Arenes cyclization

In conjunction with work in natural products synthesis, the controlled installation of stereocenters alpha to indole C2 remains of significant interest. In their approach to Clausena alkaloids, e.g., (-)-(5R, 6S)-balasubramide, Wang and co-workers employed an intramolecular 8-CMc/o-epoxide-arene cyclization for installation of a C2-C3 8-membered lactam moiety with excellent enantioselectivity <07OL1387>. The Chen group has reported a diastereoselective reaction between 2-lithioindoles and chiral A -terf-but ane sulfinyl... 

Epoxy-arene cyclizations have been studied extensively by Taylor et al. <87JOC425>. The reaction to give six-membered rings can be specific (Scheme 10). The yields for (3) and (4) are lower than for (2), and this is in accord with the Baldwin rules the former reaction is exo, whereas the latter reactions are endo. 

For years, iminium ion-arene cyclizations have punctuated the construction of members of many classes of indole alkaloids. Cyclizations in these more complex cases often proceed with excellent effi-... 

Westling M, Smith R, Livinghouse T (1986) A Convergent Approach to Heterocycle Synthesis via Silver Ion Mediated a-Keto Imidoyl Halide-Arene Cyclizations. An Application to the Synthesis of the Eiythtinane Skeleton. J Org Chem 51 1159... 

Another direct arene cyclization involves the synthesis of benzimidazoles 17 from A-aryl amidines 16 (Scheme 4) [10]. The cyclization proceeds readily with... 

There are reports of an increasing number of palladium-assisted reactions, in some of which the palladium has a catalytic function. Thus furan and thiophene undergo facile palladium-assisted alkenylation giving 2-substituted products. Benzo[6 Jfuran and TV- acetyl-indole yield cyclization products, dibenzofurans and carbazoles respectively, in addition to alkenylated products (8UOC851). The arylation of pyrroles can be effected by treatment with palladium acetate and an arene (Scheme 86) (81CC254). 

In some instances the attack of the arene on the nitrilium salt occurs at the ipso carbon rather than the ortho carbon. For example, the Bischler-Napieralski cyclization of phenethyl amide 10 affords a 2 1 mixture of regioisomeric products 11 and 12. The formation of 12 presumably results from attack of the ipso aromatic carbon on the nitrilium salt 13 followed by rearrangement of the spirocyclic carbocation 14 to afford 15, which upon loss of a proton vields product 12. ... 

Utilization of a similar [Sc(OTf)3-promoted)] approach by Overman on the ger-anylgeraniol-derived cyclization substrate 98 provided the desired tetracyclization product 99, in which the terminator of the cationic cyclization is an arene group. Compound 99 is then transformed into the kinesin motor protein inhibitor adocia-sulfate 1 (Scheme 8.27) [47]. 

Note. Like acylation, alkylidenation is often carried out with a view to subsequent cyclization. Such alkylidenation is almost invariably done with an arene- or heteroarenecarbaldehyde, a related ketone, or occasionally an ethynylarene appropriate procedures are exemplified here. 

Uemura M (2004) (Arene)Cr(Co)3 Complexes Cyclization,Cycloaddition and Cross Coupling Reactions. 7 129-156 Ujaque G, see Drudis-Sole G (2005) 12 79-107... 

By analogy with the cyclotrimerization of acetylenes into arenes, and with the cocyclooligomerization of nitriles and acetylenes into pyridines (see Scheme 131 in Section V,A,1), the cyclization of benzonitrile into 2,4,6-triphenyl-s-triazine can be achieved by means of Fe(CO)5 or Fe2(CO)9.241... 

