CN114669333B - 一种催化α-季碳醛脱羰氢化的催化剂体系和催化方法 - Google Patents

一种催化α-季碳醛脱羰氢化的催化剂体系和催化方法 Download PDF

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CN114669333B
CN114669333B CN202210439122.5A CN202210439122A CN114669333B CN 114669333 B CN114669333 B CN 114669333B CN 202210439122 A CN202210439122 A CN 202210439122A CN 114669333 B CN114669333 B CN 114669333B
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李苏华
李勃
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Sun Yat Sen University
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Abstract

本申请属于α‑季碳醛催化技术领域，尤其涉及一种催化α‑季碳醛脱羰氢化的催化剂体系和催化方法。本申请第一方面提供了一种催化α‑季碳醛脱羰氢化的催化剂体系，由金属铱和BIPHEP配体组成。本申请第二方面提供了一种催化α‑季碳醛脱羰氢化的方法，包括以下步骤：将α‑季碳醛与溶剂混合，在催化剂存在的条件下进行加热反应，得到与所述α‑季碳醛对应的醛基α位由季碳转化成一个次甲基且其手性碳构型保持的产物；所述催化剂由金属铱和BIPHEP配体组成。本申请提供的催化剂体系和催化方法，可有效解决现有仍没有一种高效的、官能团兼容性良好的对大位阻α‑季醛脱羰氢化的催化方法。

Description

一种催化α-季碳醛脱羰氢化的催化剂体系和催化方法
技术领域
本申请属于过渡金属催化的有机合成技术领域，尤其涉及一种催化α-季碳醛脱羰氢化的催化剂体系和催化方法。
背景技术
醛类化合物是一类重要的化合物，是非常容易获得的大宗化学品之一并且其在药物、食品、饲料领域也有良好的应用前景。醛也是一类活性官能团，可以发生多种化学反应：氧化、还原、偶联、缩合以及加成等反应；同时醛基或者醛基与胺类作用（原位形成亚胺）可以作为一个导向基，在金属催化条件下可以实现导向氟化、胺化、硼化、烷基化、芳基化等转化，当实现这些转化后作为导向基的醛基需要脱除。所以发展一种对醛进行高效脱除的策略具有重要意义，而对于α-手性季醛的化合物脱羰后产物手性可以保持将更加具有挑战性。
目前文献报道醛脱羰常用的催化剂是wilkinson催化剂，其在脂肪醛与芳香醛脱羰都展现出良好的催化性能(Tsuji, J. et al. Tetrahedron Lett. 1965, 6, 3969;Ohno, K. et al. J. Am. Chem. Soc. 1968, 90, 99. )，但是催化剂用量需要大于一个当量，此催化剂价格昂贵，所以限制了其使用。另外一个醛脱羰催化效率比较高的体系是Rh/dppp (Doughty, D. H. et al. J. Am.Chem. Soc. 1978, 100, 7083.)，此催化体系对苯甲醛脱羰TON最高可达1×105以上。虽然该催化体系展现出了极高的催化效率，但是对于大位阻α-季醛脱羰没有任何催化效果。对大位阻的α-季醛脱羰反应，到目前为止只有一篇文献报道，该文献报道了Pd/C催化金刚烷甲醛脱羰生成金刚烷的反应(T. Shirai etal. Synlett 2019 30 972-976.)。该催化体系虽然实现了α-季醛的脱羰，但是底物仅仅适用于结构特殊的金刚烷甲醛。除了底物特殊外，该反应需要比较高的催化剂上载量（10%mol Pd/C）与较长的反应时间（48.0 h）。Iwai 等人报道了一例[IrCl(cod)]2 (5 mol% Ir)与三苯基膦共催化α-季碳醛脱羰氢化，其唯一的底物产率仅3%的产物(T. Iwai et al.Chem. Commun., 2008, 6215)。
到目前为止，对大位阻α-季醛脱羰还没有一种高效的、官能团兼容性良好的催化体系被开发出来，特别是对于α-手性季醛脱羰后产物手性保持的方法更是亟待研究。
发明内容
鉴于此，本申请提供了一种催化α-季碳醛脱羰氢化的催化剂体系和催化方法，可有效解决现有仍没有一种高效的、官能团兼容性良好的对大位阻α-季醛脱羰氢化的催化方法。
本申请第一方面提供了一种催化α-季碳醛脱羰氢化的催化剂体系，由金属铱和BIPHEP配体组成；
所述金属铱为[Ir(COD)Cl]2或/和[Ir(COE)Cl]2；
所述BIPHEP配体选自(6,6'-二甲氧基联苯-2,2'-基)双(二苯基膦)、(6,6′-二甲氧基联苯-2,2′-二基)二[双(4-甲氧基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二甲氧基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二甲基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二叔丁基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二苯基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二三氟甲基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,4,5-三氟苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,4,5-三甲氧基苯基)膦]、(6,6'-二甲氧基联苯-2,2'-基)双(二异丙基膦)、1,1'-联萘-2,2'-双二苯膦、5,5'-双(二苯基磷)-4,4'-二-1,3-苯并二氧和[(5,6),(5',6')-双(乙烯二氧)联苯-2,2'-基]二苯基磷中的一种或多种。
优选的，所述金属铱和所述BIPHEP配体的摩尔比为1 : (0.5~3)。
进一步的，所述α-季碳醛具有式I所示结构；
Figure SMS_1
式I；
其中，R1、R2和R3各自独立地为取代或非取代烷基、取代或非取代环烷烃、取代或非取代杂环烷烃。
进一步的，所述α-季碳醛为通过式II原位脱除一分子的氢气产生如所述式I中的醛基，所述原位脱除一分子的氢气的催化剂采用脱除羰基相同的催化剂（即所述催化剂体系）。
Figure SMS_2
式II；
其中，R1、R2和R3各自独立地为取代或非取代烷基、取代或非取代环烷烃、取代或非取代杂环烷烃。
进一步的，所述α-季碳醛选自直链α-季碳醛、环状α-季碳醛以及含有杂原子的α-季碳醛中的一种或多种。
更进一步的，所述R1、所述R2和所述R3各自独立地选自卤素、C1～12烷基、C1～12卤代烷基、C1～12芳基取代烷基、C1～12氨基取代烷基、C1～12烷氧基取代烷基、C1～12吡啶取代烷基、C1～12噻吩取代烷基、C1～12呋喃取代烷基、C3～12环烷基、C3～12氨基取代环烷基、C12～18稠和环；其中的杂原子为N和O卤素中的一种或多种，一个或多个。
优选的，所述α-季碳醛选自：
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中的一种或多种。
本申请第二方面提供了一种催化α-季碳醛脱羰氢化的方法，包括以下步骤：
将α-季碳醛与溶剂混合，在催化剂存在的条件下进行加热反应，得到与所述α-季碳醛对应的醛基α位手性碳构型保持产物；所述催化剂为所述催化剂体系；所述α-季碳醛为上述种类的α-季碳醛。
具体的，所述醛基α位手性碳构型保持产物为与所述α-季碳醛对应的醛基α位由季碳转化成一个次甲基且其手性碳构型保持的产物。
具体的，所述催化α-季碳醛脱羰氢化的方法路线如下：
Figure SMS_27
。
具体的，由上述反应可知，所述R1、所述R2和所述R3均不参与反应，同时对上述脱羰反应也不产生任何的影响，因此只需式I所示化合物中存在醛基，在上述催化剂体系中，即可发生上述脱羰反应。
优选的，所述α-季碳醛、所述金属铱与所述BIPHEP配体的摩尔比为100:(0.1~10):(0.05~30)。
优选的，所述溶剂选自邻二甲苯、间二甲苯、对二甲苯、混合二甲苯、异丙苯、乙苯、叔丁基苯、伞花烃、二乙二醇二甲醚中的一种或多种。优选的，所述加热反应的温度为130~190℃，所述加热反应的时间为5~30小时。
更优选的，所述溶剂为邻二甲苯。
更优选的，所述加热反应的温度为170℃。
