Oxidative spirocyclization

The final, critical oxidative spirocyclization of the 2,3-disubstituted indole to the spiro oxindole was effected by treatment of 124 with tert-butyl hypochlorite in pyridine to provide the labile 125 [Fig. (34)]. The Pinacol-type rearrangement was conducted by treating compound 125 with p-toluenesulfonic acid in THF/water. It is assumed that the chlorination of 124 proceeds from the least hindered face of the indole, to give the a-chloroindolene 125. The hydration of the imine functionality must also occur from the same a-face that is syn to the relatively large chlorine atom furnishing the syn-chlorohydrin 126, that subsequently rearranges stereospecifically to the desired spiro oxindole 127. 

The other key step in the synthetic approaches to FR901483 is the elaboration of the quaternary spirocenter at C(l) (Scheme 4). Sorensen, Ciufolini, and Wardrop all use an oxidative spirocyclization of nitrogen tethered phenol derivatives, employing hypervalent iodine reagents, to generate the spirocenter at C(l). In contrast, in the other approaches the formation of the quaternary stereocenter does not coincide with the... 

First, on the basis of the hypothesis by Munro and co-workers shown in Scheme 1, we examined the biosynthetically plausible route from makaluvamine F using our previously developed oxidative spirocyclization reaction with PIFA. As a result, the oxidative cyclization of makaluvamine F as well as the trimethylsily-lated makaluvamine F using PIFA under various conditions yielded a complex mixture, probably due to the high reactivity of the iodine(III) reagent toward the sulfide (Scheme 28). 

The oxidation of phenolic substrates in the intramolecular mode has been widely exploited as a powerful synthetic tool for the construction of a spirodienone fragment. Numerous oxidative spirocyclizations of phenolic substrates containing an internal oxygen, nitrogen, or carbon nucleophile have been reported and utilized in natural product syntheses. Representative examples of spirocyclizations employing oxygen-based internal nucleophiles are shown below in Schemes 3.98-3.102. 

The oxidative spirocyclization of phenolic substrates containing an internal nitrogen nucleophile provides a useful tool for the construction of nitrogen heterocycles [287, 315-318], For example, the hypervalent iodine-induced cyclization of phenolic oxazolines 251 affords the synthetically useful spirolactam products... 

Hypervalent iodine induced oxidative dearomatization of orf/io-substituted phenolic substrates in the intramolecular mode has been realized as an enantioselective reaction. In particular, Kita and coworkers have developed the enantioselective spirocyclization reaction of the orfho-substituted phenolic substrates 275 using chiral aryliodine(III) diacetate 276 having a rigid spirobiindane backbone (Scheme 3.115) [346]. Similar enantioselective oxidative spirocyclization reactions of the ort/io-substituted phenolic substrates under catalytic conditions in the presence of chiral iodoarenes or chiral quaternary ammonium iodide catalysts are discussed in Sections 4.1.6 and 4.4. 

The oxidative dearomatization of appropriately substituted phenolic substrates resulting in intramolecular cyclization with the formation of spirocyclic products represents one of the most powerful synthetic tools in modern organic synthesis (Seetion 3.1.11). Kita and coworkers were the first to report a catalytic variant of the oxidative spirocyclization reaction based on the in situ regeneration of a [bis(trifluoroacetoxy)iodo]arene from iodoarene using mCPBA as a terminal oxidant [2]. In a representative example, the oxidation of... 

A metal-firee oxidative spirocyclization of hydroxy methylacrylamide with 1,3-dicarbonyl compounds provides a range of spirooxindole 3,4-dihydro-2H-pyrans, in moderate to good yields. This strategy involves the formation of two C-C bonds and one C-O bond in one step (Scheme 7) (130L5254). 

A recent example of this approach has been reported by Yang and coworkers [172] in their synthesis of crassalactone D 338, using m-CPBA as the oxidant (Scheme 83). Mohapatra et al. [173] used the same conditions in their synthesis of pyrenolide D (341a), while Robertson et al. [141] have used a furan oxidative spirocyclization in studies toward the sawaranospirolides (Scheme 84). 

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