Nitrogen Heterocycles
2.2. Literature Methods
Metal catalyzed reductive coupling between alkyne and epoxide for C-C bond formation was developed with complete (>95:5) regioselectivity. This methodology unlike 1,n-enyne cyclization requires -system of one molecule (alkyne) and functional group that has no multiple bonds (epoxide). Jamison and his group described a novel methodology for nickel catalyzed multicomponent coupling reactions. This method demonstrated intermolecular and intramolecular reductive coupling of alkynes and epoxides using Bu3P and Et3B as reducing agents. Here, the usually disfavoured endo epoxide-opening product in alkyne-epoxide reductive cyclizations was shown, thus, the compound 8 in presence of Ni-catalyst underwent cyclization to give the compound 9 (Scheme 2.2.1).10
Scheme 2.2.1
Chung et al. reported a methodology which describes Gold(I)-catalyzed cyclization of enynes containing an olefinic cycle. Enynes bearing a cyclic olefin 11 were prepared by a rhodium- catalyzed intermolecular [4 + 2] cycloaddition of diynes 10 with 2,3-dimethylbutadiene in 30 min with high yields in the presence of dichloromethane at room temparature. These compounds then subjected to Diels alder reaction, using gold-catalyst to afford the expected polycyclic diene compound 12 in 85-99% yields. Consecutive rhodium-catalyzed Diels-Alder/gold(I)-catalyzed cycloisomerization reactions were integrated in one-pot. First, Diels-Alder reaction was carried out in the presence of [Rh(NHC)(cod)Cl]/AgSbF6, after completion of the reaction, Au(PPh3)Cl and AgSbF6 were added, and the whole mixture was stirred at the same temperature for 1 h (Scheme 2.2.2).11
Scheme 2.2.2 TH-1580_11612224
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Liu and co-workers reported a one-pot operation for the highly diastereo and enantiospecific synthesis of bicyclic heterocycles with multiple stereogenic centers. Tungsten-promoted two new cycloadditions for common epoxides and functionalized alkynes in the presence of Lewis acid catalyst was shown. Alkynyltungsten complex 13 and propargyltungsten complex 15 in the presence of BF3.Et2O underwent [3+2] and [3+3] cycloaddition in dichloromethane at -40 oC to give enantiospecific bicyclic lactones 14 and 16. (Scheme 2.2.3).12
Scheme 2.2.3
Chatani and his group proposed a methodology for the skeletal reorganization of enynes in the presence of Lewis acid as a catalyst. The reaction of 1,6-enynes with an alkyl group at the acetylenic carbon 17 in the presence of 10 mol % of InCl3 in toluene at 80 oC, resulted in a new type of skeletal reorganization to give 1-allyl-1-cyclopentenes 18 in good yields, in which a terminal olefinic carbon migrates between the acetylenic carbons (Scheme 2.2.4).13
Scheme 2.2.4
Pericas and co-workers developed a one-pot procedure for the synthesis of triazolooxazepinols, triazolodiazepinols and triazolothiazepinols via stereospecific and regioselective epoxide ring opening followed by intramolecular azide-alkyne cycloaddition under metal-free conditions.
Treatment of phenyl glycidyl propargylethers or amines or thioethers 19 with 3 equivalents of NaN3 in t-BuOH/H2O under micro-wave (MW) irradiation condition gave a bicyclic systems TH-1580_11612224
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featuring a triazole ring fused to a seven membered hetrocycles 20. The reaction gave single diastereomer having the trans configuration in a good to moderate yields (Scheme 2.2.5).14
Scheme 2.2.5
Echavarren et al. reported a strategy which describes the formation of oxepane derivatives via oxidative ring opening of 3-oxabicyclo[4.1.0]hept-4-enes 22, formed by the intramolecular Pt(II) catalyzed cyclopropanation of enol ethers by alkynes. The facile oxidative cleavage was performed with DDQ or CAN to give seven-membered ring double acetals 24. In addition, a novel benzannulation had been found to take place by simply heating the cyclopropane derivatives in the presence of a protic acid to provide the compound 23 (Scheme 2.2.6).15
Scheme 2.2.6
Dake and co-workers demonstrated an alternative route for the synthesis of azahydrindan. Cyclic ene-N-p-toluenesulfonamides tethered to an electron-deficient alkyne 25 under the influence of catalytic Pt(II) salts (PtCl2 or [dppbPtµ-OH]2(BF4)2) or AgOTf cyclised to produce 26 in a good to moderate yields, ranging from 47% to 99%. The resulting functionalized 2-azahydrindans can be further manipulated using the Diels−Alder reaction. Thus, the synthetic concept is based on TH-1580_11612224
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tandem cycloisomerization−cycloaddition reactions in one-pot, two-step process which generate highly functionalized 1-azadecalin ring systems in a highly stereocontrolled manner (Scheme 2.2.7).16
Scheme 2.2.7
Yu and co-workers developed a new alternative route for the synthesis of vinylic C-Cl and C-Br bond. Here, FeCl3- and FeBr3-promoted cyclization/halogenation of alkynyl diethyl acetals 27 gave (E)-2-(1-halobenzylidene or alkylidene)-substituted five-membered carbo- and heterocycles 28 selectively.The compound then subjected to Suzuki coupling with aryl boronic acid to afford the coupling product 29. The present protocol has provided a new alternative route to vinylic C- Cl and C-Br bond formation (Scheme 2.2.8).17
Scheme 2.2.8
Evans and his coworkers developed a new method that demonstrates intermolecular metal catalyzed [4 + 2 + 2] cycloaddition. The reaction of heteroatom-tethered enyne 30 and 1,3- butadiene in the presence of the Wilkinson catalyast and a silver salt led to a fused five and eight-membered ring product 31 as well as 32. Depending on the metal counterion, excellent selectivity can be obtained for either the homo- or heterocycloaddition adducts. The stereochemistry of the reaction was also studied by introducing a stereogenic center at C-2 of 33, which leads to a diastereoselective product 34. (Scheme 2.2.9).18
TH-1580_11612224
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40 Scheme 2.2.9
Yamamoto and his group developed a one pot procedure for the synthesis of vinylnaphthalene derivatives 37 via PtBr2-catalyzed consecutive enyne metathesis-aromatization in good to moderate yields. In this reaction Pt-catalyst plays a dual role. 1,7-enynes 35, fused with an aromatic ring and bearing a leaving methoxy group at the 4-position, in the presence of PtBr2
underwent enyne metathesis to produce an intermediate 36 which was isolated. The presence of a methoxy substituent in the tether further extends the scope of this reaction to generate an aromatic ring 37 where PtBr2 acts as a lewis acid to facilitate elimination of MeOH from the isolated intermediate to give the aromatized product (Scheme 2.2.10).19
Scheme 2.2.10