20) constitutes a second formal synthesis of ( )-trypto-... 

In 2012, Scheldt and coworkers developed the enantioselective [3 + 2] an-nulation of enals and isatins under NHC/Lewis acid cooperative catalysis. Both electron-withdrawing and electron-donating groups were tolerated, furnishing the spiro-oxindole lactones 56 in good yields and with high enantioselectivities. The spiro-oxindole lactone was converted into maremycin B in five steps and in 17% overall yield (Scheme 20.27). 

Spiro oxindole lactones are obtained enantioselectively by [3 + 2] addition of a,/0-unsaturated aldehydes to isatins catalysed by an NHC. The diastereo- and enantio-selectivities are enhanced by a Lewis acid (LiCl) bidentate coordination with the isatin oxygens. ... 

The easy condensation of aldehydes with 3-monosubstituted oxindoles has been further exploited by Ban and co-workers, who synthesized several 3-spirooxindole derivatives 48). The approach was used in the stereospecific synthesis of racemic iV-methylrhynchophyllane (Chart X). The Iraws-diethylcyclopentanone CVIIIa was subjected to Baeyer-Villiger oxidation to yield the threo lactone CIX, which was converted to the chloroaldehyde CXI, by successive reaction with phosphorus... 

The group subsequently found that trifloromethyl ketones and isatins were suitable electrophiles for the NHC-catalysed [2 + 2] cycloaddition reaction of ketenes, ° giving the eorresponding trifluoromethyl-substituted p-lactones 165 and spiroeyelie oxindole-p-laetones 167, respectively, in good yields with high enantioselectivities (Scheme 20.69). 

A mechanistic rationalization for this reaction is presented in Scheme 5.48. Domino process is initiated with generation of key intermediate 152, which undergoes a 1,4-addition of a deprotonated oxindole to form 153. After H-migration and following aldol reaction with another molecule of alkynyl aldehyde, intermediate 155 is formed. Subsequent lactonization delivers prodnct 66 and regenerates NHC for the next catalytic cycle. The stereochemistry of the products may be determined by the most sterically favored chair transition state in 155. 

Cao, T., Linton, E. C., Deitch, J., Berritt, S., Kozlowski, M. C. (2012). Copper(ll)-and Palladium(ll)-catalyzed enantioselective Claisen Rearrangement of allyloxy- and propargyloxy-indoles to quaternary oxindoles and spirocyclic lactones. Journal of Organic Chemistry, 77, 11034-11055. 

Later, Ye and coworkers developed a highly enantioselective synthesis of spiro-cyclic oxindole-p-lactones by a [2-1-2] cycloaddition reaction between isatins and ketenes catalyzed by A-heterocyclic carbenes (NHCs) [57]. TheA-methyl isatin 54c reacted with various aromatic ketenes 100 in the presence of an NHC precursor XXVI at -40 °C to afford the corresponding spirocyclic oxindole-p-lactones 101 in good yields and enantioselectivities, as shown in Scheme 10.36. 

X. Huang, J. Peng, L. Donga, Y.-C. Chen, Asymmetric assembly of 2-oxindole and a-angelica lactone units to construct vicinal quaternary chiral centers, Chem. Commun. 48 (2012) 2439-2441. 

Following this pioneering work, other metals with various chiral ligands were added to the list of successful systems able to catalyze electrophilic fluorination on a wide range of substrates in particular, this includes Pd, Ni, Cu, Zn, and Ru catalysts. Indeed, efficient enantioselective fluo-rinations of various p-keto esters, oxindoles, rcrt-butoxy-carbonyl lactones and lactams, and p-keto phosphonates... 

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