具体的，本申请提供的催化α-季碳醛脱羰氢化的方法在开放体系中进行，底物（式I所示化合物）、催化剂体系与溶剂在手套箱进行称量与量取后加入到史莱克反应管，反应管拿出手套箱后用氮气气球保护。
本申请发现以金属铱-BIPHEP为催化体系，实现了大位阻α-季醛脱羰，对于的α-手性季醛可得到醛基α位手性碳构型保持产物的方法。反应条件简单；反应的底物适用性强，对于直链或者环状以及含有杂原子的α-季醛均可实现脱羰；对于的α-手性季醛可得到醛基α位手性碳构型保持产物，并且产率良好。
附图说明
为了更清楚地说明本申请实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍。
图1为本申请提供的催化α-季碳醛脱羰氢化的合成路线；
图2为本申请测试例提供的不同催化剂配体对α-季醛（式1-1所示化合物）脱羰的转化率和收率；
图3为本申请测试例提供的不同α-季碳醛脱羰氢化后得到的醛基α位手性碳构型保持产物结构式和收率结果图；
图4为本申请测试例提供的不同α-季碳醛脱羰氢化后得到的醛基α位手性碳构型保持产物结构式和收率结果图；
图5为本申请测试例提供的不同α-季碳醛结构进行脱羰氢化的收率结果图；
图6为本申请对比例3提供的不同催化剂配体催化α-季碳醛脱羰氢化的转化率和产率结果。
具体实施方式
本申请提供了一种催化α-季碳醛脱羰氢化的催化剂体系和催化方法，用于解决现有技术中没有一种高效的、官能团兼容性良好的对大位阻α-季醛脱羰氢化的催化方法的缺陷。
下面将对本申请实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本申请一部分实施例，而不是全部的实施例。基于本申请中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本申请保护的范围。
本申请实施例所用的α-季碳醛和BIPHEP配体可通过现有文献公开的方法制备得到。
实施例1
本申请实施例提供了式1-1所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_28
。
取一个25 mL史莱克反应管并用高温枪烘干，然后将其移入手套箱，在手套箱中将[Ir(COD)Cl]2(10.3 mg, 0.0153 mmol)，L7 (56.9 mg, 0.0603 mmol)与1-1(303.8 mg,1.0013 mmol)依次加入该反应管中，最后加入o-Xylene (1.5 mL)。温度升到170 ℃反应18小时后，反应液直接柱层析柱层析（PE/EA = 20:1）得到2-1((229.1 mg, 83% yield)，淡黄色油状物。1H NMR(400 MHz, CDCl3) δ 7.32 – 7.23 (m, 3H), 7.23 – 7.15 (m, 1H),7.17 – 7.09 (m, 2H), 4.06 (br. s, 2H), 2.63 (t,J= 12.8 Hz, 2H), 2.53 (d,J=7.0 Hz, 2H), 1.81 – 1.53 (m, 3H), 1.45 (s, 9H), 1.14 (qd,J= 12.6, 4.2 Hz,2H)。13C NMR(101 MHz, CDCl3) δ 154.99, 140.36, 129.23, 128.35, 126.05, 79.33,44.11, 43.27, 38.30, 32.11, 28.59。MS (EI): m/z (%) 275 (M+, 2.97), 57 (100)。
实施例2
本申请实施例提供了式1-2所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_29
。
参考实施例1，[Ir(COD)Cl]2(10.2 mg, 0.0152 mmol), L7 (56.8 mg, 0.0602mmol.),1-2 (338.2 mg, 1.0023 mmol.), o-Xylene (1.5 mL)，170 ℃反应18小时。柱层析（PE/EA = 10:1）得到2-2(290.1 mg, 94%)，白色固体。1H NMR(400 MHz, CDCl3) δ 7.41– 7.23 (m, 7H, 7.24 – 7.15 (m, 1), 7.16 – 7.08 (m, 2), 5.12 (s, 2), 4.16 (br.s, 2H), 2.72 (m, 2H), 2.54 (d,J= 7.0 Hz, 2H), 1.84 – 1.53 (m, 3H), 1.25 –1.06 (m, 2H)。13C NMR(101 MHz, CDCl3) δ 155.37, 140.17, 137.07, 129.21, 128.56,128.36, 128.00, 127.92, 67.03, 44.29, 43.18, 38.16, 31.99。IR(neat): 2926,2854, 1691, 1240, 1185, 1060 cm-1。MS (EI): m/z (%) 275 (M+, 2.97), 57 (100)。HRMS(ESI+):m/zcalc’d for (M + H)+: 310.1802, found 310.1804。MP: 42.9-43.4 °C。
实施例3
本申请实施例提供了式1-3所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_30
。
参考实施例1，Ir(COD)Cl]2(10.1 mg, 0.0150 mmol.), L7 (56.8 mg, 0.0602mmol.),1-3(308.4 mg, 1.0033 mmol.)，o-Xylene (1.5 mL)，170 ℃反应18小时。柱层析（PE/EA = 10:1）得到2-3((270.2 mg, 96% yield)。1H NMR(400 MHz, CDCl3) δ 7.38 (s,5H), 7.31 – 7.26 (m, 2H), 7.23 – 7.17 (m, 1H), 7.18 – 7.09 (m, 2H), 4.71 (d,J= 12.2 Hz, 1H), 3.72 (d,J= 13.6 Hz, 1H), 3.04 – 2.62 (m, 2H), 2.57 (t,J= 5.6Hz, 2H), 1.99 – 1.71 (m, 2H), 1.59 (d,J= 13.0 Hz, 1H), 1.45 – 0.93 (m, 2H)。13CNMR(101 MHz, CDCl3) δ 170.31, 139.95, 136.44, 129.44, 129.10, 128.42, 128.34,126.86, 126.09, 48.05, 43.03, 42.47, 38.37, 32.69, 31.85。IR(neat): 2916,2850, 1628, 1431, 1284, 966 cm-1。MS (EI): m/z (%) 279 (M+, 41.45), 105 (100)。HRMS(ESI+):m/zcalc’d for (M + H)+: 280.1696, found 280.1694。
实施例4
本申请实施例提供了式1-4所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_31
。
参考实施例1，[Ir(COD)Cl]2(10.0 mg, 0.0149 mmol.), L7 (56.5 mg, 0.0599mmol.),1-4(358.1 mg, 1.0017 mmol.)，o-Xylene (1.5 mL)，170 ℃反应18小时。柱层析（PE/EA = 10:1）得到2-4(316.2 mg, 96% yield)。1H NMR(400 MHz, CDCl3) δ 7.61 (d,J= 8.2 Hz, 2H), 7.29 (d,J= 8.0 Hz, 2H), 7.28 – 7.20 (m, 2H), 7.19 – 7.13 (m,1H), 7.10 – 7.00 (m, 2H), 3.79 – 3.69 (m, 2H), 2.50 (d,J= 6.7 Hz, 2H), 2.41(s, 3H), 2.17 (t,J= 11.8 Hz, 2H), 1.77 – 1.59 (m, 1H), 1.48 – 1.05 (m, 3H)。13CNMR(101 MHz, CDCl3) δ 143.45, 139.91, 133.20, 129.63, 129.09, 128.37, 127.81,126.14, 46.55, 42.72, 37.43, 31.37, 21.60。IR(neat): 2914, 2846, 1336, 1159,937, 814 cm-1。MS (EI): m/z (%) 329 (M+, 31.91), 91(100)。HRMS(ESI+):m/zcalc’dfor (M + H)+: 330.1522, found 330.1519。MP: 97.7 - 98.1 ℃。
