CN113087691B - 一种基于动力学拆分策略合成手性芳基叔醇和苯并吡喃类化合物的方法 - Google Patents
一种基于动力学拆分策略合成手性芳基叔醇和苯并吡喃类化合物的方法 Download PDFInfo
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- CN113087691B CN113087691B CN202110326054.7A CN202110326054A CN113087691B CN 113087691 B CN113087691 B CN 113087691B CN 202110326054 A CN202110326054 A CN 202110326054A CN 113087691 B CN113087691 B CN 113087691B
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- chiral
- tertiary alcohol
- cdcl
- nmr
- benzopyran
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- 238000000034 method Methods 0.000 title claims abstract description 62
- -1 aryl tertiary alcohol Chemical class 0.000 title claims abstract description 55
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 7
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 claims abstract description 71
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 28
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 14
- 239000003513 alkali Substances 0.000 claims abstract description 6
- 150000001503 aryl iodides Chemical class 0.000 claims abstract description 6
- 150000001562 benzopyrans Chemical class 0.000 claims abstract description 6
- 239000003054 catalyst Substances 0.000 claims abstract description 6
- 239000003446 ligand Substances 0.000 claims abstract description 6
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 5
- 230000009471 action Effects 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims abstract description 3
- 125000003518 norbornenyl group Chemical class C12(C=CC(CC1)C2)* 0.000 claims abstract 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 82
- 230000035484 reaction time Effects 0.000 claims description 34
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical class CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
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- 125000000217 alkyl group Chemical group 0.000 claims description 5
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- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
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- 125000003118 aryl group Chemical group 0.000 claims description 4
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- 239000000376 reactant Substances 0.000 claims description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- KRZJRNZICWNMOA-GXSJLCMTSA-N (3s,4r)-4,8-dihydroxy-3-methoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound C1=CC=C2[C@@H](O)[C@@H](OC)CC(=O)C2=C1O KRZJRNZICWNMOA-GXSJLCMTSA-N 0.000 claims description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 claims description 2
