Cai Yudong, Roberts Brian P, Tocher Derek A, Barnett Sarah A
Christopher Ingold Laboratories, Department of Chemistry, University College London, 20 Gordon Street, London, UKWC1H 0AJ.
Org Biomol Chem. 2004 Sep 7;2(17):2517-29. doi: 10.1039/B407215B. Epub 2004 Aug 10.
Alpha-tert-butoxystyrene [H2C=C(OBut)Ph] reacts with alpha-bromocarbonyl or alpha-bromosulfonyl compounds [R1R2C(Br)EWG; EWG =-C(O)X or -S(O2)X] to bring about replacement of the bromine atom by the phenacyl group and give R1R2C(EWG)CH2C(O)Ph. These reactions take place in refluxing benzene or cyclohexane with dilauroyl peroxide or azobis(isobutyronitrile) as initiator and proceed by a radical-chain mechanism that involves addition of the relatively electrophilic radical R1R2(EWG)C* to the styrene. This is followed by beta-scission of the derived alpha-tert-butoxybenzylic adduct radical to give But*, which then abstracts bromine from the organic halide to complete the chain. Alpha-1-adamantoxystyrene reacts similarly with R1R2C(Br)EWG, at higher temperature in refluxing octane using di-tert-amyl peroxide as initiator, and gives phenacylation products in generally higher yields than are obtained using alpha-tert-butoxystyrene. Simple iodoalkanes, which afford relatively nucleophilic alkyl radicals, can also be successfully phenacylated using alpha-1-adamantoxystyrene. O-Alkyl O-(tert-butyldimethylsilyl) ketene acetals H2C=C(OR)OTBS, in which R is a secondary or tertiary alkyl group, react in an analogous fashion with organic halides of the type R1R2C(Br)EWG to give the carboxymethylation products R1R2C(EWG)CH2CO2Me, after conversion of the first-formed silyl ester to the corresponding methyl ester. The silyl ketene acetals also undergo radical-chain reactions with electron-poor alkenes to bring about alkylation-carboxymethylation of the latter. For example, phenyl vinyl sulfone reacts with H2C=C(OBut)OTBS to afford ButCH2CH(SO2Ph)CH2CO2Me via an initial silyl ester. In a more complex chain reaction, involving rapid ring opening of the cyclopropyldimethylcarbinyl radical, the ketene acetal H2C=C(OCMe2C3H5-cyclo)OTBS reacts with two molecules of N-methyl- or N-phenyl-maleimide to bring about [3 + 2] annulation of one molecule of the maleimide, and then to link the bicyclic moiety thus formed to the second molecule of the maleimide via an alkylation-carboxymethylation reaction.
α-叔丁氧基苯乙烯[H2C = C(OBut)Ph]与α-溴代羰基或α-溴代磺酰基化合物[R1R2C(Br)EWG；EWG = -C(O)X或-S(O2)X]反应，使溴原子被苯甲酰基取代，生成R1R2C(EWG)CH2C(O)Ph。这些反应在回流的苯或环己烷中进行，以二月桂酰过氧化物或偶氮二异丁腈为引发剂，通过自由基链机理进行，该机理涉及相对亲电的自由基R1R2(EWG)C加成到苯乙烯上。随后，衍生的α-叔丁氧基苄基加合物自由基发生β-断裂生成But，然后But*从有机卤化物中夺取溴以完成链反应。α-1-金刚烷氧基苯乙烯与R1R2C(Br)EWG类似地反应，在较高温度下于回流的辛烷中使用二叔戊基过氧化物作为引发剂，得到的苯甲酰化产物产率通常比使用α-叔丁氧基苯乙烯时更高。能提供相对亲核的烷基自由基的简单碘代烷烃，使用α-1-金刚烷氧基苯乙烯也能成功地进行苯甲酰化反应。O-烷基O-(叔丁基二甲基甲硅烷基)烯酮缩醛H2C = C(OR)OTBS，其中R为仲烷基或叔烷基，与R1R2C(Br)EWG类型的有机卤化物以类似方式反应，在将最初形成的甲硅烷基酯转化为相应的甲酯后，得到羧甲基化产物R1R2C(EWG)CH2CO2Me。甲硅烷基烯酮缩醛也与缺电子烯烃发生自由基链反应，使后者发生烷基化-羧甲基化反应。例如，苯乙烯基砜与H2C = C(OBut)OTBS反应，通过最初的甲硅烷基酯生成ButCH2CH(SO2Ph)CH2CO2Me。在一个更复杂的链反应中，涉及环丙基二甲基碳自由基的快速开环，烯酮缩醛H2C = C(OCMe2C3H₅-环)OTBS与两分子的N-甲基或N-苯基马来酰亚胺反应，使一分子马来酰亚胺发生[3 + 2]环化，然后通过烷基化-羧甲基化反应将由此形成的双环部分连接到第二分子马来酰亚胺上。