实施例5
本申请实施例提供了式1-5所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_32
。
参考实施例1，[Ir(COD)Cl]2(10.0 mg, 0.0149 mmol.), L7 (56.7 mg, 0.0601mmol.),1-5 (228.1 mg, 1.0035 mmol.)，o-Xylene (1.5 mL)，170 ℃反18小时。柱层析（PE/EA = 20:1）得到2-5(139.8 mg, 70%) ，淡黄色油状物。1H NMR(400 MHz, CDCl3) δ4.05 (br. s, 2H), 2.68 (t,J= 12.2 Hz, 2H), 1.65 – 1.54 (m, 1H), 1.53-1.45 (m,10H), 1.08 (qd,J= 12.5, 4.2 Hz, 2H), 0.93 (d,J= 6.5 Hz, 3H).13C NMR(101 MHz,CDCl3) δ 155.05, 79.22, 44.39, 34.16, 31.10, 28.62, 22.01.MS (EI): m/z (%)199 (M+, 3.81), 57 (100)。
实施例6
本申请实施例提供式1-6所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_33
。
参考实施例1，[Ir(COD)Cl]2(10.0 mg, 0.0149 mmol.), L7 (56.7 mg, 0.0601mmol.), aldehyde3-6(347.9 mg, 1.0041 mmol.)，o-Xylene (1.5 mL)，170 ℃反应18小时。柱层析（PE/EA = 20:1）得到2-6(249.8 mg, 78% yield)，淡黄色油状物。1H NMR(400MHz, CDCl3) δ 7.26 – 7.18 (m, 2H), 6.75 – 6.60 (m, 3H), 4.08 (br. s, 2H),3.41 – 3.26 (m, 2H), 2.90 (s, 3H), 2.69 (t,J= 12.0 Hz, 2H), 1.76 – 1.63 (m,2H), 1.60 – 1.46 (m, 3H), 1.45 (s, 9H), 1.15 (qd,J= 12.4, 4.3 Hz, 2H).13C NMR(101 MHz, CDCl3) δ 154.98, 149.33, 129.32, 116.24, 112.36, 79.38, 50.36,44.10, 38.31, 34.19, 32.98, 32.31, 28.60.IR(neat): 2923, 1689, 1600, 1506,1169, 866 cm-1。MS(ESI): m/z (%) 319 (M+H)+, 8.85), 263 (100).HRMS(ESI+):m/ zcalc’d for (M + H)+: 319.2380, found 319.2378。
实施例7
本申请实施例提供式1-7所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_34
。
参考实施例1，[Ir(COD)Cl]2(10.2 mg, 0.0152 mmol.), L7 (56.6 mg, 0.0600mmol.),1-7 (273.3 mg, 1.0071 mmol.)，o-Xylene (1.5 mL)，170 ℃反应24小时。柱层析(PE/EA = 10:1)得到2-7(180.8 mg, 74% yield)，淡黄色油状物。1H NMR(400 MHz,CDCl3) δ 4.07 (br. s, 2H), 3.42 (t,J= 6.2 Hz, 2H), 3.33 (s, 3H), 2.69 (t,J=11.7 Hz, 2H), 1.74 – 1.59 (m, 2H), 1.60 – 1.48 (m, 3H), 1.45 (s, 9H) 1.10(qd,J= 12.4, 4.3 Hz, 2H).13C NMR (101 MHz, CDCl3) δ 154.98, 79.27, 70.26,58.71, 44.06, 36.30, 32.98, 32.23, 28.57.MS (EI): m/z (%) 243 (M+, 0.79), 57(100)。
实施例8
本申请实施例提供式1-8所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_35
。
参考实施例1，[Ir(COD)Cl]2(10.3 mg, 0.0153 mmol.), L7 (56.7 mg, 0.0601mmol.),1-8 (260.8 mg, 1.0057 mmol.)，o-Xylene (1.5 mL)，170 ℃反应18小时。柱层析(PE/EA = 10:1)得到2-8 (187.6 mg, 81% yield)，淡黄色油状物。1H NMR (400 MHz,CDCl3) δ 4.57 (t,J= 5.8 Hz, 1H), 4.46 (t,J= 5.7 Hz, 1H), 4.09 (br. s, 2H),2.68 (t,J= 13.4 Hz, 2H), 1.79 – 1.51 (m, 5H), 1.46 (s, 9H), 1.14 (qd,J= 12.4,4.4 Hz, 2H).13C NMR(101 MHz, CDCl3) δ 154.96, 81.98 (d,J= 164.4 Hz), 79.39,44.01, 37.04 (d,J= 19.4 Hz), 32.60 (d,J= 3.9 Hz), 32.08, 28.57.19F NMR(377MHz, CDCl3) δ -219.18.MS (EI): m/z (%) 231 (M+, 3.86), 57 (100)。
实施例9
本申请实施例提供式1-9所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_36
。
参考实施例1，[Ir(COD)Cl]2(10.1 mg, 0.0150 mmol), L7 (56.9 mg, 0.0603mmol),1-9 (286.6 mg, 1.0044 mmol)，o-Xylene (1.5 mL)，170 ℃反应18小时。柱层析(PE/EA = 10:1)得到2-9(203.2 mg, 79% yield)，无色油状物。1H NMR(400 MHz, CDCl3)δ 4.14 (q,J= 7.1 Hz, 2H), 4.02 (s, 2H), 2.83 (t,J= 11.8 Hz, 2H), 2.43 (tt,J=11.0, 3.8 Hz, 1H), 1.97 – 1.84 (m, 2H), 1.62 (qd,J= 12.9, 12.2, 4.2 Hz, 2H),1.46 (s, 9H), 1.26 (t,J= 7.1 Hz, 3H).13C NMR(101 MHz, CDCl3) δ 174.70, 154.82,79.65, 60.59, 43.17, 41.26, 28.54, 28.08, 14.31.MS (EI): m/z (%) 257 (M+,0.2), 57 (100)。
实施例10
本申请实施例提供式1-10所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_37
。
参考实施例1，[Ir(COD)Cl]2(16.9 mg, 0.0252 mmol), L7 (56.5 mg, 0.1002mmol),1-10 (304.6 mg, 1.0040 mmol)，o-Xylene (1.5 mL)。170 °C 反应 36 小时。柱层析（PE/EA = 20/1）得到2-10 (187.5 mg, 68%)。1H NMR (600 MHz, DMSO-d 6, 80 °C) δ7.29 (t,J= 7.1 Hz, 2H), 7.19 (d,J= 7.5 Hz, 3H), 3.75 (d,J= 13.1 Hz, 2H), 2.82(t,J= 12.0 Hz, 1H), 2.62 – 2.54 (m, 1H), 1.82 – 1.51 (m, 3H), 1.42 – 1.24 (m,10H), 1.18 (q,J= 11.3 Hz, 1H).13C NMR(151 MHz, DMSO-d 6, 80 ℃) δ 154.55,140.45, 129.33, 128.65, 126.32, 78.87, 49.53, 44.66, 39.96, 37.84, 30.86,28.65, 24.94.MS(ESI): m/z (%) 298 (M + Na)+, 100), 298 (100)。