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- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
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- 101150003085 Pdcl gene Proteins 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 2
- 239000012298 atmosphere Substances 0.000 claims description 2
- DLIJPAHLBJIQHE-UHFFFAOYSA-N butylphosphane Chemical compound CCCCP DLIJPAHLBJIQHE-UHFFFAOYSA-N 0.000 claims description 2
- ZOAIGCHJWKDIPJ-UHFFFAOYSA-M caesium acetate Chemical compound [Cs+].CC([O-])=O ZOAIGCHJWKDIPJ-UHFFFAOYSA-M 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims description 2
- 229910052808 lithium carbonate Inorganic materials 0.000 claims description 2
- 235000011056 potassium acetate Nutrition 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- WFIZEGIEIOHZCP-UHFFFAOYSA-M potassium formate Chemical compound [K+].[O-]C=O WFIZEGIEIOHZCP-UHFFFAOYSA-M 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
- 230000001681 protective effect Effects 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
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Abstract
本发明公开了一种基于动力学拆分策略合成手性芳基叔醇和苯并吡喃类化合物的方法。该方法以简单的芳基碘化物和消旋的芳基叔醇为起始原料，在钯催化剂、膦配体、手性降冰片烯衍生物以及碱的作用下，在50‑130℃下于有机溶剂中搅拌反应，即可得到手性芳基叔醇和苯并吡喃类化合物。该方法具有原料廉价易得，制备过程简单，动力学拆分效果好，选择性因子高，对映选择性优异，底物适用范围广等优点。本发明方法对消旋的叔醇底物进行动力学拆分后能以优秀的收率和对映选择性得到手性苯并吡喃产物和回收手性叔醇原料，选择性因子高达544，是现有不对称催化策略的重要补充，具有较高的应用价值。
Description
技术领域
本发明属于有机合成领域，涉及一种基于动力学拆分策略合成手性芳基叔醇和苯并吡喃类化合物的方法。
背景技术
手性芳基叔醇是一类非常重要的结构单元，广泛存在于药物分子中。如非阿片类中枢性镇痛药盐酸曲马多((-)-tramadol hydrochloride)，抗真菌剂艾氟康唑(efinaconazole)、伏立康唑(voriconazole)，抗组胺药富马酸氯马斯汀(clemastinefumarate)，抗艾滋病药依法韦仑(efavirenz)和强镇痛药阿法罗定(alphaprodine)等。因此，探索该类结构单元的高效不对称合成方法具有十分重要的意义。
动力学拆分是获取手性醇化合物最有效、最实用的方法之一。迄今为止，已经有很多方法实现了仲醇化合物的动力学拆分，然而对于难度更大的叔醇化合物的高效动力学拆分的研究则相对较少，主要原因是叔醇化合物由于其空间位阻较大导致其反应活性较低；另外，要精准识别醇羟基所在碳上的三个非氢取代基也是非常困难的。目前已实现的叔醇化合物的动力学拆分方法包括路易斯碱催化的酰化反应([1]J.Org.Chem.2001,66,5522；[2]Angew.Chem.Int.Ed.2013,52,1731；[3]Angew.Chem.Int.Ed.2018,57,3200；[4]Angew.Chem.Int.Ed.2020,59,16572；[5]Org.Lett.2021,23,1169)，布朗斯特酸催化的(转)缩醛化、转酯化、缩合反应([6]J.Am.Chem.Soc.2015,137,1778；[7]Angew.Chem.Int.Ed.2019,58,10315；[8]Angew.Chem.Int.Ed.2020,59,2333；[9]Adv.Synth.Catal.2021,363,200)，过渡金属催化的逆烯丙基化、羧基化、硅基化、环加成反应等([10]Org.Lett.2008,10,1191；[11]Chem.Commun.2018,54,6064；[12]Angew.Chem.Int.Ed.2019,58,1970；[13]Angew.Chem.Int.Ed.2021,doi:10.1002/anie.202016286)。尽管叔醇的动力学拆分已经取得了一定的发展，但在动力学拆分效率、底物普适性等方面仍有很大的改进空间。因此发展更加高效的利用简单易得的拆分试剂实现叔醇动力学拆分的新方法，具有非常重要的研究意义。
