Platinum-catalyzed synthesis of ýý-keto tetrahydropyrans and cyclic dienolethers.
Platinum-catalyzed synthesis of ýý-keto tetrahydropyrans and cyclic dienolethers.
复制标题
铂催化合成α-酮四氢吡喃和环状二烯醚。
DOI：
10.1002/asia.201100113
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
DeBrabander,JefK
中科院分区：
文献类型：
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作者：
Liang,Qiren;Qian,Mingxing;Razzak,Mina;DeBrabander,JefK
自然界为我们提供了似乎无数的含氧环框架，挑战着有机化学家设计出高效、温和且日益通用的制备程序。[1]许多有趣的分子结构已被确定为反复出现的挑战；我们在金属催化的炔烃氢烷氧基化、[2]丙叉取代和丙叉酯的环异构化领域的持续努力[3]引导我们解决了其中的一些挑战。以前，我们证明了类型1的w-羟基丙酸乙酸酯可以经金催化的环异构化反应生成相应的烯醇酸酯2，以及经历铂催化的丙烯酸基取代为类型3的醚(方案1)。[3]前者的转化提供了合成有用的b-酮基四氢吡喃构筑块的入口，例如4，在烯醇酸2的甲醇分解后，从而建立了一个平台，从该平台合成具有1，3-双加氧模式的更复杂的聚酮类天然产物。最近，Jung和Floreancig报道了一种通过金催化的w-羟基丙烯酸醚的环化反应来合成b-酮四氢吡喃的方法。[4，5]虽然这种方法非常有用，但我们推测我们可以直接从炔丙醇(1！4；R=H)中获得这些b-酮四氢吡喃，从而消除了通过醚化或酯化来激活丙叉醇的需要。此外，我们还想研究是否有可能利用位于生殖器中心远侧的系绳(5)内嵌有一个悬挂的亲核体，使生殖器单位参与环化。我们推测这一操作将产生环二烯醚6，这是一种重要的结构基序，用作合成中间体，存在于许多天然产物中，如抗炎鹰嘴豆素[6]和心脏阻滞剂脱水瓜尼醇。[7]在此，我们报告了这些目标的成功执行。在初步筛选可以执行丙炔醇直接环异构化的催化剂时，我们发现Zeise S二聚体[{Cl2PtACHTUNGTRENUNG(CH2CH2)}2]优于其他实验体系，包括金(I)体系。如表1所示，铂(II)催化的丙叉醇环异构化为b-酮基四氢吡喃是在温和的条件下(CH2Cl2，RT，敞开空气)进行的，具有很宽的内炔底物范围。末端炔不能得到所需的b-酮基四氢吡喃(表1，条目1)，如具有空间封闭取代基的底物一样(例如，TMS，TBU；表1，条目3和4)，导致原料的回收和一些分解。然而，芳香族(表1，条目2)、环烷基(表1，条目5)和烷基取代基(表1，条目6-8)以非常好的产率(大于80%)被转化。这种方法的适用范围很容易扩展到制备其他类别的杂环。在系绳中加入额外的氧原子(表1，条目9-12)可获得1，4-二氧六环，而氮夹杂(N±Boc，表1，条目13-15)生成吗啡。这个
Nature has presented us with a seemingly innumerable range of oxygen-containing cyclic frameworks, challenging organic chemists to devise efficient, mild, and increasingly general procedures for their preparation.[1] Many interesting molecular architectures have been identified as recurring challenges; our continued efforts in the areas of metal-catalyzed hydroalkoxylation of alkynes,[2] propargylic substitutions, and cycloisomerization of propargylic esters [3] have led us to address some of these challenges. Previously, we demonstrated that w-hydroxy propargylic acetates of type 1 could undergo a gold-catalyzed cycloisomerization to form the corresponding enolacetates 2, as well as undergoing platinum-catalyzed propargylic substitution to ethers of type 3 (Scheme 1).[3] The former transformation provided entry to synthetically useful b-keto tetrahydropyran building blocks, such as 4, after methanolysis of the enolacetates 2, thereby establishing a platform from which to synthesize more-complex polyketide natural products bearing the 1, 3-dioxygenation pattern. Recently, Jung and Floreancig reported a route to b-keto tetrahydropyrans via a gold-catalyzed cyclization of w-hydroxy propargylic ethers.[4, 5] Whilst this method is very useful, we postulated that we could access these b-keto tetrahydropyrans directly from propargylic alcohols (1! 4; R= H), thereby eliminating the need to activate the propargylic alcohol via etherification or esterification. Furthermore, we also wanted to investigate the possibility of engaging the propargylic unit in a cyclization with a pendant nucleophile embedded within a tether located distal from the propargylic center (5). We postulated that this operation would lead to cyclic dienolethers 6, an important structural motif used as synthetic intermediates and present in a number of natural products, such as the anti-inflammatory falconensins [6] and the heart-blocking agent anhydrocunaniol.[7] Herein, we report the successful execution of these objectives.During an initial screen to discover catalysts that would perform the direct cycloisomerization of propargylic alcohols, we found Zeise s dimer,[{Cl2PtACHTUNGTRENNUNG (CH2CH2)} 2], to be superior to other systems trialed, including gold (I) systems. As shown in Table 1, the platinum (II)-catalyzed cycloisomerization of propargylic alcohols into b-keto tetrahydropyrans occurs under mild conditions (CH2Cl2, RT, open to air), with a broad substrate scope for internal alkynes. Terminal alkynes failed to give the desired b-keto tetrahydropyrans (Table 1, entry 1), as did substrates with sterically encumbering substituents on the alkyne (eg, TMS, tBu; Table 1, entries 3 and 4), resulting in recovery of starting material and some decomposition. However, aromatic (Table 1, entry 2), cycloalkyl (Table 1, entry 5), and alkyl substituents (Table 1, entries6–8) were converted in very good yields (greater than 80%). The scope of this method was easily extended to prepare other classes of heterocycles. The inclusion of additional oxygen atoms into the tether (Table 1, entries 9–12) provided access to 1, 4-dioxanes, whilst nitrogen inclusion (NÀBoc, Table 1, entries 13–15) generated morpholines. The