Haloboration of internal alkynes with boronium and borenium cations as a route to tetrasubstituted alkenes.
Haloboration of internal alkynes with boronium and borenium cations as a route to tetrasubstituted alkenes.
复制标题
用硼和硼阳离子的内藻类的磨蚀性，作为通往四碱烷烃的途径。
DOI：
10.1002/anie.201302609
复制
发表时间：
2013-07-15
影响因子：
16.6
通讯作者：
Ingleson, Michael J.
中科院分区：
文献类型：
--
作者：
Lawson, James R.;Clark, Ewan R.;Cade, Ian A.;Solomon, Sophia A.;Ingleson, Michael J.
乙烯基硼酸酯是非常有用的前体，特别是用于通过交叉偶联和共轭加成反应形成新的C13 C键。[1，2]虽然炔硼氢化是一种强有力的合成路线，[3，4]但它不适用于三取代乙烯基硼酸酯的合成。因此，需要替代的区域特异性和立体特异性方法，特别是对于随后用于形成四取代烯烃[5-7]，因为通过经典方法生产这些重要的生物活性化合物作为单一异构体是具有挑战性的。[8]三取代乙烯基硼酸酯的一种简单方法是通过金属催化的1，2-碳硼化[9-13]和1，1-碳硼化来官能化内部炔。[14]将两个可选择性转化的部分引入到内部炔上应该能够通过连续的交叉偶联反应容易地获得四取代的烯烃。在这一领域已经取得了重大进展，特别是在双金属化的内部炔，以提供两个亲核位点的不同的反应活性。[15-19]内炔的卤硼化是二金属化的一种有吸引力的替代方法，因为它产生含有亲核和亲电子位置的矛盾合成中间体。[20]这些合成中间体非常适合于四取代烯烃的多样性定向合成。迄今为止，三卤化硼（BX 3）的炔卤代硼化反应的应用仅限于末端炔，并已被证明是一种有效的路线，以生产具有良好的区域和立体选择性的三取代烯烃。[21-25]内炔的卤代硼化用BCl 3是不成功的，并且它要么是缓慢的[25]，要么在使用BBr 3时产生易受BBr C键断裂影响的异构体混合物。[21最近的计算发现，内炔与BCl 3的卤硼化是吸热的，但随着BX 3的刘易斯酸性增加（Cl< Br< I），卤硼化变成放热的，并且关键过渡态的能量也降低。[27]这一结果表明，在硼的亲电性的增加超过BX 3将促进内炔的卤代硼化。在Friedel-Crafts反应的硼类似物中，三配位[X2 BL]+硼阳离子（称为borenium阳离子; X=卤化物，L=胺）[28，29]是比BX 3对芳烃亲核试剂强得多的亲电试剂。[30因此，预期Borenium阳离子对其他π亲核试剂具有高度反应性，并且最近关于Borenium离子催化的烯烃硼氢化的报道支持这一前提。[32]然而，当炔和[X2 BL]+组合时，可能出现超出所需炔卤代硼化的一系列结果。通过类比受抑刘易斯对（FLP）的反应性，[33]脱硼和刘易斯碱加成也是可行的（方案1）。我们设想，其中刘易斯碱在整个反应中强烈地与硼配位的系统将有利于炔的卤代硼化，因为连续的碱配位排除了游离碱的存在，而游离碱对于硼氢化和刘易斯碱加成都是必不可少的。[30]在此，我们报告，硼阳离子为基础的内炔卤硼化确实是可能的，并进行了良好的区域和立体选择性。由卤代硼化、酯化和交叉偶联组成的反应序列被证明是一种有效的路线，用于构建重要的四取代烯烃药物分子类似物的异构纯形式。我们选择2-（N，N-二甲基氨基）吡啶（2-DMAP）作为理想的胺，因为它是廉价的，强亲核的，并且对C3 N裂解反应具有鲁棒性。[34][X2B（2.