实施例11
本申请实施例提供式1-11所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_38
。
参考实施例1，[Ir(COD)Cl]2(10.2 mg, 0.0152 mmol), L7 (56.5 mg, 0.0599mmol),1-11 (202.5 mg, 1.0010 mmol)，o-Xylene (1.5 mL)，170 °C 反应 24 小时。柱层析（PE = 100%）得到2-11(119.9 mg, 69% yield), 无色油状物。（沸点与二甲苯接近，后处理损失核磁收率90%）。1H NMR (600 MHz, CDCl3) δ 7.26 (t,J= 7.4 Hz, 2H), 7.17 (t,J= 7.3 Hz, 1H), 7.13 (d,J= 7.5 Hz, 2H), 2.47 (d,J= 7.1 Hz, 2H), 1.82 – 1.58(m, 5H), 1.56 – 1.48 (m, 1H), 1.24 – 1.10 (m, 3H), 1.01 – 0.88 (m, 2H).13C NMR(151 MHz, CDCl3) δ 141.51, 129.32, 128.16, 125.69, 44.29, 39.93, 33.30,26.72, 26.47.MS(EI): m/z (%) 174 (M+, 63.62), 91 (100)。
实施例12
本申请实施例提供式1-12所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_39
。
参考实施例1，[Ir(COD)Cl]2(10.3 mg, 0.0153 mmol), L7 (56.8 mg, 0.0602mmol),1-12 (289.9 mg, 1.0 mmol)，o-Xylene (1.5 mL)，170 °C 18小时。柱层析（PE/EA= 10:1）得2-12(211.8 mg, 81%)。1H NMRof Two Rotamers(400 MHz, CDCl3) δ 7.35 –7.26 (m, 2H), 7.21 (t,J= 7.8 Hz, 1H), 7.16 (d,J= 7.5 Hz, 2H), 3.65 – 3.36 (m,2H), 3.25 (hept,J= 9.2, 8.2 Hz, 1H), 3.09 – 2.91 (m, 1H), 2.80 – 2.56 (m,2H), 2.55 – 2.29 (m, 1H), 2.00 – 1.85 (m, 1H), 1.76 – 1.51 (m, 2H), 1.45 (s,9H).13C NMR of Two Rotamers(101 MHz, CDCl3) δ 154.75, 140.44, 128.77, 128.52,126.23, 79.13 and 79.09, 51.35 and 51.09, 45.72 and 45.29, 40.86 and 40.15,39.32, 31.53 and 30.83, 28.63.MS (EI): m/z (%) 261 (M+, 3.23), 57 (100)。
实施例13
本申请实施例提供式1-13所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_40
。
参考实施例1，[Ir(COD)Cl]2(10.1 mg, 0.0150 mmol), L7 (56.8 mg, 0.0602mmol), aldehyde3-16(275.8 mg, 1.0016 mmol)，o-Xylene (1.5 mL)，170 °C 反应18小时。柱层析（PE/EA = 10:1）得到2-13(203.2 mg, 82% yield)，无色油状物。1H NMR (400MHz, CDCl3) δ 7.36 – 7.25 (m, 2H), 7.25 – 7.16 (m, 1H), 7.17 – 7.10 (m, 2H),3.99 (t,J= 8.3 Hz, 2H), 3.65 (dd,J= 8.6, 5.3 Hz, 2H), 3.07 – 2.78 (m, 2H),2.86 – 2.73 (m, 1H), 1.44 (s, 9H).13C NMR(101 MHz, CDCl3) δ 156.57, 139.45,128.68, 128.51, 126.47, 79.34, 54.30, 40.39, 30.00, 28.53. IR(neat): 2964,1684, 1407, 1366, 1135, 862 cm-1。MS (EI): m/z (%) 247 (M+, 2.33), 57 (100)。HRMS(ESI+):m/zcalc’d for (M + H)+: 248.1645, found 248.1644。
实施例14
本申请实施例提供式1-14所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_41
。
参考实施例1，[Ir(COD)Cl]2(10.2 mg, 0.0152 mmol.), L7 (56.7 mg, 0.0601mmol.),1-14(196.5 mg, 1.0055 mmol.)，o-Xylene (1.5 mL)，170 °C 反应18小时。柱层析（PE/EA = 50:1）得到2-14(145.0 mg, 86% yield)，无色油状物。1H NMR(400 MHz,CDCl3) δ 3.63 (s, 3H), 1.84 – 1.68 (m, 6H), 1.66 – 1.52 (m, 7H).13C NMR(151MHz, CDCl3) δ 178.81, 51.67, 38.41, 28.17, 25.49, 23.84. MS (EI): m/z (%) 168(M+, 68.57), 108.9 (100)。
实施例15
本申请实施例提供式1-15所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_42
。
参考实施例1，[Ir(COD)Cl]2(10.1 mg, 0.0150 mmol.), L7 (56.9 mg, 0.0603mmol.),1-15(223.5 mg, 1.0055 mmol.)，o-Xylene (1.5 mL)，170 °C 反应24小时。柱层析（PE/EA = 50:1）得到2-13(168.4 mg, 86% yield)，白色固体。1H NMR(400 MHz, CDCl3)δ 3.65 (s, 3H), 2.01 (s, 3H), 1.89 (d,J= 3.1 Hz, 6H), 1.80 – 1.63 (m, 6H). 13CNMR(101 MHz, CDCl3) δ 178.36, 51.67, 40.83, 38.99, 36.64, 28.08.MS (EI): m/z(%)194 (M+, 14.81), 135 (100)。
实施例16
本申请实施例提供式1-16所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_43
。
参考实施例1，[Ir(COD)Cl]2(10.3 mg, 0.0153 mmol.), L7 (56.5 mg, 0.0599mmol.),1-16(196.5 mg, 1.0055 mmol.)，o-Xylene (1.5 mL)，170 °C反应18小时。2-16与o-Xylene R f 值与沸点接近。核磁收率： 86%。
实施例17
本申请实施例提供式1-17所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_44
。
参考实施例1，[Ir(COD)Cl]2(10.2 mg, 0.0152 mmol), L7 (56.7 mg, 0.0601mmol),1-17 (218.4 mg, 1.0054 mmol.)，o-Xylene (1.5 mL)，170 °C反应18小时。柱层析（PE/EA = 10/1）得到2-17(174.9 mg, 92% yield)。1H NMR(400 MHz, CDCl3) δ 7.81 (dd,J= 5.4, 3.0 Hz, 2H), 7.70 (dd,J= 5.5, 3.1 Hz, 2H), 4.54 (hept,J= 7.0 Hz, 1H),1.49 (d,J= 6.9 Hz, 6H).13C NMR(151 MHz, CDCl3) δ 168.49, 133.86, 132.23,123.09, 43.10, 20.24.MS (EI): m/z (%) 189 (M+, 9.23), 174 (100)。
