1,3-Diethynylallenes (DEAs): Enantioselective Synthesis, Absolute Configuration, and Chiral Induction in 1,1,4,4-Tetracyanobuta-1,3-dienes (TCBDs)
1,3-Diethynylallenes (DEAs): Enantioselective Synthesis, Absolute Configuration, and Chiral Induction in 1,1,4,4-Tetracyanobuta-1,3-dienes (TCBDs)
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DOI：
10.1002/chem.200801456
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发表时间：
2008-01-01
影响因子：
4.3
通讯作者：
Diederich, Francois
中科院分区：
文献类型：
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作者：
Alonso-Gomez, Jose Lorenzo;Schanen, Patrick;Diederich, Francois
1875年van t Hoff预测，在偶数个双键的累积烯中，四个取代基必须排列在两个垂直的平面上。[1]Van t Hoff的建议暗示，当适当取代时，烯必须是手性的。[2]当1935年第一个旋光活性的烯被描述时，预测得到了证实。[3]对于1，3-二甲基烯，Roth等人确定了导致外消旋的旋转异构化的活化热。1952年，Celmer和Solomons认识到在自然界中也存在光学活性的联烯。从那时起，人们发现了许多天然的手性联烯。[5]ΔH=45.07kcal摩尔±1。今天，烯烃是有机合成中用途广泛的起始原料和中间体，因为它们的双键参与了所有类型的加成过程，其末端的酸性C±H键很容易被官能团取代，其轴手性在立体选择性合成中被越来越多地利用。[6]我们参与了通过氧化乙炔偶联制备乙炔基烯[7a-c]作为构建线性[8]和大环[7d，9]富碳支架的构建块。在合成了第一系列稳定的1，3-二乙炔基烯(DEAS)之后，我们继续制备了带有烯丙叉碳骨架的形状持久的大环。[7D]虽然DEAS是轴向手性的，但我们组以前曾使用外消旋混合物作为乙酰基支架。最近，我们报道了丙炔2a与光学纯丙酸双丙酯(S)-3在钯作用下发生SN2‘型交叉偶联反应，以25%的产率合成了光学富集型DEA 1a，对映体比(Er)[10]为89：11。[8]与先前报道的对映选择性[11]和非对映选择性[12]Pd介导的SN2’型交叉偶联反应一样，我们将丙烯的绝对构型暂定为(P)。在这里，我们给出了X射线结晶学证据，证明了钯催化的炔烃2与(S)-3的不对称加成反应实际上是在相反的立体控制下进行的，从而得到了(M)-1，从而为钯介导的不对称合成SN2‘型交叉偶联反应提供了第一个例子。结果表明，4-N，N-二甲基苯胺(DMA)给电子体取代的光学活性DEAS发生了光异构化反应，导致外消旋反应。它们还与四氰基乙烯(TCNE)[13]以简单的[2+2]环加成反应生成光学活性的、光稳定性的1，1，4，4-四氰基丁酸-1，3-二烯(TCBD)衍生物。在这些化合物中，用圆二色谱(CD)观察到TCBD发色团中光学活性的联烯部分的手性诱导。首先，我们进行了进一步的研究，以提高以前报道的光学活性DEAS的合成的产率和对映体选择性。[8]使用具有不同保护基团的炔烃2a，b来实现选择性去保护，提供随后以受控方式获得低聚物的途径(方案1，表1)。Me_3Si保护的DEA_1a的Er用Mosher酸氯[8]衍生化，1b的Er用nBu4Nf/THF去除iPr3Si基团后，在手性固定相(CSP)Glk-O1(正己烷/0.25%iPrOH)上循环高效液相色谱法测定(见支持信息)。将碱量从0.4当量增加到2.1当量对于在不影响对映体选择性的情况下显著提高产率是必不可少的(条目1和2，表1)。当使用丙酮保护的乙炔2b时，观察到反应活性较低。将温度从30摄氏度提高到508摄氏度
In 1875 van t Hoff predicted that in cumulenes with an even number of double bonds the four substituents must be arranged in two perpendicular planes.[1] Van t Hoff’s proposal implied that allenes must be chiral when appropriately substituted.[2] The predictions were confirmed when the first optically active allenes were described in 1935.[3] For 1, 3-dimethylallene, the activation enthalpy for rotational isomerism leading to racemization was determined by Roth et al. as ΔH= 45.07 kcal molÀ1.[4] In 1952, Celmer and Solomons recognized that optically active allenes also occur in nature.[5] Since then, a number of natural chiral allenes have been found. Today, allenes are versatile starting materials and intermediates in organic synthesis because their double bonds participate in all types of addition processes, their terminal, acidic CÀH bonds are easily replaced by functional groups, and their axial chirality is increasingly exploited in stereoselective synthesis.[6] We have been involved in the preparation of ethynylated allenes [7a–c] as building blocks for the construction of linear [8] and macrocyclic [7d, 9] carbon-rich scaffolds through oxidative acetylenic coupling. Following the synthesis of a first series of stable 1, 3-diethynylallenes (DEAs), we proceeded with the preparation of shape-persistent macrocycles with allenoacetylenic carbon backbones.[7d] Although DEAs are axially chiral, racemic mixtures were previously used in our group for acetylenic scaffolding. Recently, we reported the synthesis of optically enriched DEA 1a in 25% yield and with an enantiomer ratio (er)[10] of 89: 11 by Pd-mediatedSN2’-type cross-coupling of alkyne 2a with the optically pure bispropargylic ester (S)-3.[8] The absolute configuration of the allene was tentatively assigned as (P) on the basis of an anti-SN2’-type addition of 2a to (S)-3, as previously reported for enantioselective [11] and diastereoselective [12] Pd-mediated SN2’-type cross-coupling reactions. Here, we give X-ray crystallographic evidence that the enantioselective Pd-mediated addition of alkynes 2 to (S)-3 actually proceeds under opposite stereocontrol, leading to (M)-1, thereby providing the first example for a Pd-mediated enantioselective syn-SN2’-type cross-coupling reaction. We show that 4-N, N-dimethylanilino (DMA) donor-substituted optically active DEAs undergo photoisomerization leading to racemization. They also react in a facile [2+ 2] cycloaddition with tetracyanoethene (TCNE)[13] to form, after retrocycloaddition, optically active, photostable 1, 1, 4, 4-tetracyanobuta-1, 3-diene (TCBD) derivatives. In these compounds, chiral induction from the optically active allene moiety in the TCBD chromophore is observed by circular dichroism (CD) spectroscopy. First, we undertook further studies to improve both the yield and the enantioselectivity of the previously reported synthesis of optically active DEAs.[8] Alkynes 2a, b with different protecting groups were used to enable selective deprotection, providing subsequent access to oligomers in a controlled manner (Scheme 1, Table 1). The er of Me3Siprotected DEA 1a was determined after derivatization with the Mosher acid chloride [8] and the er of 1b by recycling HPLC on the chiral stationary phase (CSP) WHELK-O1 (hexane/0.25% iPrOH) after removal of the iPr3Si group with nBu4NF/THF (see Supporting Information). Increasing the amount of base from 0.4 to 2.1 equiv was essential to improve the yield considerably without affecting the enantioselectivity (entries 1 and 2, Table 1). When the acetonide-protected acetylene 2b was used, a lower reactivity was observed. Raising the temperature from 30 to 508C