Efficient Chiral N-Heterocyclic Carbene/Copper(I)-Catalyzed Asymmetric Allylic Arylation with Aryl Grignard Reagents
Efficient Chiral N-Heterocyclic Carbene/Copper(I)-Catalyzed Asymmetric Allylic Arylation with Aryl Grignard Reagents
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DOI：
10.1002/anie.200904676
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发表时间：
2009-01-01
影响因子：
16.6
通讯作者：
Tomioka, Kiyoshi
中科院分区：
文献类型：
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作者：
Selim, Khalid B.;Matsumoto, Yasumasa;Tomioka, Kiyoshi
铜催化的不对称烯丙基烷基化反应是获得光学活性化合物的一种有效的C？C键形成反应。[1]使用硬烷基亲核试剂，如Grignard或有机锌试剂，通常产生具有良好区域和对映体选择性的SN2‘产物(g产物)。[2]相反，用芳基金属亲核剂取代时，区域和对映体选择性不足且产率低。[3，4]2007年，Hoveyda和他的同事报道了在非常具体的乙烯基硅烷底物上与有机锌试剂进行高度区域和不对称选择性芳基化反应。还没有关于芳基金属试剂与铜催化的肉桂型底物的不对称烯丙基芳基化反应(AAAR)的成功报道，[6]尽管生成的具有两个芳基的三取代碳原子是一个重要的结构基序，它经常存在于药物(例如舍曲林[7]和托特罗定[8])、生物活性化合物(例如吲哚青碱[9])和天然产物(例如鬼臼毒素[10])中。最近，我们报道了一种用手性氨基膦L1-铜(I)催化剂催化芳基溴化镁合成脂肪族烯丙基溴化物的方法，获得了高的区域选择性和对映体选择性(最高可达81%ee)。然而，肉桂型底物的反应具有较差的g选择性(g/a 16：84)(方案1)。[11]在这里，我们报道了一种强有力的方法，通过以新设计的手性N-杂环卡宾(NHC)[12]-铜(I)络合物C2(图1)有效地催化芳基溴化镁到肉桂型底物的对映选择性合成一系列二芳基乙烯基甲烷。在±788℃下，将用CH2Cl2(0.25mL)稀释的0.20mL，0.6 mmoL)加入4-氯肉桂基溴(1a；0.50 mmoL)的CH2Cl2溶液中，在±788℃下，在15分钟内加入。在噻吩甲酸铜(CuTC)存在下，用nBuLi(6.6mol%)对相应的咪唑烷盐L2-4进行去质子化，制备了NHC-Cu催化剂(2mo%)。由氮原子上带有苯基的L2[12]衍生的催化剂提供的g-2a对映体选择性差(29%ee)，g选择性低(g/a 27：73)。从L3衍生的催化剂，具有均三甲基甲基取代基，[12]主要得到产物a-2a，少量g-2a，ee为31%(g/a4：96)。值得庆幸的是，原位合成的L4-Cu催化剂具有较高的对映选择性(95%ee)和中等的区域选择性.
Copper-catalyzed asymmetric allylic alkylation is an efficient CÀC bond-forming reaction for obtaining optically active compounds.[1] The use of hard alkyl nucleophiles such as Grignard or organozinc reagents usually produces SN2’products (g products) with excellent regio-and enantioselectivity.[2] In contrast, substitution with aryl metal nucleophiles produces insufficient regio-and enantioselectivity as well as low yield.[3, 4] In 2007, Hoveyda and co-workers reported highly regio-and enantioselective arylation with organozinc reagents on very specific vinylsilane substrates.[5] To date, however, there have been no reports of successful coppercatalyzed asymmetric allylic arylation (AAAr) of cinnamyltype substrates with aryl metal reagents,[6] even though the resulting trisubstituted carbon atom having two aryl groups is an important structural motif which is often found in pharmaceuticals (eg, sertraline [7] and tolterodine [8]), biologically active compounds (eg, indatraline [9]), and natural products (eg, podophyllotoxin [10]). Recently, we reported a catalytic AAAr of arylmagnesium bromide to aliphatic allylic bromides, using a chiral amidophosphane L1–copper (I) catalyst, to afford high regioand enantioselectivity (up to exclusive g selectivity, 81% ee). The reactions of cinnamyl-type substrates, however, had poor g selectivity (g/a 16: 84)(Scheme 1).[11] Herein, we report a powerful method for enantioselective synthesis of a range of diarylvinylmethanes by unprecedented AAAr of arylmagnesium bromides to cinnamyl-type substrates efficiently catalyzed by a newly designed chiral N-heterocyclic carbene (NHC)[12]–copper (I) complex C2 (Figure 1).[13]As illustrated in Table1, a diethyl ether solution of PhMgBr (3m; 0.20 mL, 0.6 mmol) diluted with CH2Cl2 (0.25 mL) was added over a 15 minute period to a solution of 4-chlorocinnamyl bromide (1a; 0.50 mmol) in CH2Cl2 (1 mL) at À788C. NHC–Cu catalysts (2 mol%) were prepared in situ by deprotonating the corresponding imidazolidinium salts L2–4 with nBuLi (6.6 mol%) in the presence of copper thiophenecarboxylate (CuTC). The catalyst derived from L2,[12] having a phenyl group on the nitrogen atom, afforded g-2a with poor enantioselectivity (29% ee) and low g selectivity (g/a 27: 73). The catalyst derived from L3, having a mesitylmethyl substituent,[12] gave mostly a product a-2a with a slight amount of g-2a having a 31% ee (g/a 4: 96). Fortunately, the in situ prepared L4–Cu catalyst exhibited high enantioselectivity (95% ee) with moderate regioselec-