Indoles polycyclic

The classic addition of C3 tethered amine derivatives onto C2 of indolium ions has been used to access hexahydropyrrolo[2,3-fc]indole frameworks <060L4303, 060F6011>. An alternative and unique strategy for accessing similar pyrrolo[2,3-fc]indole polycyclics 137 has... 

Hiickel 4n -r 2 rule and, 523-524 imidazole and, 529 Indole and. 533 ions and,525-527 isoquinoline and, 533 naphthalene and, 532 polycyclic aromatic compounds and,531-532 purine and, 533... 

Indole-2,3-quinodimethanes [44] 44 are bicyclic outer-ring dienes that are widely used to prepare a variety of heterocyclic polycyclic compounds. These dienes, generated by extrusion of CO2 from lactones, are then trapped by dienophiles. Some examples of Diels Alder reactions of the dienes 44 are reported in Scheme 2.19. 

Polycyclic aromatic hydrocarbons, indole and quinoline derivatives, naphthylamines, azulenes Silica gel G Formation of oxidation products via the initially formed iodine complexes [15]... 

Scheme 1.39. Synthesis of an indole derivative by a three fold cationic polycyclization.

Two new polycyclic pyridoacridine alkaloids, arnoamine B, 289, and its demethylated analogue, arnoamine A, have been isolated from the ascidian Cystodytes sp. These new compounds are the first known examples of pyrroles fused to pyridoacridines, have antifungal properties, and are cytotoxic in several human tumor cell lines <1998JOC1657>. Both these compounds have been synthesized, starting from the hydrazone 290 with a Fischer indole synthesis (Scheme 73) <2000JOC5476>. 

Diels-Alder reaction of the 1,3,4-oxadiazole with the pendant olefin and loss of N2, the C2-C3 7t bond participates in a subsequent 1,3-dipolar cycloaddition with the carbonyl ylide to generate complex polycycles such as 45 as single diastereomers with up to six new stereocenters. That the cascade reaction is initiated by a Diels-Alder reaction with the alkene rather than with the indole is supported by the lack of reaction even under forcing conditions with substrate 46, in which a Diels-Alder reaction with the indole C2-C3 n bond would be required [26a]. 

Wattenberg LW and Loub WD. 1978. Inhibition of polycyclic aromatic hydrocarbon-induced neoplasia by naturally occurring indoles. Cancer Res 38 1410-1413. 

Iwasawa and co-workers developed a facile method for the construction of polycyclic indole derivatives 190a and 190b by the tungsten(0)-catalyzed reaction of A-(2-(l-alkynyl)phenyl)imine 188 with the electron-rich alkenes 189a and 189b (Scheme 32).42b Photoirradiation of a mixture of imine 188 and ketene silyl acetal 189a with 10mol% of... 

Whereas Hegedus [335] and Danishefsky [336] were the first to discover a tandem Heck reaction from o-allyl-A -acryloylanilines leading to tricyclic pyrrolo[l,2-a]indoles or pyridino[l,2-a]indoles [336], it has been the fantastic work of Grigg to unleash the enormous potential of this chemistry. Grigg and his co-workers parlayed their Pd-catalyzed tandem polycyclization-anion capture sequence into a treasure trove of syntheses starting with IV-allyl-o-haloanilines [337-345], Diels-Alder and olefin metathesis reactions can be interwoven into the sequence or can serve as the culmination step, as can a wide variety of nucleophiles. An example of the transformation of 289 to 290 is shown below in which indole is the terminating nucleophile [340],... 

Moreover, polycyclic indole alkaloid-type molecules 225 with a ketopiperazine were prepared by Wang et al. using Ugi-Pictet-Spengler process [68]. Ketocar-boxylic acids 227 were used as bifunctional substrates in Ugi reaction to yield lactams of varying ring sizes (Scheme 41). A diastereomer of hexacyclic indole derivative was crystallized and yielded X-ray diffraction suitable crystal to assign the stereochemistry. 

Scheme 41 Synthesis of polycyclic indole alkaloid-type compounds 225. The X-ray structure of compound 225D is shown in blue sticks (CCDC-749252)...

Wang W, Herdtweck E, Domling A (2010) Polycyclic indole aUcalold-type compounds by MCR. Chem Commun 46(5) 770-772... 

Blechert et al. have proposed a new effective approach to the synthesis of different indole alkaloids using cation domino reactions (95S592, 97AGE1474). The total yield of uleine (7a), produced on the basis of this concept, is 32%, which is quite unique in the synthesis of polycyclic indole alkaloids. Note that this is the total yield, starting from cyclohexenone 46 the yield of the key step of the synthesis - the cyclization of carbazole 47 into 7a is 95% (Scheme 12). 

Since the publication of CHEC-II(1996) <1996CHEC-II(6)1>, in which thermally induced [4+2] cycloadditions have been reviewed, significant progress has been realized in this strategy, especially for the synthesis of polycyclic heterocycles. Cyclophanes 12 containing pyridazine and indole units were used for the synthesis of pentacyclic compounds 13 via a thermally induced transannular inverse-electron-demand Diels-Alder reaction (Equation 2) <20020L127, 2002AGE3261>. 

Similarly, mono- and bicyclic 1,2-diazines tethered to indole dienophiles by only one alkylene chain 14 afford tetra-and pentacyclic condensed carbazoles 15. Unactivated pyridazines undergo these thermally induced [4+2] cycloaddition reactions only very sluggishly. However, the examples with the more activated electron-deficient pyridazines, especially pyridazine diesters and pyridazino[4,5-, pyridazindiones, demonstrate the synthetic usefulness of this strategy for the construction of polycyclic carbazoles (Equation 3) <2004T6495>. 

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