Spirocyclohexanone

Tetracyclic or tricyclic cyclobutyl ketones with an iodide or a thiocarbonate group in the a-position of the 3-substituent give tricyclic or spirocyclohexanones on treatment with tributyltin hydride. 

Conversion of 3-cyano-4-stilbazole (69) into a tetrahydrocopyiine derivative illustrates the use of an alkenic group as the cation precursor (Scheme 35). Such processes are frequently less clear-cut for example, reaction of either the unsaturated nitrile (70) or oxime (71) resulted in competitive cycliza-tions to the minor Ritter product (72) and the major Hoesch product (73 Scheme 36). Similar competing processes have been observed for spirocyclohexanone oximes, but in other cases no cyclic products were produced at all. ... 

Chiral indole-2-sulfoxides have been employed by Feldman and Karatjas for asymmetric spirooxindole synthesis [70]. In one example, treatment of 115 with triflic anhydride initiated a Pummerer-type cyclization of the silyl enol ether side chain onto C3 (Scheme 30). Sequential hydrolysis of the resulting thioimidate intermediate with aqueous HgCl2 afforded the spirocyclohexanone functionalized oxindole 116 in modest yield and enantioselectivity at —78°C (33, 67% ee). Improved selectivity (58, 86% ee) was observed at lower reaction temperature (-110°C). 

The Thorpe-Ziegler reaction has been commonly used for the synthesis of spirocyclic ketones. An example of this comes from the work of Chande and coworkers in their efforts toward the synthesis of novel thiobarbituric acid derivatives. In this synthesis, 1,3-ditolylthiobarbituric acid 23 is reacted with acrylonitrile in the presence of sodamide in DMF at ambient temperature. Following successive Michael additions to produce 24, a spontaneous Thorpe-Ziegler cyclization occurs to provide enamine 25. Exhaustive hydrolysis and subsequent decarboxylation of 25 result in the desired spirocyclohexanone derivative 26. 

Sequences for the synthesis of the more complex discorhabdins, discorhabdin A and prianosin B, have been developed only in our laboratoiy. Discorhabdin A, which has a unique sulfur-containing fused ring structure, incorporating azacarbocyclic spirocyclohexanone and pyrroloiminoquinone systems, displays the most powerful cytotoxic activity among isolated members of the discorhabdin family. 

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