实施例18
本申请实施例提供式1-18所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_45
。
参考实施例1，[Ir(COD)Cl]2(10.2 mg, 0.0152 mmol.), L7 (56.5 mg, 0.0599mmol.),1-18 (188.5 mg, 1.0067 mmol.) and o-Xylene (1.5 mL)，170 °C反应18小时。柱层析（PE/EA = 20/1）得到2-18(119.3 mg, 74% yield)，淡黄色固体。（沸点低）。1H NMR(600 MHz, CDCl3) δ 4.38 (br. s, 1H), 3.76 (br. s, 1H), 1.44 (s, 9H), 1.13 (d,J= 6.6 Hz, 6H).13C NMR(151 MHz, CDCl3) δ 155.29, 79.05, 42.62, 28.56, 23.23.MS(EI): 101 ((M – C3H9N)+, 36.57), 59 (100)。
实施例19
本申请实施例提供式1-19所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_46
。
参考实施例1，[Ir(COD)Cl]2(10.0 mg, 0.0149 mmol.), L9 (56.8 mg, 0.0602mmol.), aldehyde1-19(294.4 mg, 1.0035 mmol.) in o-Xylene (1.5 mL)，170 °C反应18小时。柱层析（PE/EA = 10/1）得到2-19(218.4 mg, 82% yield)，淡黄色油状物。1H NMR(400 MHz, CDCl3) δ 7.30 (dd,J= 1.9, 0.8 Hz, 1H), 6.28 (dd,J= 3.0, 1.9 Hz,1H), 5.99 (d,J= 2.7 Hz, 1H), 4.08 (br. s, 2H), 2.67 (t,J= 13.0 Hz, 2H), 2.55(d,J= 7.0 Hz, 2H), 1.77 (ttt,J= 10.9, 7.1, 3.6 Hz, 1H), 1.71 – 1.58 (m, 2H),1.45 (s, 9H), 1.14 (qd,J= 12.5, 4.4 Hz, 2H).13C NMR(101 MHz, CDCl3) δ 154.97,154.34, 141.14, 110.19, 106.22, 79.35, 35.84, 35.00, 32.00, 28.57.IR(neat):2930, 1690, 1421, 1234, 1159, 1009 cm-1。MS(EI): 265 ((M+, 3.06), 57 (100).HRMS(ESI+):m/zcalc’d for (M + Na)+: 288.1570, found 288.1568。
实施例20
本申请实施例提供式1-20所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_47
。
参考实施例1，[Ir(COD)Cl]2(34.2 mg, 0.051 mmol.), L7 (189.3 mg, 0.20mmol.),1-20(303.9 mg, 0.9984 mmol.)，o-Xylene (1.5 mL)，170 °C反应36小时。柱层析（PE/EA = 2/1）得到2-20(131.2 mg, 48%)。1H NMR(400 MHz, CDCl3) δ 8.50 (d,J= 5.7Hz, 2H), 7.07 (d,J= 6.0 Hz, 2H), 4.09 (br. s, 2H), 2.66 (t,J= 12.9 Hz, 2H),2.54 (d,J= 7.2 Hz, 2H), 1.84 – 1.64 (m, 1H), 1.67 – 1.54 (m, 2H), 1.45 (s,9H), 1.16 (qd,J= 12.6, 4.1 Hz, 2H).13C NMR(151 MHz, CDCl3) δ 154.88, 149.78,149.22, 124.63, 79.46, 44.19, 43.64, 42.52, 37.50, 31.96, 28.54.IR(neat):2929, 2854, 1688, 1421, 1160, 1065 cm-1。MS(ESI): 277 ((M + H)+, 33.26), 221(100). HRMS(ESI+):m/zcalc’d for (M + H)+: 277.1911, found 277.1909。
实施例21
本申请实施例提供式1-21所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_48
。
参考实施例1，[Ir(COD)Cl]2(10.3 mg, 0.0153 mmol.), L7 (56.6 mg, 0.0600mmol.),1-21(309.0 mg, 0.9995 mmol.), o-Xylene (1.5 mL).，170 °C反应18小时。柱层析（PE/EA = 10/1）得到2-21(186.2 mg, 66% yield)，淡黄色固体。1H NMR(400 MHz,CDCl3) δ 7.13 (dd,J= 5.1, 1.2 Hz, 1H), 6.92 (dd,J= 5.1, 3.4 Hz, 1H), 6.76(dd,J= 3.4, 1.1 Hz, 1H), 4.07 (br. s, 2H), 2.75 (d,J= 6.7 Hz, 2H), 2.66 (t,J=11.8 Hz, 2H), 1.78 – 1.60 (m, 3H), 1.45 (s, 9H), 1.14 (qd,J= 13.0, 4.0 Hz,2H).13C NMR(101 MHz, CDCl3) δ 154.94, 142.83, 126.85, 125.33, 123.43, 79.36,43.96, 38.70, 36.94, 31.95, 28.57.IR(neat): 2922, 1682, 1424, 1365, 1238,1150 cm-1。MS(ESI): 332 ((M + Na)+, 332 (100). HRMS(ESI+):m/zcalc’d for (M +Na)+: 304.1342, found 304.1339. MP: 33.1-33.9 °C。
实施例22
本申请实施例提供式1-22所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_49
。
参考实施例1，[Ir(COD)Cl]2(17.2 mg, 0.0256 mmol.), L7 (94.2 mg, 0.0999mmol.),1-22(284.2 mg, 0.9992 mmol.)，o-Xylene (1.5 mL)，170 °C反应24小时。柱层析（PE）得到2-22(210.3 mg, 82%)。1H NMR (400 MHz, CDCl3) δ 7.16 (d,J= 8.1 Hz, 1H),6.98 (dd,J= 8.1, 1.6 Hz, 2H), 6.91 – 6.86 (m, 1H), 2.94 – 2.85 (m, 3H), 2.81(hept,J= 6.92 Hz, 1H), 2.25 (dt,J= 12.9, 2.8 Hz, 1H), 2.01 – 1.88 (m, 2H),1.87 – 1.71 (m, 1H), 1.69 (ddd,J= 12.8, 4.7, 2.2 Hz, 1H), 1.64 – 1.43 (m,4H), 1.38 (td,J= 13.1, 3.5 Hz, 1H), 1.22 (d,J= 6.9 Hz, 6H), 1.17 (s, 3H),1.00 (d,J= 7.6 Hz, 3H). 13C NMR(101 MHz, CDCl3) δ 147.31, 145.55, 135.20,127.11, 124.43, 123.93, 44.58, 38.76, 37.42, 34.08, 33.61, 33.23, 30.50,25.70, 24.71, 24.14 (d,J= 2.0 Hz), 18.21, 15.28. MS(EI): 256 (M+, 27.76), 159(100)。
实施例23
本申请实施例提供式1-23所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_50
。
