Ring Expansion Methods

In an extension of known methodology, Conia et al. have shown that ketones can be expanded by one carbon to 2-methylenones [i.e. (228) - (229)] by the addition of chloro(methyl) carbene to the trimethylsilyl enol ether derived from (228), followed by elimination of trimethylsilyl chloride. A somewhat related approach can be used to ring-expand the acyloin condensation products (230) to 1,3-diones (231).  

Seebach, T. Weller, G. Protschuk, A. K. Beck, and M. S. Hoekstra, Helv. Chim. Acta, 1981, 

Nishiguchi, T. Hirashima, T. Shono, and M. Sasaki, Chem. Lett, 1981, 551. 

Improved conditions have been found for the synthesis of cycloalkynones by Eschenmoser fragmentation of bicyclic epoxy-ketones. Various cyclodecene derivatives have been prepared from the Diels-Alder adduct of cyclo-octyne and furan-3,4-dicarboxylates, ° and some simple cyclodecanones have been obtained from 9-decalinols by radical-induced ring cleavage.  

The remarkable zip reaction, previously used for the ring expansion of N aminoalkylated lactams, can also be applied to appropriate carbocyclic systems, e.g. (238) - (239). =  

Two more papers on the synthesis of cyclic allenes have appeared which utilize the alkyl-lithium-induced opening of a fused dihalo-genocy clopropane such as (1 1 6 ). Access to the ophiobolin 

The selenone (122) reacts with enolate anions to form either the 

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Scheme 16.23 Preparation of heterocycles via the ring expansion method.

Kametani and co-workers used a previously demonstrated ring expansion method to construct the isopavine skeleton (144,145). The method was successfully applied to the synthesis of ( )-reframidine (27) (Scheme 23) (145). Treatment of the 3-aryl-3,4-dihydroisoquinolinium iodide 115 with diazomethane furnished aziridinium iodide 116. On standing in 6 N hydrochloric acid, crude 116 underwent a one-step ring expansion-ring closure to afford ( )-reframidine in 20% yield. The same product could be obtained via benzazepine 118 depending on the reaction conditions. It has been postulated that the aziridinium iodide 116 may have formed a transitory quinonoid intermediate 117 which is attacked... 

The overall sequence of cyclopropanation of a cyclic silyl enol ether, chlorination with FeCl3, and dehydrochlorination represents a very reliable one-carbon ring expansion method for cycloalkanomer (Table 11). 

A novel entry to decahydrocyclopentacyclooctene derivatives via the intramolecular photocycloaddition of fused a,/3-unsaturated y-lactones has been developed (80CC1011). Irradiation of the butenolide (153) in acetone solution gave both the fused and bridged photoadducts (154) and (155) (2-3 1). The major adduct was hydrolyzed, oxidized and esterified to afford (156). Reductive cleavage of the unsaturated keto ester (156) with lithium in ammonia afforded a five-component mixture of a,/3- and /3,y-unsaturated esters. Equilibration with 0.1M sodium methoxide in methanol converted the mixture into a single a,j8-unsaturated ester (157 Scheme 34). This annelative two-carbon ring expansion method may find application in the synthesis of ophiobolin and ceroplastol sesterterpenes. 

Thies ° has shown that the 1,3-oxy-Cope rearrangement can be used to advantage as a two-carbon ring expansion method (equation 9). ° Addition of vinyllithium to a cyclic p. -unsaturated ketone (6), followed by pyrolysis of the TMS ether (7) of the resulting alcohol, gives predominandy the 1,3-rearrangement product (8). 

Perhaps the commonest ring expansion method of azocine synthesis is by Beckmann or Beckmann-type rearrangements of cycloheptanone... 

Ring Expansion Methods and Spiro-ring Compounds... 

In an attempt to dehydrate the 6-hydroxy-dithianes (113) using 2 only the ring-expanded products (114) were isolated, and this has been developed into a general ring expansion method which also... 

Scheme 6.9 Oxidative ring expansion method for macrolide synthesis.

A short synthesis of the dihydrothiepin (250) has been derived, using an extension of a novel ring-expansion method that was originally developed for the synthesis of 2,6-di-t-butylthiopyrans. ... 

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