Alkene-mediated cyclizations

Fused cycbpentenones. An intramolecular alkene-alkyne cyclization mediated by Co2(CO)8 provides a route to bicyclic [3.3.0]enones (equation I).1 This reaction provides... 

The live-ring closure of prostereogenic radicals constructs two new stereogenic centers with good diastereoselectivity, as demonstrated by the trimethyltin hydride mediated cyclization of an ester-substituted diene4. The reaction proceeds via regioselective addition of the stannyl radical to the terminal end of the less substituted alkene and subsequent cyclization. 

For strychnine 3, the ketone 11 was converted to the alkene 12 by reduction of the enol triflate derived from the more stable enolate. Deprotection and acylation gave 13, which was cyclized with Pd to give, after equilibration, the diene 14. Alkylation, to give 15, followed by Pd-mediated cyclization then gave 16, which was reduced and cyclized to (-)-strychnine 3. 

Samarium(II) iodide-mediated cyclization of aryl radicals onto alkene and alkyne acceptors provides an excellent route to nitrogen- and oxygen-based heterocycles (eq 29). ... 

Metal-mediated cyclizations that rely on the initial complexation of an alkene or alkyne around a low oxidation state metal center are often sensitive to the presence of additional substituents (particularly electron-donating substituents), and relatively more stringent reaction conditions are often required for successful cychzation. This effect was noted in the Ni-catalyzed formal [4 -I- 4] cycloaddition reactions developed by Wender and Tebbe and is apparent when one compares the reported facility of Pd-catalyzed linear dimerization of 1,3-butadiene versus that of substituted 1,3-dienes. Similarly, the initial attempts at Pd-catalyzed cyclization of bisdiene 70a (Scheme 22) were rather disappointing. Using 0.05 equiv of [Pd(OAc)2/3 PhjP] (THF, 65 °C, 12 h), only a small... 

For cyclizations via epoxide opening leading to C-glycosides and related compounds, see [2,204-206]. For the synthesis of C-glycosides and related compounds by episelenonium-mediated cyclizations, see [2, 207]. For episulfonium ion promoted cyclizations of hydroxy alkenes, see [2]. For the preparation of C-glycosides... 

PdCl2, 1.1 equiv AgBp4, room temperature, then NaBlLj) to provide 93a. TheiV-methyl derivative 92b also cyclized cleanly, ruling out a mechanism involving iV-palladation followed by rearrangement to a C(2)-palladated species. Indole 94, with one additional carbon in the linker between the indole and the bicyclooctane moiety, cyclized to form both 95 and 96. Oxindole 96 likely arose from palladation-cyclization at C(4), followed by air oxidation. Lastly, indole 97, featuring an exocyclic alkene, underwent the palladium(II)-mediated cyclization to afford compound 98 in good yield. 

Another cobalt-mediated cyclization reaction is the Pauson Khand reaction (PKR). In a [2 -H 2 - - 1] fashion, the reaction of TMSA with alkenes delivers regioselectively silylated cyclopen-tenones. Following the trend typically observed in the PKR, the bulky TMS-group is always positioned a to the carbonyl group (eqs 37 and 38)7 ... 

In the presence of various functional groups in an appropriate distance from the alkenyl or alkynyl moieties, substituted alkenes or alkynes may undergo tandem reactions comprising hydroesterification as one of the individual steps. The bicylic cis-fused lactone core of plakortones, a novel class of activators of cardiac SR-Ca -pumping ATPase, was efficiently accessed by a palladium(II)-mediated cyclization-intramolecular hydroesterification reaction sequence. Cyclization of the starting enediols was carried out using either a small excess of Pd(II) [47] or a catalytic amount of Pd(II) and an excess of Cu(II) as the reoxidant [48],... 

YoshiakiNishibayashi of the University of Tokyo devised (Angew. Chem. Int. Ed. 2009, 48, 2534) Ru catalysts for the cyclization of an enyne such as 21 to the cyclohexadiene 22. Laurel L. Schafer of the University of British Columbia developed (/. Am. Chem. Soc. 2009,131, 2116) a Zr catalyst for the diastereocontro lied cyclization of amino alkenes such as 23. Hongbin Zhai of the Shangahi Institute of Organic Chemistry showed (J. Org. Chem. 2009, 74, 2592) that the Mo-mediated cyclization of 25 also proceeded with high diastereocontrol. Even more impressive was the selectivity Kozo Shishido of the University of Tokushima demonstrated (Tetrahedron Lett. 2009, 50, 1279) for the cyclization of 27. 

The p-lactone cyclization precursors come from Romo and Yang s tandem Mukaiyama aldol lactonization (TMAL) process (Scheme 7) [10]. As an example of this, lactone 25 was the product of the ZnCl2-mediated cyclization of a-benzyloxy aldehyde 24 with thio-ketene acetal 23. Ozonolytic cleavage of the alkene gave 26. 

Allylic carbonates are most reactive. Their carbonylation proceeds under mild conditions, namely at 50 C under 1-20 atm of CO. Facile exchange of CO2 with CO takes place[239]. The carbonylation of 2,7-octadienyl methyl carbonate (379) in MeOH affords the 3,8-nonadienoate 380 as expected, but carbonylation in AcOH produces the cyclized acid 381 and the bicyclic ketones 382 and 383 by the insertion of the internal alkene into Tr-allylpalladium before CO insertion[240] (see Section 2.11). The alkylidenesuccinate 385 is prepared in good yields by the carbonylation of the allylic carbonate 384 obtained by DABCO-mediated addition of aldehydes to acrylate. The E Z ratios are different depending on the substrates[241]. 

Zinc-mediated reductive dimerization cyclization of 1,1-dicyano-alkenes occurs to give functionalized cyclopentenes in good yields under saturated aqueous NH4CI-THF solution at room temperature. The trans isomers are the major products (Eq. 10.38).89... 

The above-mentioned important and impressive applications of titanocene mediated and catalyzed epoxide opening have been achieved by using the already classical 5-exo, 6-exo and 6-endo cyclizations with alkenes or alkynes as radical acceptors. Besides these achievements, the high chemoselectiv-ity of radical generation and slow reduction of the intermediate radicals by Cp2TiCl has resulted in some remarkable novel methodology. 

TMC ATRA reactions can also be conducted intramolecularly when alkyl halide and alkene functionalities are part of the same molecule. Intramolecular TMC ATRA or atom transfer radical cyclization (ATRC) is a very attractive synthetic tool because it enables the synthesis of functionalized ring systems that can be used as starting materials for the preparation of complex organic molecules [10,11], Furthermore, halide functionality in the resulting product can be very beneficial because it can be easily reduced, eliminated, displaced, converted to a Grignard reagent, or if desired serve as a further radical precursor. The use of copper-mediated ATRC in organic synthesis has been reviewed recently and some illustrative examples are shown in Scheme 3 [10,11,31,32,33],... 

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