Cycloaddition strong base-induced

An improved total synthesis of the aglycone (180) of 11-deoxyadriamycin-type antibiotics, which show stronger antineoplastic activity and/or less car-diotoxicity than daunomycin and adriamycin, was accomplished by applying the method to dihydroxyacetone (180) from ethynylcarbinol (182), prepared by strong base-induced cycloaddition of the substituted tetrahydrohomophthalic anhydride (181) [137], using PIFA [78] (Scheme 46). 

Thiophene analogs of daunomycin (172, 173) were prepared in multistep reactions. The synthesis is based on a strong base-induced cycloaddition of homophthalic anhydrides. In the final step, glycosidation yielded a mixture of CL- and )S-glycosides from which the a-isomer was separated (87TL3971). 

Homophthalic anhydrides undergo a strong-base induced [4 - - 2] intra- or intermolecular cycloaddition reaction with dienophUes to afford various types of polycyclic peri-hydroxy aromatics in a single step (equation 123). This elegant strategy has been employed in the synthesis of many biologically important compounds such as fredericamycin galtamycinone and dynemycin A. ... 

Syntheses of Anthracyclines and Fredericamycin A via Strong Base-Induced Cycloaddition Reaction of Homophthalic Anhydrides... 

We now present the chemistry of homophthalic anhydrides, mainly addressing the strong base-induced [4 + 2]-cycloaddition reaction with the C - C double bond, especially in quinone and dienophiles, and its application to the syntheses of anthracyclines and fredericamycin A. 

Isobenzofurans have the useful property of undergoing cycloaddition reactions with dienophiles, and this has been exploited in many elegant reaction schemes. Hence, new routes to suitably substituted derivatives are always welcome. It has been known for some time that strong base induced 1,4-elimination of allylic ethers is a general reaction and this reaction has now been applied to the synthesis of isobenzofuran in solution (99) (Scheme 11). Keay et al. have... 

The alkylidenecarbenes generated via base-induced a-elimination can also be trapped by cycloaddition with external alkenes. For example, the treatment of alkenyliodonium salt 55 with a strong base in the presence of excess styrene gives methylenecyclopropane 56 in good yield (Scheme 26) [47]. 

Similarly, Boeckmann et al. report the reaction of azoniaspiro enaminium salts 64 with strong organic bases such as l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to induce ring opening (Equation 16) < 1997T8941 >. This was found to be a convenient route to trienes 65 (Table 4) which were then employed in intramolecular [4+2] cycloaddition reactions. 

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