Jeganmohan Masilamani, Shanmugasundaram Muthian, Cheng Chien-Hong
Department of Chemistry, Tsing Hua University, Hsinchu, Taiwan 30043, Republic of China.
J Org Chem. 2004 Jun 11;69(12):4053-62. doi: 10.1021/jo0496998.
An efficient method for the synthesis of 1,7-enyne derivatives via phosphine-palladium-catalyzed three-component assembling of activated olefins, allylic chlorides, and allenylstannanes is described. Substituted arylethylidene malononitriles 1a-g (RCH=C(CN)(2): R = C(6)H(5) (1a), p-ClC(6)H(4) (1b), p-OMeC(6)H(4) (1c), p-NO(2)C(6)H(4) (1d), 1-naphthyl (1e), 2-furyl (1f), and 2-thienyl (1g)) undergo propargylallylation with allylic chlorides 2a-e (allyl chloride (2a), methallyl chloride (2b), 4-chloropent-2-ene (2c), cinnamyl chloride (2d), and 3-chlorocyclohexene (2e)) and n-tributylallenylstannane (n-Bu(3)SnCH=C=CH(2), 3a) in the presence of Pd(PPh(3))(4) in toluene to afford the corresponding 1,7-enyne derivatives 4a-m in good to excellent yields. The catalytic reaction is highly regioselective, with the propargyl group adding to the carbon where the R group is attached and the allyl group adding to the carbon connected to the CN groups of activated olefins 1a-g. The present catalytic reaction is successfully extended to substituted arylethylidene-1,3-indanediones 5a-j (RCH = (1,3-indanedione): R = C(6)H(5) (5a), p-ClC(6)H(4) (5b), p-BrC(6)H(4) (5c), p-OMeC(6)H(4) (5d), p-NO(2)C(6)H(4) (5e), p-CNC(6)H(4) (5f), p-biphenyl (5g), 1-naphthyl (5h), 2-thienyl (5i), and 2-benzo[b]furane-2-yl (5j)) and substituted 2,2-dimethyl-5-(arylethylidene)-1,3-dioxane-4,6-diones 7a,b (RCH = (1,3-dioxane-4,6-dione): R = p-NO(2)C(6)H(4) (7a), p-OMeC(6)H(4) (7b)). The three-component assembling of these substrates with allylic chlorides (2a,b,d,e) and n-tributylallenylstannane (n-Bu(3)SnCH=C=CH(2), 3a) proceeds smoothly to afford the corresponding 1,7-enyne derivatives 6a-m and 8a-d in good to excellent yields. The catalytic propargylallylation can be further applied to the activated dienes, C(6)H(5)CH=CH=CR(2) (R(2) = (CN)(2) (9a), 1,3-indanedione (9b), 2,2-dimethyl-1,3-dioxane-4,6-dione (9c)), with allylic chlorides (2a,b,d) and allenylstannane 3a to give regio- and chemoselective 1,2-addition products 10a-h in good to excellent yields. A plausible mechanism based on an eta(1)-allenyl eta(3)-allyl palladium intermediate is proposed to account for the catalytic three-component reaction.
描述了一种通过膦 - 钯催化的活性烯烃、烯丙基氯和烯丙基锡烷的三组分组装合成1,7 - 烯炔衍生物的有效方法。取代的芳基亚乙基丙二腈1a - g（RCH = C(CN)₂：R = C₆H₅ (1a)，p - ClC₆H₄ (1b)，p - OMeC₆H₄ (1c)，p - NO₂C₆H₄ (1d)，1 - 萘基 (1e)，2 - 呋喃基 (1f)，和2 - 噻吩基 (1g)）在甲苯中，于Pd(PPh₃)₄存在下，与烯丙基氯2a - e（烯丙基氯 (2a)，甲基烯丙基氯 (2b)，4 - 氯 - 2 - 戊烯 (2c)，肉桂基氯 (2d)，和3 - 氯环己烯 (2e)）以及三正丁基烯丙基锡烷（n - Bu₃SnCH = C = CH₂，3a）发生炔丙基烯丙基化反应，以良好至优异的产率得到相应的1,7 - 烯炔衍生物4a - m。催化反应具有高度区域选择性，炔丙基加到R基团所连接的碳上，烯丙基加到与活性烯烃1a - g的CN基团相连的碳上。目前的催化反应成功扩展到取代的芳基亚乙基 - 1,3 - 茚满二酮5a - j（RCH = (1,3 - 茚满二酮)：R = C₆H₅ (5a)，p - ClC₆H₄ (5b)，p - BrC₆H₄ (5c)，p - OMeC₆H₄ (5d)，p - NO₂C₆H₄ (5e)，p - CNC₆H₄ (5f)，p - 联苯基 (5g)，1 - 萘基 (5h)，2 - 噻吩基 (5i)，和2 - 苯并[b]呋喃 - 2 - 基 (5j)）以及取代的2,2 - 二甲基 - 5 - (芳基亚乙基) - 1,3 - 二氧六环 - 4,6 - 二酮7a,b（RCH = (1,3 - 二氧六环 - 4,6 - 二酮)：R = p - NO₂C₆H₄ (7a)，p - OMeC₆H₄ (7b)）。这些底物与烯丙基氯 (2a,b,d,e) 和三正丁基烯丙基锡烷（n - Bu₃SnCH = C = CH₂，3a）的三组分组装反应顺利进行，以良好至优异的产率得到相应的1,7 - 烯炔衍生物6a - m和8a - d。催化炔丙基烯丙基化反应还可进一步应用于活性二烯C₆H₅CH = CH = CR₂（R₂ = (CN)₂ (9a)，1,3 - 茚满二酮 (9b)，2,2 - 二甲基 - 1,3 - 二氧六环 - 4,6 - 二酮 (9c)），与烯丙基氯 (2a,b,d) 和烯丙基锡烷3a反应，以良好至优异的产率得到区域和化学选择性的1,2 - 加成产物10a - h。提出了一种基于η¹ - 烯丙基η³ - 烯丙基钯中间体的合理机理来解释催化三组分反应。
