Cyclizations pancratistatin synthesis

Entry 23 was part of a synthesis of the pancratistatin structure. The lactone ring was used to control the stereochemistry at the cyclization center. Noncyclic analogs gave a mixture of stereoisomers at this center. In this reaction, triphenylstannane gave much better yields than tri-n-butylstannane. 

Few applications of cyclizations to form fused ring 8-lactones or tetrahydropyrans are found. Two consecutive bromolactonizations were used to effect stereoselective dihydroxylation of a cyclohexadi-enone system in a total synthesis of erythronolide B (Scheme S).64 Iodolactonization of an NJV-di-ethylbenzamide derivative to form a ds-fused benzolactone was a key step in a recent synthesis of pancratistatin.641 A di-fused tetrahydropyran was produced in good yield by intramolecular oxymercura-tion as shown in equation (17),59 although attempts to cyclize a more highly functionalized system have been reported to fail.65 Formation of a fused ring tetrahydropyran via an anti-Markovnikov 6-endo sel-enoetherification has been reported in cases where steric and stereoelectronic factors disfavor a 5-exo cyclization to a spirocyclic structure.38... 

Despite a considerable amount of recent work on reactions of vinyl silanes with various kinds of imines [48,49], scant attention has been paid to N-sulfonyl imi-nes in this area. A single study of a vinyl silane/N-sulfonyl imine reaction has been published by McIntosh and Weinreb in the context of an approach to the total synthesis of [1, 3]-dioxolophenanthrene structural types of Amaryllida-ceae alkaloids such as narciclasine (137), lycoricidine (138) and pancratistatin (139) [50]. The substrate used in this approach was vinyl silane aldehyde 140, prepared enantiomerically pure in a straightforward manner from L-arabinose (Scheme 26). The N-tosyl imine derived from this aldehyde could be generated in two different ways. The first involved combination of 140 with N-sulfinyl-p-toluenesulfonamide at 80 °C, followed by exposure of the imine to BF3 etherate at 0°C, leading to a single cyclization product 142 in 36% yield. The second procedure was to simply react aldehyde 140 with p-toluenesulfonamide and BF3 etherate (-78°C -rt) to afford a 9.5 1 mixture of 142 144 in -80% yield. It was pro-... 

If a radical is generated in a substrate that also has a it bond in the molecule, intramolecular cyclization can occur (as in 64 65). The highly reactive radical center is positioned to react with the it bond of the alkene, as shown, and the product (65) can be trapped to give the final product. Radical cyclization reactions will be discussed in Section 13.7. A synthetic example is taken from Rigby s synthesis of (+)-pancratistatin, in which photolysis of 66 generated an aryl radical that added to the alkene unit intramolecularly to give a 50% yield of 67. For a brief discussion of this and other pancratistatin syntheses, see Section 10.7. 

Similarly, ohgocycles are obtained from appropriate allyl benzyl ethers as outlined with representative examples in Scheme 21.i i Stereochemical aspects of Pd-catalyzed cyclizations in connection with the synthesis of pancratistatin and related natural products have been studied intensively (second reation in Scheme 21). ... 

Rigby s studies on the synthesis of alkenylisocyanates fostered the preparation of a suitable substituted aryl enamide, which on photocyclization yielded the polysubstituted pentacyclic system. Key to the success of this process is the hydrogen bond between the phenolic OH and the carbonyl group, which restricts the rotation around the aryl-amide bond and directs the cyclization. Further functionalization allowed the total synthesis of pancratistatin (272) and narciclasine (68) (275) (Scheme 11). The [4-1-1] cycloaddition of bis(alkylthio)carbenes with vinyl isocyanates was the key process in a recent synthesis of (+)-mesembrine (92) 274). 

Haseltine has described an enantioselective formal synthesis of pancratistatin in which the stereocontrol is driven by the aeetonide of conduritol A. The enantioselective hydrolysis (desymmetrization) of this compound was achieved with a lipase, and the aryl-cyclohexane ring bond was formed through an intramolecular cyclization of the activated benzene ring with an allylic triflate (278). Plumet reported a total synthesis of (-l-)-7-deoxypaneratistatin based on the conjugate addition of an aryl-lithium species to a bicyclic conjugated sulfone derived from furan, which enabled the efficient installation of the six stereogenic centers of the cyclohexane ring (279) (Scheme 13). 

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