Vinyl boronates are extremely useful precursors, especially for the formation of new CÀC bonds by cross-coupling and conjugate addition reactions.[1, 2] Although alkyne hydroboration is a powerful synthetic route,[3, 4] it is not applicable to the synthesis of trisubstituted vinyl boronates. Thus, alternative regio-and stereospecific methods are needed, particularly for subsequent use in the formation of tetrasubstituted alkenes,[5–7] as the production of these important biologically active compounds as single isomers by classical methods is challenging.[8] One simple approach to trisubstituted vinyl boronates is the functionalization of internal alkynes by metal-catalyzed 1, 2-carboboration [9–13] and 1, 1-carboboration.[14] The introduction of two selectively transformable moieties onto an internal alkyne should enable ready access to tetrasubstituted alkenes by successive cross-coupling reactions. Significant progress has been made in this area, particularly in the dimetalation of internal alkynes to provide two nucleophilic sites of distinct reactivity.[15–19] The haloboration of internal alkynes is an attractive alternative to dimetalation, as it generates ambivalent synthetic intermediates that contain both a nucleophilic and an electrophilic position.[20] These synthetic intermediates are ideally suited for the diversity-oriented synthesis of tetrasubstituted alkenes. To date, the application of alkyne haloboration with boron trihalides (BX3) has been limited to terminal alkynes, and has proved an effective route to produce trisubstituted alkenes with excellent regio-and stereoselectivity.[21–25] The haloboration of internal alkynes is unsuccessful with BCl3, and it is either slow [25] or produces isomeric mixtures susceptible to BÀC bond cleavage when BBr3 is used.[21, 26] Recent calculations found that the haloboration of internal alkynes with BCl3 is endothermic, but as the Lewis acidity of BX3 increases (Cl< Br< I), haloboration becomes exothermic, and the energy of the key transition state is also reduced.[27] This result suggested that an increase in the electrophilicity at boron beyond that of BX3 would facilitate the haloboration of internal alkynes. In the boron analogue of the Friedel–Crafts reaction, three-coordinate [X2BL]+ borocations (termed borenium cations; X= halide, L= amine)[28, 29] were considerably stronger electrophiles towards arene nucleophiles than BX3.[30, 31] Borenium cations were thus expected to be highly reactive towards other π nucleophiles, and a recent report on borenium-ion-catalyzed alkene hydroboration supports this premise.[32] However, when an alkyne and [X2BL]+ are combined, a range of outcomes are possible beyond the desired alkyne haloboration. By analogy to the reactivity of frustrated Lewis pairs (FLPs),[33] both dehydroboration and Lewis base addition are also feasible (Scheme1). We envisaged that systems in which the Lewis base coordinates strongly to boron throughout the reaction would favor the haloboration of alkynes, as continuous base coordination precludes the presence of a free base, which is essential for both dehydroboration and Lewis base addition.[30] Herein we report that the borocation-based haloboration of internal alkynes is indeed possible and proceeds with excellent regio-and stereoselectivity. A reaction sequence consisting of successive haloboration, esterification, and cross-coupling is demonstrated as an effective route for the construction of analogues of important tetrasubstituted-alkene drug molecules in isomerically pure form.We chose 2-(N, N-dimethylamino) pyridine (2-DMAP) as an ideal amine, as it is inexpensive, strongly nucleophilic, and robust to CÀN cleavage reactions.[34][X2B (2 …
登录
查看更多内容
影响因子：
4.9
作者：
Kehr, Gerald;Erker, Gerhard
通讯作者：
Erker, Gerhard
影响因子：
4.9
作者：
Daini, Masaki;Suginome, Michinori
通讯作者：
Suginome, Michinori
影响因子：
15
作者：
Shimizu, M;Nakamaki, C;Hiyama, T
通讯作者：
Hiyama, T
影响因子：
2.8
作者：
Okuno, Yuri;Yamashita, Makoto;Nozaki, Kyoko
通讯作者：
Nozaki, Kyoko
影响因子：
15
作者：
Prokofjevs A;Boussonnière A;Li L;Bonin H;Lacôte E;Curran DP;Vedejs E
通讯作者：
Vedejs E