Scheme 7 Synthesis of a-pyrone: tandem 4n-6n electrocyclic concerted process with a C = O function [78]

The C = N version was realized by using azaheteroaryl substituents at the 4-position [79]. The required cyclobutenones 43 were prepared by the addition of the corresponding 2-lithioheteroaromatics (or Pd-catalyzed cross-coupling with 2-stannylheteroaromatics). The usual ring opening followed by intramolecular cyclization of the C = N bond of azaheteroaromatics onto the vinylketene end occurred faithfully to give quinolizin-4-ones 45a, imidazo[1,2-a]pyridin-5-ones 45b, and thiazolo[3,2-a]pyridin-5-ones 45c (Scheme 8).

O R4

Scheme 8 Synthesis of fused pyridones: tandem 4n-6n electrocyclic concerted process with C = N functions [79]

Furan and thiophene have also been utilized in this type of transformation as building blocks. In the same manner, prerequisite structures prepared by cross-coupling as well as traditional carbanion addition were converted ex-pectedly into benzo- and dibenzofurans and their thiophene analogs (i.e., 47 ^ 48) [80]. Likewise, sesquiterpene furanoquinone 51 was synthesized [81], and the total synthesis of the indolizidine alkaloid, septicine 54, was performed with the key step 52 ^ 53 for the pyrrole case [82] (Scheme 9).

Dihydropyridine is another building block. Construction of the pyri-doacridone ring system, which is found in marine alkaloids and often exhibits an array of biological activities (e.g., amphimedine), was accessible from condensation of 5 (R = i-Pr) with 1-BOC-2-lithio-1,4-dihydropyridine 55 (note: the N atom has no nucleophilicity toward the ketene group that is formed transiently upon thermolysis). Neat thermolysis of the 1,2-adduct 56 produced an oxazolone-fused dihydroquinoline 57 as a result of the expected tandem 4n-6n electrocyclizations. The subsequent removal of the protecting pyrrole group and oxidative aromatization, with loss of the oxazolone ring, afforded the aimed-at heteropolycycle 58 [83] (Scheme 10).

The xanthone core is present in a large family of natural products with broad biological activities. Highly substituted xanthone systems with linear and angular fusion were designed along the cyclobutenedione route [84,85]. First, the requisite benzopyrone-fused cyclobutenedione structure (such as 61) was constructed by addition of dithiane anion 59b of salicylaldehyde 59a to dimethyl squarate 5, followed by acid-catalyzed cyclization with elimination of methanol. The next step of adding unsaturated organolithium (61 ^ 62)



52 Ar=3,4-dimethoxyphenyl

54 (septlclne)

Scheme 9 Tandem 4n-6n electrocyclic concerted process with furan, thiophene, and pyrrole rings [80-82]

Scheme 9 Tandem 4n-6n electrocyclic concerted process with furan, thiophene, and pyrrole rings [80-82]

Scheme 10 Tandem 4n-6n electrocyclic concerted process with a dihydropyridine ring [83]

occurred selectively at the carbonyl group opposite the bulky dithiane moiety. The key ring opening step (62 ^ 63) proceeded even at room temperature (practically reflux was applied in THF) to give the target molecule after depro-tection. Another method for obtaining angularly fused xanthones was done by successive treatment of 3-anisoylcyclobutene-1,2-dione with heteroaryl-lithium and methyl triflate and prolonged heating of the adduct (mesitylene, reflux). In a related work using 3-benzoylcyclobutene-1,2-dione, the adduct 64 having a p-dimethylaminophenyl group at the 4-position underwent unusual rearrangement to a furan derivative 66 due to participation of an allenylketene iminium ion intermediate 65 [86] (Scheme 11).

MeOv .0

MeOv .0

0 0

Post a comment