Remote Control of Regio- and Diastereoselectivity in the Hydroformylation of Bishomoallylic Alcohols with Catalytic Amounts of a Reversibly Bound Directing Group
Remote Control of Regio- and Diastereoselectivity in the Hydroformylation of Bishomoallylic Alcohols with Catalytic Amounts of a Reversibly Bound Directing Group
复制标题
DOI：
10.1002/anie.200905949
复制
发表时间：
2010-01-01
影响因子：
16.6
通讯作者：
Breit, Bernhard
中科院分区：
文献类型：
--
作者：
Gruenanger, Christian U.;Breit, Bernhard
烯烃的氢甲酰化反应是均相催化在工业上的最大应用，全世界每年生产约900万吨氧产物。[1,2]在这种转化过程中，烯烃在金属催化剂的存在下与合成气反应，生成相应的醛，这种转化完全符合原子经济性的标准形成的醛是有用的官能团，适合于进一步的骨架扩展转化，甚至可以作为串联过程进行尽管烯烃的氢甲酰化反应有这些明显的优点，但由于难以同时控制区域选择性和立体选择性，因此在复杂的合成过程中仍不常用。目前已有许多催化剂可使末端脂肪族烯烃的氢甲酰化反应选择性地得到线性产物相反，没有一种催化剂能使端烯烃和内烯烃发生一般的氢甲酰化反应，从而选择性地生成支链产物这个问题的一个解决方案是使用可移动的催化导向基团，共价结合到底物上，在烯丙醇和均烯丙醇的反应中促进区域控制和无环立体控制然而，这种方法的一个明显缺点是需要额外的步骤来引入和去除导向基团，并且需要化学计量量。更可取的是使用催化量的导向基团，正如我们最近在一种基于底物和催化剂体系之间互补氢键的超分子方法中所展示的那样另外，我们和其他人已经报道了使用共价但可逆地与底物结合的催化导向基团。[9,10,11]因此，我们确定了二苯基膦酸盐是氢甲酰化条件下醇可逆酯交换反应的理想体系。因此，使用该催化剂体系可以实现高区域选择性的同丙烯醇氢甲酰化反应，并以优异的收率生成g-内酯醇（方案1a）所观察到的高区域选择性的基础是分子内6-外三角氢化的过渡态优于7-内三角氢化的过渡态。在这里，导向基团所结合的官能团与反应官能团的关系为1,3；这是迄今为止报道的在定向氢甲酰化中实现有效底物控制的最大距离我们在此报道，在氢化甲酰化过程中，有可能将引导基团与羟基结合的羟基官能团再远离反应官能团一个原子，变成一个遥远的1,4关系（方案1b），并且仍然获得优异的区域选择性和非对映选择性。这可以在原子经济制备范围广泛的d-内酯和内酯，甚至是聚丙酸天然产物的结构单元，所有这些都是有机合成的重要组成部分。我们开始了对戊-4-烯-1-醇的氢甲酰化的研究(1)，采用了我们之前为同丙烯醇的位置选择性氢甲酰化开发的反应条件（表1）。令我们惊讶的是，一个平稳的氢甲酰化反应被观察到，具有极好的区域选择性，有利于支化产物，邻苯二甲酸酯2（表1，条目1）。然而，反应速度比同丙烯醇慢，因此转化速度也慢
The hydroformylation of olefins is the largest volume application of homogeneous catalysis in industry with about 9 million tons of oxo products produced worldwide each year.[1, 2] In this transformation alkenes are reacted with synthesis gas in the presence of a metal catalyst to furnish the homologated aldehydes—a conversion in complete accord with the criteria of atom economy.[3] The aldehydes formed are useful functional groups suitable for further skeletonexpanding transformations, which may be performed even as tandem processes.[4] Despite these obvious advantages, the hydroformylation of olefins is still not commonly employed in the course of a complex synthesis, because of the difficulty in controlling regio-and stereoselectivity simultaneously. A number of catalysts exist today that allow the hydroformylation of terminal aliphatic alkenes to give linear products selectively (linear-selective).[5] Conversely, no catalyst is known for a general hydroformylation of terminal and internal alkenes to give branched products selectively (branched-selective).[6] One solution to this problem has been the use of removable catalyst-directing groups covalently bound to the substrate that facilitate both regiocontrol and acyclic stereocontrol in reactions of allylic and homoallylic alcohols.[7] However, an obvious drawback of this approach is the requirement of additional steps for introduction and removal of the directing group as well as the need for stoichiometric amounts. More preferable would be the use of catalytic amounts of the directing group, as we have recently shown in a supramolecular approach based on complementary hydrogen bonding between the substrate and the catalyst system.[8] Alternatively, we and others have reported on the use of catalyst-directing groups which bind covalently but reversibly to the substrate.[9, 10, 11] Thus, we identified diphenylphosphinites as ideal systems for the reversible transesterification of alcohols under hydroformylation conditions. Hence, a highly regioselective hydroformlyation of homoallylic alcohols could be realized using this catalyst system to furnish g-lactols in excellent yields (Scheme 1a).[9] The basis for the observed high regioselectivity is the preference for the transition state of an intramolecular 6-exo-trig hydrometallation over that of the 7-endo-trig alternative. Here, the functional hydroxy group to which the directing group is bound has a 1, 3-relation to the reacting functional group; this is the maximum distance ever reported in directed hydroformylation to achieve efficient substrate control.[2] We herein report that it is possible to shift the hydroxy function to which the directing group becomes bound yet one more atom further away from the reacting functional alkene group into a remote 1, 4-relation (Scheme 1b) and still get excellent levels of both regioselectivity and diastereoselectivity in the course of the hydroformylation. This can serve in the atom-economical preparation of a wide range of d-lactols and lactones and even structural units of polypropionate natural products, all of which are important building blocks in organic synthesis.We began our studies on hydroformylation of pent-4-en-1-ol (1) employing the reaction conditions we developed previously for the position-selective hydroformylation of homoallylic alcohols (Table1). To our surprise, a smooth hydroformylation reaction was observed with excellent levels of regioselectivity in favor of the branched product, the dlactol 2 (Table 1, entry 1). However, the reaction was slower than in the case of homoallylic alcohols, and thus conversion