Um sistema catalítico composto por Pd(OAc) 2 e P(o-tol) 3 foi aplicado na reação de Heck entre brometos de arila e diariletenos. Utilizando-se K 2 CO 3 como base e DMF como solvente, olefinas triarilsubstituídas foram obtidas com rendimentos de bons a excelentes. Brometos de arila com substituintes eletroretiradores foram menos ativos para a reação de acoplamento Heck e levaram à formação de produto de homoacoplamento em quantidades substanciais, indicando que a adição oxidativa não deve ser a etapa lenta da reação. A presença de substituintes no diarileteno afetou drasticamente a seletividade da reação. Realizou-se também a dupla arilação do estireno, levando diretamente à olefina triarilsubstituída, com rendimento de 73%.A catalytic system composed of Pd(OAc) 2 and P(o-tol) 3 was found to be effective for the Heck reaction of aryl bromides with diarylethylenes. Using K 2 CO 3 as a base and DMF as a solvent, trisubstituted olefins were obtained in good to excellent yields. Aryl bromides containing an electron-withdrawing group in para position were less reactive for the Heck coupling reaction and gave substantial amount of homocoupling by-product suggesting that oxidative addition is not the rate-determining step. Electron withdrawing group substituent in the para position of stilbene affects the regioselectivity of the reaction. In this case, the phenyl group from the Ph-Pd complex migrates preferentially to the same carbon of the double bond to which the phenyl is bonded. Finally, a one pot sequential double Heck arylation of styrene was performed, giving trisubstituted olefin with an overall yield of 73%.Keywords: Heck reaction, palladium, trisubstituted olefins, double arylation IntroductionPalladium-catalyzed Heck cross-coupling reactions are one of the most efficient methods for the construction of C−C bonds and have found widespread use in organic synthesis.1 Most Heck reactions involves arylation of monosubstituted alkenes (especially acrylates and styrene derivatives) to allow synthesis of disubstituted olefins with regio and stereoselective control. In contrast, fewer studies have been conducted on the arylation of disubstituted olefins or double arylation of mono-substituted olefins, to yield trisubstituted products. Stereocontrol during the synthesis of highly substituted double bonds is a significant challenge in organic synthesis, 2 and the Heck reaction remains an important alternative. In this context, some examples of regio and stereoselective syntheses of trisubstituted α,β-unsaturated compounds, such as nitriles, 3,4 cinnamates 5-10 and aldehydes, 11 through either monoarylation of disubstituted olefins or direct diarylation of monosubstituted olefins, have been reported. Arylation of disubstituted alkenes without an electron-withdrawing group conjugated to the C=C double bond (e.g., α-or β-methylstyrene, 10,12 1,1-diphenylethene and transstilbene)13-15 has also been investigated. However, to the best of our knowledge, no example using substituted stilbenes has been described. Recently, we re...

Graphene framework obtained with a simple methodology as a high efficient sorbent in SPE cartridges for extraction of triclosan.

Z)-Tamoxifen was synthesized from a simple olefin (trans-stilbene) in 5 steps and 40% overall yield (Z/E = 74:26). The phenyl substituted group (4-Me 2 NCH 2 CH 2 OC 6 H 4 ) was attached by a bromination-dehydrobromination-Suzuki reaction sequence. Subsequently, the ethyl group was attached to the triarylated olefin by a bromination-Negishi reaction sequence. Both the Suzuki and Negishi cross-coupling processes are stereospecific, and the stereoselectivity depends only on the bromination-dehydrobromination reactions. (Z)-Tamoxifen was also obtained from trans-stilbene in only 3 steps by using Heck reaction-bromination-Negishi reaction sequence in 57% overall yield (Z/E =65:35).The construction of tetrasubstituted olefins with a high degree of stereocontrol remains a significant challenge in organic synthesis. 1 One example of important tetrasubstituted olefin is (Z)-tamoxifen, which is a selective estrogen receptor modulator (SERM) used in the treatment of breast cancer. 2,3 It is important to mention that the antiestrogenic activity of tamoxifen is highly dependent on the olefin geometry, and several syntheses of tamoxifen and its derivatives have been reported. The basic approach for the synthesis of tamoxifen and derivatives is the coupling of functionalized ketones by lowvalent titanium (McMurry reaction), which, unfortunately, results in a mixture of the desired hetero-ketone coupling and the undesired homo-ketone coupling. 4 Multistep synthesis, involving dehydration 5 and double-bond migration 6,7 reactions, has been used to produce tamoxifen (Z/E = ~1:1). Palladium-catalyzed reactions are versatile methods for carbon-carbon bond formation, and most of the selective syntheses of (Z)-tamoxifen have at least one step involving a Pd-catalyzed cross-coupling reaction. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] One powerful strategy used to obtain tetrasubstituted olefin selectively is to create a substituted vinylic metal substrate by a selective carbometalation of disubstituted alkynes, followed by quenching with an electrophile (iodine or bromine), and then a Pd-cross-coupling reaction or a direct cross-coupling reaction of the vinylic metal substrate. 8-14 On the other hand, Pd-catalyzed threecomponent coupling of aryl iodides, internal alkynes, and arylboronic acids provides a one-step, selective route to tetrasubstituted olefins including tamoxifen. 15 Disubstituted alkynes are also starting materials for the synthesis of tamoxifen, using a Ni-catalyzed arylative carboxylation. 23 We have recently reported that tri-and tetrasubstituted olefins can be obtained in high yields and regioselectivities, using stilbene as the starting material and a Pd-catalyzed cross-coupling process. 24,25 trans-Stilbene is cheaper than alkynes and can be obtained by a Heck cross-coupling reaction of halobenzene and styrene. Therefore, we wish to report here the application of this approach for the synthesis of (Z)-tamoxifen (Scheme 1). The substituted phenyl group (R 1 =4-Me 2 NCH 2 CH 2 OC 6 H 4 ) can be atta...