参考实施例1，[Ir(COD)Cl]2(16.6 mg, 0.0247 mmol.), L7 (94.7 mg, 0.1004mmol.),1-23(276.5 mg, 0.4982 mmol.)，o-Xylene (2.0 mL)，170 °C反应36小时。柱层析（PE = 100%）得到2-23(157.9 mg mg, 60% yield)，白色固体。1H NMR(600 MHz, CDCl3) δ5.19 (t,J= 3.7 Hz, 1H), 3.19 (dd,J= 11.3, 4.4 Hz, 1H), 2.34 (dt,J= 13.7, 4.7Hz, 1H), 1.91 – 1.84 (m, 2H), 1.80 (qd,J= 13.2, 3.4 Hz, 1H), 1.70 (tt,J=14.1, 4.7 Hz, 1H), 1.66 – 1.61 (m, 1H), 1.61 – 1.51 (m, 6H), 1.49 – 1.41 (m,3H), 1.42 – 1.30 (m, 3H), 1.29 – 1.17 (m, 3H), 1.11 (s, 3H), 1.10 – 1.05 (m,1H), 1.02 – 0.97 (m, 1H), 0.92 (s, 3H), 0.91 (s, 3H), 0.90 – 0.88 (m, 12H),0.87 (s, 3H), 0.86 (s, 3H), 0.75 (s, 3H), 0.71 (d,J= 1.9 Hz, 1H), 0.03 (s,6H).13C NMR (151 MHz, CDCl3) δ 146.06, 121.32, 79.60, 55.46, 47.90, 45.09,42.56, 41.02, 39.47, 39.26, 38.59, 37.13, 35.85, 33.85, 33.79, 33.27, 31.34,31.21, 28.72, 28.15, 27.80, 26.09, 25.23, 24.01, 23.51, 22.41, 18.75, 18.28,17.61, 16.31, 15.54, -3.57, -4.74. IR(neat): 2926, 2858, 1461, 1386, 1249,1101, 1072, 833 cm-1。HRMS(ESI+):m/zcalc’d for (M + H)+: 527.4643, found527.4644.MP: 204.2-205.2 ℃。
实施例24
本申请实施例提供式1-24所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_51
。
参考实施例1，[Ir(COD)Cl]2(5.1 mg, 0.0076 mmol.), L7 (28.1 mg, 0.0298mmol.),1-24(285.1 mg, 0.5010 mmol.)，,o-Xylene (1.0 mL)，170 °C反应18小时。柱层析（PE = 100%）得到2-24(260.5 mg, 96% yield)，白色固体。1H NMR(400 MHz, CDCl3) δ5.59 (s, 1H), 3.19 (dd,J= 11.5, 4.6 Hz, 1H), 2.73 (dt,J= 13.5, 3.6 Hz, 1H),2.32 (s, 1H), 2.12 – 1.88 (m, 2H), 1.82 (td,J= 13.7, 4.7 Hz, 1H), 1.74 – 1.53(m, 4H), 1.54 – 1.36 (m, 6H), 1.36 (s, 3H), 1.34 – 1.22 (m, 3H), 1.13 (d,J=2.0 Hz, 6H), 1.10 – 0.93 (m, 3H), 0.91 (s, 3H), 0.89 (d,J= 2.7 Hz, 12H), 0.83(s, 3H), 0.77 (s, 3H), 0.67 (d,J= 10.3 Hz, 1H), 0.03 (d,J= 2.3 Hz, 6H).13C NMR(151 MHz, CDCl3) δ 200.62, 170.38, 128.16, 79.42, 62.02, 55.17, 51.82, 45.52,43.44, 41.53, 40.99, 39.86, 39.28, 37.15, 33.51, 33.00, 32.53, 30.77, 28.87,28.64, 27.75, 26.80, 26.76, 26.07, 23.48, 22.53, 18.83, 18.26, 17.84, 16.57,16.24, -3.55, -4.79.IR(neat): 2929, 2857, 1664, 1254, 1208, 1088, 1068, 890,833 cm-1。HRMS(ESI+):m/zcalc’d for (M + H)+: 541.4435, found 541.4430.MP: 244.4– 245.5 °C。
实施例25
本申请实施例提供式1-25所示化合物脱羰氢化的催化方法，具体包括：
Figure SMS_52
。
参考实施例1，[Ir(COD)Cl]2(5.1 mg, 0.0076 mmol.), L7 (28.6 mg, 0.0303mmol.),1-25 (228.4 mg, 0.5023 mmol.)，o-Xylene (1.0 mL)，170 °C反应18小时。柱层析（PE/EA = 10/1）得到2-25(169.1 mg,79%)。1H NMR (400 MHz, CDCl3) δ 5.64 (s, 1H),2.96 (ddd,J= 13.4, 6.8, 4.1 Hz, 1H), 2.63 (ddd,J= 16.9, 11.1, 7.2 Hz, 1H),2.44 (s, 1H), 2.36 (dt,J= 15.7, 5.2 Hz, 1H), 2.12 – 1.98 (m, 2H), 1.85 (td,J=13.6, 4.3 Hz, 1H), 1.79 – 1.64 (m, 1H), 1.64 – 1.50 (m, 4H), 1.52 – 1.38 (m,4H), 1.37 (s, 3H), 1.36 – 1.26 (m, 3H), 1.27 (s, 3H), 1.24 – 1.15 (m, 4H),1.16 – 1.05 (m, 7H), 1.05 – 0.96 (m, 1H), 0.89 (d,J= 6.2 Hz, 3H), 0.85 (s,3H).13C NMR(151 MHz, CDCl3) δ 217.18, 199.58, 170.90, 127.93, 61.07, 55.44,51.80, 47.79, 45.25, 43.50, 41.52, 40.87, 39.82, 36.74, 34.27, 33.41, 32.46,32.18, 30.65, 28.83, 26.74, 26.68, 26.50, 23.33, 22.43, 21.46, 18.88, 18.58,15.74.IR(neat): 2922, 2857, 1720, 1703, 1659, 1343, 1164, 926, 815 cm-1.MS(ESI): 426 ((M + H)+, 426 (100). HRMS(ESI+):m/zcalc’d for (M + H)+: 425.3414,found 425.3413。
对比例1
本申请对比例提供式2-26的制备方法，合成路线如下，具体包括：
Figure SMS_53
。
向2-24(541 mg，1.0 mmol)的5 mL四氢呋喃溶液中加入TBAF (3.0 mL，1.0 M/THF， 3.0 mmol)。在50℃下搅拌24小时。用20 mL饱和NaHCO3水溶液猝灭反应，用20 mL乙酸乙酯萃取3次，用盐水洗涤合并有机层，用Na2SO4干燥，过滤，减压浓缩。通柱层析纯化(PE/EA= 5/1)，得到产物2-26(325 mg，76% yield)，白色固体。1H NMR (400 MHz, CDCl3) δ 5.60(s, 1H), 3.22 (dd,J= 11.0, 5.2 Hz, 1H), 2.78 (d,J= 13.5 Hz, 1H), 2.34 (s,1H), 2.14 – 1.94 (m, 2H), 1.83 (td,J= 13.8, 4.4 Hz, 1H), 1.74 – 1.56 (m, 5H),1.55 – 1.37 (m, 6H), 1.36 (s, 3H), 1.35 – 1.22 (m, 2H), 1.21 – 1.06 (m, 8H),1.04 – 0.92 (m, 5H), 0.88 (d,J= 6.2 Hz, 3H), 0.83 (s, 3H), 0.81 (s, 3H), 0.74– 0.65 (m, 1H).13C NMR(151 MHz, Chloroform-d) δ 200.54, 170.56, 128.07, 78.81,61.88, 55.05, 51.81, 45.48, 43.44, 41.50, 40.94, 39.25, 37.18, 33.47, 32.89,30.73, 28.85, 27.41, 26.75 (d,J= 2.7 Hz), 23.45, 22.51, 18.79, 17.61, 16.49,15.73. MS(ESI): 450 ((M + Na)+, 450 (100)。
