Structure-Based Rationale for Selectivity in the Asymmetric Allylic Alkylation of Cycloalkenyl Esters Employing the Trost 'Standard Ligand' (TSL): Isolation, Analysis and Alkylation of the Monomeric form of the Cationic η3-Cyclohexenyl Complex [(η3-c-C6H9)Pd(TSL)]+
Structure-Based Rationale for Selectivity in the Asymmetric Allylic Alkylation of Cycloalkenyl Esters Employing the Trost 'Standard Ligand' (TSL): Isolation, Analysis and Alkylation of the Monomeric form of the Cationic η3-Cyclohexenyl Complex [(η3-c-C6H9)Pd(TSL)]+
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DOI：
10.1021/ja8099757
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发表时间：
2009-07-29
影响因子：
15
通讯作者：
Schramm, York
中科院分区：
文献类型：
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作者：
Butts, Craig P.;Filali, Emane;Schramm, York
通过核磁共振、同位素标记和计算确定了含反式环己二胺的阳离子Pd-ETA(3)-烯丙基和Pd-ETA(3)-环己烯基络合物[Pd(R，R)-1(ETA(3)-C3H5)](+)(7(+))和[Pd(R，R)-1(ETA(3)-C6H9)](+)(8(+))的溶液相结构。在这两种配合物中，(R，R)-1都采用C-1对称构象，导致13元络合物呈凹形，其中手性支架中的一个酰胺基团在靠近一个烯丙基末端的凹面外伸出其NH单元。相邻的酰胺具有相反的取向，并且在相对的烯丙基末端附近从凹面伸出其羰基。[8(+)][X-]的化学计量和催化不对称烷基化反应(E=酯，M=‘护航’反离子，X=Pd烯丙基反离子)表现出与已报道的原位生成催化剂相同的选择性和趋势，并从计算上探索了一个新的对映选择性模型。发现三个因素控制了亲核试剂攻击8(+)中的ETA(3)-C6H9环的区域选择性(亲S vsPro-R)，从而控制了烷基化产物的ee：(I)ETA(3)-C6H9部分与配体的一个苯环的空间相互作用导致了亲R的扭转选择性偏向；(Ii)亲核试剂S的亲核传递可以通过与凹取向酰胺N-H的氢键来促进；以及(Iii)亲核分子的亲R传递可以通过护送离子(M)与凹取向酰胺羰基的结合来促进。后两种相反的相互作用导致烷基化反应的选择性对X-和M+的同一性很敏感。对环己烯酯底物生成8(+)的反应也进行了计算探索。凹面取向的酰胺N-H能够通过氢键与烯丙基酯的羰基结合来激活烯丙基酯的离开基团。然而，这种相互作用只对底物的(S)-对映体是可行的，导致预测了一个强大的动力学拆分(k(S)>；>；k(R))，正如实验所发现的那样。这个新的模型包含了两个区域化学位置不同的(NH)和(CO)位置，用于疏核或亲核结合，可以广泛用于解释(R，R)-1的钯配合物及其相关配体催化的不对称烯丙基烷基化反应的选择性。
The solution-phase structures of the monomeric forms of the cationic Pd-eta(3)-allyl and Pd-eta(3)-cyclohexenyl complexes [Pd(R,R)-1(eta(3)-C3H5)](+) (7(+)) and [Pd(R,R)-1(eta(3)-C6H9)](+) (8(+)) bearing the trans-cyclohexylenediamine-based Trost 'Standard Ligand' (R,R)-1 have been elucidated by NMR, isotopic labeling and computation. In both complexes, (R,R)-1 is found to adopt a C-1-symmetric conformation, leading to a concave shape in the 13-membered chelate in which one amide group in the chiral scaffold projects its NH unit out of the concave surface in close vicinity to one allyl terminus. The adjacent amide has a reversed orientation and projects its carbonyl group out of the concave face in the vicinity of the opposite allyl terminus. Stoichiometric and catalytic asymmetric alkylations of [8(+)][X-] by MCHE2 (E = ester, M = 'escort' counterion, X = Pd allyl counterion) show the same selectivities and trends as have been reported for in situ-generated catalysts, and a new model for the enantioselectivity has been explored computationally. Three factors are found to govern the regioselectivity (pro-S vs pro-R) of attack of nucleophiles on the eta(3)-C6H9 ring in 8(+) and thus the ee of the alkylation product: (i) a pro-R torquoselective bias is induced by steric interaction of the eta(3)-C6H9 moiety with one phenyl ring of the ligand; (ii) pro-S delivery of the nucleophile can be facilitated by hydrogen-bonding with the concave orientated amide N-H; and (iii) pro-R delivery of the nucleophile can be facilitated by escort ion (M) binding to the concave orientated amide carbonyl. The latter two opposing interactions lead to the selectivity of the alkylation being sensitive to the identities of X- and M+. The generation of 8(+) from cyclohexenyl ester substrate has also been explored computationally. The concave orientated amide N-H is able to activate the leaving group of the allylic ester by hydrogen bonding to its carbonyl group. However, this interaction is only feasible for the (S)-enantiomer of substrate, leading to the prediction of a powerful kinetic resolution (k(S) >> k(R)), as is found experimentally. This new model involving two regiochemically distinct (NH) and (CO) locations for nucleofuge or nucleophile binding, may prove of broad utility for the interpretation of the selectivity in asymmetric allylic alkylation reactions catalyzed by Pd complexes of (R,R)-1 and related ligands.