An improved synthesis of 3,4-dihydro-2,l-benzothiazine 2,2-dioxide was reported by Togo and co-workers using photochemical conditions . Treatment of A-alkyl 2-(aryl)ethanesulfonamides 18 with (diacetoxyiodo)arenes under irradiation with a tungsten lamp at 20-30 °C afforded 2,1-benzothiazines 19 and 20. Chemical yields and selectivities were dependent upon the choice of solvents and the reactant s substituents 18 (Table 1). When THF and EtOH were used as solvents, the reactions failed to give the cyclized products, since their a-hydrogen was abstracted by the intermediate sulfonamidyl radical. Compound 20 was obtained as a major product when 1,2-dichloroethane was employed as a solvent. In contrast, in the case of EtOAc as solvent, compound 19 was obtained as the major product. 

At present, the chemisty of selenophenes and tellurophenes is a relatively scantily studied area. Nevertheless, a number of new valuable contributions dealing with their chemistry have emerged. Electrophilic cyclization of l-(l-alkynyl)-2-(methylseleno)arenes provides a route to a variety of 2,3-disubstituted benzo[fe]selenophenes, as illustrated by the preparation of the system 88. Other useful electrophiles for similar reactions are E or NBS <06JOC2307>. Similar chemistry has also been employed in preparation of 2,3-disubstituted benzo[f>]selenophenes on solid phase <06JCC163>. In addition, syntheses of 2,3-dihydroselenolo[2,3- >]pyridines have been achieved using radical chemistry <06OBC466>. 

A similar intramolecular alkylation of arene-ene substrates is catalyzed by RuGl3/AgOTf, providing good to excellent yields of cyclization products (chromanes, tetralins, terpenoids, and dihydrocoumarins).25 This method is applied to the synthesis of tricyclic terpenoids, which are formed in nearly quantitative yields with high stereoselectivities (trans cis various between 99 1 and 99 2), as shown in Equation (24). 

Cyclization process of arene-yne substrates has been reported with platinum(rv) catalyst (PtCL ), resulting in C-H activation and functionalization.142 This hydroarylation gives 6-< r/o-products in high yields with good tolerance to different functional groups like amine, ester, and ether. This method provides a rapid access to interesting molecules such as coumarins, chromenes, or dihydroquinolines. 

As expected, reaction of A-aroylpyrroles 28 in the absence of added arene affords the bipyrroles 29 or cyclized product 30 [32, 33], Bipyrrole 31 was prepared via this oxidative coupling reaction [32],... 

Janetka and Rich (78) have utilized the considerable stability of ruthenium-77-arene systems in the synthesis of cyclic tripeptides as analogs of the protease inhibitor K-13 (cf. 34, Scheme 28). Their approach involves the construction of linear tripeptide complexes (35) using diimide/HOBt coupling of [Ru(Cp)(Boc-p-Cl-PheOH)]PF6 (Cp = 775-C5H5) with the appropriate dipeptide ester. Cyclization of 35 affords the biphenyl ether 36, which on photolysis (350 nm) gives 34. 

Among the many useful electrophiles, carbonyl compounds and their derivatives lead to products of the highest value for synthetic endeavors. First experiments with aldehydes and ketones were performed by Hoff, Brandsma and Arens (Scheme 8.15) [12b]. The primary allenyl adducts 60, which are isolable in moderate to excellent yields [12b, 47], serve as starting materials for subsequent cyclizations (see Section 8.2.2.2). 

The first cyclization of a-hydroxyalkoxyallenes goes back to the pioneering experiments of Brandsma, Hoff and Arens, who found that dihydrofuran derivatives 102 are formed by treatment of 101 with KOtBu in DMSO (Scheme 8.26) [12c], This reaction protocol was successfully applied by others [61, 63, 64, 80-83], for example in the preparation of spiro compound 104 (Eq. 8.19) [83] and in the cyclization of 64 leading to a-amino acid-derived dihydrofurans 105 (Scheme 8.27) [61, 63], Acidic hydrolysis of dihydrofurans furnished 3(2H)-dihydrofuranones, which could be used again as carbonyl components in the repetitive addition of lithiated methoxyal-lene 42. This concept was employed in syntheses of racemic [82] and enantiomeri-cally pure [64] primary helical spirocycles. 

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