实施例26
本申请实施例提供式5-1所示化合物脱羰氢化的催化方法，合成路线如下，具体包括：
Figure SMS_54
。
取一个25 mL史莱克反应管并用高温枪烘干，然后将其移入手套箱，在手套箱中将[Ir(COD)Cl]2(10.2 mg, 0.0152 mmol.), L7 (56.9 mg, 0.0603 mmol.), 上述5-1所示化合物 (303.8 mg, 1.0013 mmol)依次加入该反应管中，最后加入o-Xylene (1.5 mL)。温度升到170 ℃反应24小时后，反应液直接柱层析（PE/EA = 20:1）得到4-1(154.7 mg, 57%yield)，淡黄色油状物。1H NMR (400 MHz, CDCl3) δ 7.33 – 7.24 (m, 2H), 7.24 –7.15 (m, 1H), 7.17 – 7.08 (m, 2H), 4.07 (br. s, 2H), 2.63 (t,J= 12.8 Hz, 2H),2.53 (d,J= 6.9 Hz, 2H), 1.75 – 1.55 (m, 3H), 1.45 (s, 9H), 1.14 (qd,J= 12.5,4.0 Hz, 2H)。
实施例27
本申请实施例提供式3-2所示化合物脱羰氢化的催化方法，合成路线如下，具体包括：
Figure SMS_55
。
参考实施例27，[Ir(COD)Cl]2(10.3 mg, 0.0153 mmol.), L7 (56.7 mg, 0.0601mmol.),上述3-2所示化合物(223.9 mg, 1.0013 mmol.)，o-Xylene (1.5 mL)。170 °C反应24小时。柱层析（PE/EA = 50/1）得到2-15(166.6 mg, 86% yield)。
实施例28
本申请实施例提供式3-3所示化合物脱羰氢化的催化方法，合成路线如下，具体包括：
Figure SMS_56
。
参考实施例27，Ir(COD)Cl]2(10.1 mg, 0.0150 mmol.), L9 (56.5 mg, 0.0599mmol.), aldehyde 上述3-3所示化合物(221.1 mg, 1.0092 mmol.)，o-Xylene (1.5 mL)。170 °C反应24小时。柱层析（PE/EA = 20/1）得到2-17(159.6 mg, 84%)。
实施例29
本申请实施例提供式3-3所示化合物脱羰氢化的催化方法，合成路线如下，具体包括：
Figure SMS_57
。
参考实施例27，[Ir(COD)Cl]2(5.1 mg, 0.0076 mmol.), L7 (28.1 mg, 0.0298mmol.), 上述3-3所示化合物(285.6 mg, 0.5 mmol)，o-Xylene (1.0 mL)。170 °C反应24小时。柱层析（PE/EA = 20/1）得到2-24(239.9 mg, 89%)，白色固体。
测试例
本测试例提供了不同的催化剂配体对α-季醛（式1-1所示化合物）脱羰效率试验，以上述合成路线的式1-1所示化合物为原料，[Ir(COD)Cl2]为金属催化剂，筛选不同的催化剂配体骨架，合成路线如下：
Figure SMS_58
。
1、测定不同催化剂配体对α-季醛（式1-1所示化合物）脱羰的转化率和收率（收率通过NMR计算），其中，催化剂配体上载量为12 mol%，结果如图2和表1所示。
从图2和表1所示，不同催化剂配体对大位阻α-季醛的脱羰产率有着明显的差别。单齿配体考察了Ph3P, Cy3P, CyJohnphos, JohnPhos, 除了Ph3P有3%的产物生成，其他几个单齿配体均没有催化效果。紧接着测试了双齿配体，本测试例首先筛选了商业可得价格低廉的直链型双齿配体DPPE, DPPP, DPPB, DPPPe, DPPH, 实验结果显示使用DPPE配体可以得到28%产物，而其他几个配体催化效果较差或者几乎没有效果。接下来，本测试例测试了其他不同骨架双齿配体：2,2'-双(二苯基磷)联苯、1,2-双(二苯基膦基)苯、1,8-双(二苯基膦)萘、 4,5-双二苯基膦-9,9-二甲基氧杂蒽(XantPhos)，通过实验结果，本测试例发现联苯型配体2,2'-双(二苯基磷)联苯可以得到44%的收率，而其他几个配体催化效果远远低于联苯配体。由于联苯型配体展现出明显的优势，所以本测试例接下来又测试了其他几种联苯型配体：(6,6'-二甲氧基联苯-2,2'-基)双(二苯基膦)（MeO-BIPHEP）、5,5'-双(二苯基磷)-4,4'-二-1,3-苯并二氧(SEGPHOS)、6,6'-双(二苯基磷)-2,2',3,3'-四氢-5,5'-二-1,4-苯并二辛烷（SYNPHOS）以及1,1'-联萘-2,2'-双二苯膦 (BINAP)，通过实验结果，本测试例可以看出MeO-BIPHEP，SEGPHOS与SYNPHOS三个配体催化脱羰得到产物的收率分别为65%，64%和62%，这三个配体的催化效果优于BINAP的54%；而MeO-BIPHEP的催化效果要比SEGPHOS与SYNPHOS有微弱的优势，所以本测试例选择MeO-BIPHEP作为骨架，对该类型配体继续优化反应条件。
3、选择MeO-BIPHEP作为骨架，上述合成路线中式1-1所示化合物为α-季碳醛，该MeO-BIPHEP配体L如表1所示。对该类型配体继续优化反应条件。
反应条件：反应在25mL Schlenk管中进行，在170°C下，用本测试例的式1-1所示化合物（1.0 mmol）、[Ir(COD)Cl]2（0.015 mmol）配体（0.06 mmol）和邻二甲苯（1.5 mL）在18h内进行，产率通过以均三甲苯为内标物的粗反应混合物的NMR分析确定。b.单独产量。c.150 mg 3ÅMS。D. 10 mol%P/C负载[Ir(COD)Cl]2。E. 50 mol%P/C负载[Ir(COD)Cl]2。
其中，表1中配体催化剂L的结构式如下：
Figure SMS_59
。
表1不同的配体脱羰产率的结果
Figure SMS_60
从表1可知，基于MeO-BIPHEP类型配体，考察了不同配体L2到L10，本测试例发现配体L7的催化效率最高，核磁收率90%，分离收率可以得到83%。同时本测试例也考察了醛脱羰经典催化体系Rh/dppp与Rh(Ph3P)3Cl，在大位阻醛脱羰中Rh(Ph3P)3Cl催化活性较低，核磁收率仅为6%，而Rh/dppp体系则完全没有催化活性。另外本测试例还考察了Pd/C的催化体系，实验结果表明，即使将Pd/C的催化剂上载量升到50 mol%, 脱羰产物只有32%，而原料则基本分解完全。此催化体系在大位阻醛的脱羰效率上远远低于本申请的催化体系金属铱-BIPHEP体系。最后通过对照实验得知，金属铱与配体缺一不可，二者结合才有催化活性。
4、按照以下合成路线的条件，测定不同α-季碳醛的脱羰氢化的选择范围，不同α-季碳醛脱羰氢化后得到的醛基α位手性碳构型保持产物结构式如图3~图4所示，通过以下合成路线测定不同α-季碳醛脱羰氢化得到对应醛基α位手性碳构型保持产物的产率，产率结果如图3~图4所示。
Figure SMS_61
。
反应条件：上述式1的α-季碳醛 (1.0 mmol), [Ir(COD)Cl]2(0.015 mmol)，L7(0.06 mmol), o-Xylene (1.5 mL), 170 ℃, 18 h. 分离收率。 b 24 h. c 36 h. d [Ir(COD)Cl] (0.025 mmol), L7 (0.1 mmol). e [Ir(COD)Cl] (0.05 mmol), L7 (0.2 mmol). f o-Xylene (1.0 mL). g o-Xylene (2.0 mL). h 1(0.5 mmol). i 核磁收率。
不同α-季碳醛中，哌啶环氮原子的不同保护基如Ts, Cbz, Bz均可以得到90%以上的脱羰产物；底物中含有甲基、氮、氧、氟与酯基等基团兼容性良好；对于无杂原子的环状醛同样可以得到比较高的收率；五元环与四元环以及含有刚性环的大位阻醛在该催化体系下同样可以较高收率脱羰；除了环状醛，链状α-季醛也表现出较高的催化效率；对于杂环噻吩，吡啶，呋喃都可以兼容。另外值得注意的是，对于天然产物松香酸、甘草次酸、齐墩果酸衍生的α-手性季醛脱羰后醛基邻位的手性碳原子构型保持。进一步通过对2-26单晶衍射确定了脱羰后构型保持。本测试例测到化合物1-25未被保护的羟基在Ir-L7催化下生成一个含有酮羰基结构的化合物2-25，说明此催化体系不仅可以脱羰还可以对一级醇和二级醇脱氢生成相应的醛和酮，基于此结果，本测试例说明本申请提供的催化体系可以对伯醇进行脱氢生成醛，然后继续对醛进行脱羰。
