Phenanthridines cycloaddition

By suitable substitution the enaminones can often serve as precursors for heterocycles and preparation of indoles, carbazoles, quinolines, acridines and phenaNthridines can be achieved easily. However, this part of enaminone chemistry can lead to surprising and unexpected reactions if the multifunctional properties of the enaminones are ignored, e.g. ring contraction, ring expansion and other rearrangements are observed. In some cases jft-ketoenamines react as the ene-component in cycloaddition. Enaminones are even suitable synthones for building aromatic rings. 

The attacks of heterocyclic A -oxides, e.g. of pyridine, quinoline, isoquinoline, phenanthridine, etc., on activated alkynes (RC CR R = R = COOMe R = Ph, R = COOEt R = Ph, R = CN) pose similar problems . An acyclic intermediate has been postulated but is rarely detected. Some of the possibilities are illustrated in equation (126) . If the open intermediate is formed, then the paths to the ylid and the 2-substituted quinoline in equation (126) seem simple enough, but several possible mechanisms can lead to the 3-substituted products . Other workers regard the reaction of the nitrone (or azomethine oxide) with alkyne as simple cycloadditions - which yield 2,3-dihydro-l,2-oxazoles since these are often unstable, only decomposition products may be found (equation 127). The construction of the indolizine skeleton initiated by a similar process has been reviewed (equation 128). ... 

The stereochemistry of the 1,3-dipolar cycloaddition of the heteroaromatic iV-imines has been investigated in some detail by using the reaction of phenanthridine N-benzoylimine with a series of activated olefins such as JV-methylmaleimide, maleic anhydride, diethyl maleate, methyl acrylate, methyl methacrylate, and methyl trans-crotonate (e.g., Eq. 30).202 The adducts from the former three have the all-cis stereochemistry. These results are rationalized in terms of secondary molecular orbital interactions. With acrylates such stereospecificity is lost, suggesting that this effect is of lesser importance in these cases (see Table II). 

Product Distribution in Cycloaddition Reactions of Phenanthridine N-Benzoylimine with Olefins... 

The photochemical substitution reactions of 2-naphthoxide anion and o-halophenol (X = Br, I) in an aqueous sodium sulfite solution were also reported Photosubstitution of the sulfo group for hydrogen is observed under irradiation of sulfonated derivatives of hydroquinone. Benzo[a]phenanthridine-5-ones (156) (159) were synthesized by photo-induced substitution and cycloaddition of 3-chloroisoquinolin-l-ones... 

Examples of improved chemoselectivity by immobilized diyne on a solid-support [19-21] or of improved reactivity of less reactive alkynes by use of microwave [21-24] were recently described. A wide variety of diynes and monoynes containing functional groups were applied to this reaction in the past decade. Arylboronates [25, 26] and diiodo benzenes [27, 28] [Eq. (12)] were thus obtained and involved in further transformatiOTis. Several types of compounds able to present biological activities could also be synthesized such as benzo-fused lactams and lactones [23, 29] [Eq. (13)], phtalans [19], indanones [20], indanes [21], phenanthridines [22], benzoproline and tetrahydroisoquinoline derivatives [30, 31], C-arylglycosides and C-arylribosides [32-35]. Recently, this ruthenium-catalyzed [2+2+2] cycloaddition between a diyne and a monoalkyne was also used as reaction step in total syntheses [20, 23, 24, 36]. 

By inventing an intramolecular imino-Diels-Alder cycloaddition of a diene formed by the thermolysis of an oxime-ether, the construction of the alkaloid skeleton, and the usefulness of this methodology, was successfully exemplified, first by the total synthesis of the benzo[c]phenanthridine alkaloid, chelidonine, and then in a beautiful total synthesis of lysergic acid (1). 

The synthesis of haemanthamine illustrates another approach to the ethano-phenanthridine nucleus and is based on the cycloaddition reaction of butadienes and A -pyrroline-4,5-diones to give tetrahydroisatins. Transformation of the key intermediate diol (B) to the desired nucleus has been achieved via an unusual Bischler-Napieralski reaction involving the bridge-head nitrogen. ... 

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