Diastereo- and Enantioselective Intramolecular [2+2] Photocycloaddition Reactions of 3-(ω′-Alkenyl)- and 3-(ω′-Alkenyloxy)-Substituted 5,6-Dihydro-1H-pyridin-2-ones
Diastereo- and Enantioselective Intramolecular [2+2] Photocycloaddition Reactions of 3-(ω′-Alkenyl)- and 3-(ω′-Alkenyloxy)-Substituted 5,6-Dihydro-1H-pyridin-2-ones
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DOI：
10.1002/chem.200902616
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发表时间：
2010-01-01
影响因子：
4.3
通讯作者：
Bach, Thorsten
中科院分区：
文献类型：
--
作者：
Albrecht, Dominik;Vogt, Florian;Bach, Thorsten
3-（ω ′-烯基）-取代的5，6-二氢-1H-吡啶-2-酮2-4通过由3-碘-5，6-二氢-1H-吡啶-2-酮（8）或更优选地由相应的α-（ω ′-烯基）-取代的8-戊内酰胺9-11通过硒化/消除顺序交叉偶联而制备（5,6 -62%总产率），作为光环化加成前体。3-（ω ′-链烯氧基）-取代的5，6-二氢-1H-吡啶-2-酮5和6是由3-重氮哌啶-2-酮（15）通过在3-位的α，α-氯硒化反应，然后用ω-烯醇盐亲核取代氯离子和氧化消除硒氧化物，以43和37%的总产率获得的。在λ = 254 nm处照射后，前体化合物经历了干净的分子内[2+2]光环加成反应。底物2和5，由两个原子链连接，专门提供相应的交叉产物19和20，底物3，5和6，由较长的链连接，得到直链产物21-23。完全区域选择性和非对映选择性的光环化加成反应以63-83%的产率进行。在手性模板（-）-1和（+）-31存在下，在甲苯中于75 ℃下进行照射，使得反应具有对映选择性，选择性在40和85%ee之间变化。截短的模板rac-31作为成熟模板1的去甲类似物，以8个步骤从肯普三酸（24）制备，产率为56%。随后的拆分得到对映体纯的模板（-）-31和（+）-31。将反应结果与用4-取代的5，6-二氢-1H-吡啶-2-酮和喹诺酮获得的结果进行比较。
3-(omega'-Alkeny1)-substituted 5,6-dihydro-1H-pyridin-2-ones 2-4 were prepared as photocycloaddition precursors either by cross-coupling from 3-iodo-5,6-dihydro-1H-pyridin-2-one (8) or more favorably from the corresponding alpha-(omega'-alkeny1)-substituted 8-valerolactams 9-11 by a selenylation/elimination sequence (56-62% overall yield). 3-(omega'-Alkenyloxy)-substituted 5.6-dihydro-1H-pyridin-2-ones 5 and 6 were accessible in 43 and 37% overall yield from 3-diazopiperidin-2-one (15) by an alpha,alpha-chloroselenylation reaction at the 3-position followed by nucleophilic displacement of a chloride ion with an omega-alkenolate and oxidative elimination of selenoxide. Upon irradiation at lambda = 254 nm, the precursor compounds underwent a clean intramolecular [2+2] photocycloaddition reaction. Substrates 2 and 5, tethered by a two-atom chain, exclusively delivered the respective crossed products 19 and 20, and substrates 3, 5, and 6, tethered by longer chains, gave the straight products 21-23. The completely regio- and diastereoselective photocycloaddition reactions proceeded in 63-83% yield. Irradiation in the presence of the chiral templates (-)-1 and (+)-31 at 75 degrees C in toluene rendered the reactions enantioselective with selectivities varying between 40 and 85% ee. Truncated template rac-31 was prepared as a noranalogue of the well-established template 1 in eight steps and 56% yield from the Kemp triacid (24). Subsequent resolution delivered the enantiomerically pure templates (-)-31 and (+)-31. The outcome of the reactions is compared to the results achieved with 4-substituted 5,6-dihydro-1H-pyridin-2-ones and quinolones.