5、按照以下合成路线的条件，测定不同α-季碳醛的脱羰氢化的选择范围。
Figure SMS_62
。
合成图5中式2-1所示化合物、式2-15所示化合物、式2-17所示化合物的反应条件：上述式3所示化合物的α-季碳醛 (1.0 mmol), [Ir(COD)Cl]2(0.015 mmol)，L7 (0.06mmol),o-Xylene (1.5 mL), 170 ℃反应 24 h。
合成图5中式2-24所示化合物的反应条件：上述式3所示化合物的α-季碳醛 (0.5mmol), [Ir(COD)Cl]2(0.0075 mmol)，L7 (0.03 mmol),o-Xylene (1.0 mL), 170 ℃反应24 h。实验结果表明，伯醇的脱氢脱羰在Ir-L7催化体系下可以顺利进行，对于手性的底物（上述式3-3所示化合物的α-季碳醛）可以顺利脱氢脱羰得到2-24，同样对于羟基β位手性碳构型保持。
对比例2
本申请对比例提供了采用不同催化剂配体催化α-季碳醛脱羰氢化的试验，具体包括：
按照以下合成路线，采用表2中催化剂配体L对α-季碳醛进行脱羰氢化。
Figure SMS_63
。
表2 不同的配体脱羰产率的结果
Figure SMS_64
对比例3
本申请本申请对比例提供了采用不同催化剂配体催化α-季碳醛脱羰氢化的试验，具体包括：
按照以下合成路线，采用图6提供的催化剂配体L对α-季碳醛进行脱羰氢化，不同催化剂配体催化α-季碳醛脱羰氢化的转化率和产率如图6所示。
Figure SMS_65
。
对比例4
本申请本申请对比例提供了采用不同催化剂配体催化不同α-季碳醛脱羰氢化的试验，具体包括：
按照以下合成路线，采用表3提供的α-季碳醛M和催化剂配体L对进行脱羰氢化试验，不同催化剂配体催化不同α-季碳醛脱羰氢化的转化率和产率结果如表3所示。
Figure SMS_66
。
表3 不同的配体脱羰产率的结果
Figure SMS_67
表3中“-”为不添加催化剂配体。
从表2~表3和图6数据可知，采用非BIPHEP配体或者采用非金属铱组成的催化剂体系无法催化α-季碳醛脱羰氢化，可见，本申请的催化剂体系中金属铱与配体缺一不可，二者结合才有催化催化α-季碳醛脱羰氢化的活性。
以上所述仅是本申请的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本申请原理的前提下，还可以作出若干改进和润饰，这些改进和润饰也应视为本申请的保护范围。

Claims (9)

1.一种催化α-季碳醛脱羰氢化的方法，其特征在于，所述催化α-季碳醛脱羰氢化的催化剂体系由金属铱和BIPHEP配体组成；
所述金属铱为[Ir(COD)Cl]2或/和[Ir(COE)Cl]2；
所述BIPHEP配体选自(6,6'-二甲氧基联苯-2,2'-基)双(二苯基膦)、(6,6′-二甲氧基联苯-2,2′-二基)二[双(4-甲氧基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二甲氧基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二甲基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二叔丁基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二苯基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,5-二三氟甲基苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,4,5-三氟苯基)膦]、(6,6′-二甲氧基联苯-2,2′-二基)二[双(3,4,5-三甲氧基苯基)膦]、(6,6'-二甲氧基联苯-2,2'-基)双(二异丙基膦)、1,1'-联萘-2,2'-双二苯膦、5,5'-双(二苯基磷)-4,4'-二-1,3-苯并二氧和[(5,6),(5',6')-双(乙烯二氧)联苯-2,2'-基]二苯基磷中的一种或多种；
所述α-季碳醛具有式I所示结构；
Figure QLYQS_1
式I；
其中，R1、R2和R3各自独立地为取代或非取代烷基、取代或非取代环烷烃、取代或非取代杂环烷烃。
2.根据权利要求1所述的方法，其特征在于，所述金属铱原子和所述BIPHEP配体的摩尔比为1 : (0.5~3)。
3.根据权利要求1所述的方法，其特征在于，所述α-季碳醛为通过式II原位脱除一分子的氢气产生如所述式I中的醛基；
Figure QLYQS_2
式II；
其中，R1、R2和R3各自独立地为取代或非取代烷基、取代或非取代环烷烃、取代或非取代杂环烷烃。
4.根据权利要求1所述的方法，其特征在于，所述R1、所述R2和所述R3各自独立地选自卤素、C1～12烷基、C1～12卤代烷基、C1～12芳基取代烷基、C1～12氨基取代烷基、C1～12烷氧基取代烷基、C1～12吡啶取代烷基、C1～12噻吩取代烷基、C1～12呋喃取代烷基、C3～12环烷基、C3～12氨基取代环烷基、C12～18稠和环；其中的杂原子为N和O卤素中的一种或多种，一个或多个。
5.根据权利要求4所述的方法，其特征在于，所述α-季碳醛选自：
Figure QLYQS_4
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Figure QLYQS_5
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Figure QLYQS_8
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Figure QLYQS_9
、
Figure QLYQS_11
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Figure QLYQS_14
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Figure QLYQS_16
、
Figure QLYQS_19
、/>
Figure QLYQS_20
、/>
Figure QLYQS_21
、/>
Figure QLYQS_22
、
Figure QLYQS_23
、/>
Figure QLYQS_24
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Figure QLYQS_25
、/>
Figure QLYQS_26
、
Figure QLYQS_3
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Figure QLYQS_6
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Figure QLYQS_7
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Figure QLYQS_10
、
Figure QLYQS_12
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Figure QLYQS_13
、/>
Figure QLYQS_15
、
Figure QLYQS_17
和/>
Figure QLYQS_18
中的一种或多种。
6.一种催化α-季碳醛脱羰氢化的方法，其特征在于，包括以下步骤：
将α-季碳醛与溶剂混合，在催化剂存在的条件下进行加热反应，得到与所述α-季碳醛对应的醛基α位由季碳转化成一个次甲基且其手性碳构型保持的产物；所述催化剂为权利要求1或2所述的方法中的催化剂体系；所述α-季碳醛为权利要求3~5任意一项所述的方法中的α-季碳醛。
7.根据权利要求6所述的方法，其特征在于，所述α-季碳醛、所述金属铱与所述BIPHEP配体的摩尔比为100:(0.1~10):(0.05~30)。
8.根据权利要求6所述的方法，其特征在于，所述溶剂选自邻二甲苯、间二甲苯、对二甲苯、混合二甲苯、异丙苯、乙苯、叔丁基苯、伞花烃和二乙二醇二甲醚中的一种或多种。
9.根据权利要求6所述的方法，其特征在于，所述加热反应的温度为130 ~ 190 ℃，所述加热反应的时间为5 ~ 30小时。
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