发明内容
为了解决现有技术中存在的不足，本发明提供一种基于动力学拆分策略合成手性芳基叔醇和苯并吡喃类化合物的方法。该方法具有原料廉价易得，制备过程简单，动力学拆分效果好，选择性因子高，对映选择性优异，底物适用范围广等优点。
本发明提供的技术方案具体如下：
一种基于动力学拆分策略合成手性芳基叔醇和苯并吡喃类化合物的方法，包括以下步骤：
在保护气体氛围下，以消旋的芳基叔醇A和芳基碘化物B为起始原料，在钯催化剂C、膦配体D、手性降冰片烯衍生物E和碱F的作用下，于有机溶剂G中搅拌反应完全，反应结束后分离反应物即可得到手性芳基叔醇和苯并吡喃类化合物；
反应方程式如下：
其中，R1-R4为芳基、杂环芳基、烷基、酯基、醛基、羧基、羟基、巯基、硅基、氨基、氰基、硝基、酰胺基、磺酰基、烷氧基、烯基、炔基、卤素中的一种或几种；x表示R1的个数，0≤x≤4；y表示R4的个数，0≤y≤4；Ar1和Ar2为芳烃或杂环芳烃。优选的，烷基为具有1～20个碳原子的烷基，例如甲基、乙基、异丙基、癸基、十六烷基等；烷氧基是指具有1～10个碳原子的烷氧基，例如甲氧基等；卤素是指氟、氯、溴、碘。
进一步，所述保护气体选自氩气、氮气中的一种。优选为氩气。
进一步，所述钯催化剂C为Pd(PPh3)4、Pd(dba)2、Pd2(dba)3、Pd(OAc)2、Pd(PhCN)2Cl2、Pd(MeCN)2Cl2、PdCl2、PdI2、[Pd(allyl)Cl]2中的任意一种或几种。优选Pd(OAc)2。
进一步，所述的碱F为碳酸锂、碳酸钠、碳酸钾、碳酸铯、醋酸钠、醋酸钾、醋酸铯、磷酸三钾、甲酸钾、碳酸氢钠、碳酸氢钾、氢氧化钠、氢氧化钾、叔丁醇钠、叔丁醇钾中的任意一种或几种。优选碳酸钾。
进一步，所述的有机溶剂G为甲醇、乙醇、异丙醇、叔丁醇、四氢呋喃、2-甲基四氢呋喃、乙醚、二甲基乙二醚、甲基叔丁基醚、1,4-二氧六烷、1,3-二氧六烷、二氯甲烷、1,2-二氯乙烷、氯仿、四氯化碳、C4-12的饱和烷烃、C3-12的氟代或者氯代烷烃、苯、甲苯、二甲苯、三甲苯、二甲亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、丙酮、N-甲基吡咯烷酮、乙腈、C3-12的饱和烷基腈中的任意一种或几种。优选甲苯。
进一步，所述的膦配体D为三芳基膦、三烷基膦、二环己基(2',4',6'-三异丙基-[1,1'-二苯基]-2-基)膦、二环己基(2',4',6'-三异丙基-3,6-二甲氧基-[1,1'-二苯基]-2-基)膦、二环己基(2',6'-二甲氧基-[1,1'-二苯基]-2-基)膦、2'-(二环己基膦基)-N,N-二甲基-[1,1'-二苯基]-2-胺、二环己基(2',6'-二异丙氧基-[1,1'-二苯基]-2-基)膦、三(2-呋喃基)膦、(3S,5S,7S)-金刚烷-1-基((1R,5S)-金刚烷-2-基)(丁基)膦中的任意一种或几种。优选三(2-呋喃基)膦。
进一步，所述手性降冰片烯衍生物E的结构式为：
其中：
i)R5为左边五元环上的取代基，p代表取代基个数，0≤p≤8；R6为双键上的取代基，q代表取代基个数，0≤q≤2；
ii)左边五元环上取代基数目为2个及2个以上时，可以相同，也可以不相同；双键上的取代基数目为2个时，可以相同，也可以不相同；
iii)R5和R6取代基的种类可以相同，也可以不相同；
iii)每个R5和R6独立地为酯基、羧基、氰基、硝基、酰胺基、磺酰基、羟基、巯基、烷氧基、芳基、杂环芳基、烷基和卤素等。优选(1S,4R)-2-降冰片烯甲酯作为手性共催化剂。
进一步，所述反应温度为50-130℃，反应时间为5-72h。加热过程可采用油浴(如硅油、石蜡油等)或者其它加热方式。优选反应温度105℃。
进一步，所述分离反应物的方法为：将反应混合物过滤、浓缩和柱层析纯化。所述过滤采用抽滤，抽滤过程可使用砂芯漏斗在减压的条件下过滤。所述浓缩过程可采用减压蒸馏等方法，例如用旋转蒸发仪减压浓缩。所述纯化方法可采用柱层析分离纯化。
进一步，各原料的投料摩尔比为芳基叔醇A:芳基碘化物B:催化剂C:膦配体D:降冰片烯衍生物E:碱F＝2.0:1.6:0.05:0.2:0.6:2.4。
本发明的方法可以高效地制备手性芳基叔醇和苯并吡喃化合物，和现有技术相比，本发明具有以下有益效果：
i)本发明所涉及的主要原料芳基碘化物绝大部分为商品化试剂，且价格低廉，种类繁多；另一反应组分芳基叔醇制备简单，只需几步转化即可得到；
ii)本发明方法的动力学拆分效果好，反应对消旋的叔醇底物进行动力学拆分后能以优秀的收率和对映选择性得到手性苯并吡喃产物和回收手性叔醇原料，选择性因子高达544；
iii)本发明方法仅需简单的手性降冰片烯衍生物作为手性源即可实现高效的动力学拆分，是现有不对称催化策略的重要补充，具有较高的应用价值；
iv)本发明方法具有很好的底物适用范围和官能团兼容性。
具体实施方式
下面通过实例对本发明给予进一步说明，值得注意的是，本发明不仅限于下述实施例。
实施例1：手性苯并吡喃3a和手性叔醇1a的制备
在氩气保护下，向干燥并装有磁力搅拌子的反应管中加入醋酸钯(1.1mg，0.005mmol)、三(2-呋喃基)膦(4.6mg，0.02mmol)、碳酸钾(33.2mg,0.24mmol)和干燥的甲苯(1.0mL)，然后加入(1S,4R)-2-降冰片烯-2-甲酸甲酯(N1*)(9.1mg，0.06mmol)、1-碘萘(2a)(40.6mg，0.16mmol)和消旋的芳基叔醇(1a)(58.2mg，0.2mmol)。所得混合物于105℃在氩气保护氛围下反应24小时。反应结束后冷却至室温，混合物用硅藻土过滤，乙酸乙酯洗涤，减压蒸馏除去溶剂，柱层析分离纯化得手性苯并吡喃产物(S)-3a和回收未反应的手性叔醇(R)-1a。手性苯并吡喃产物(S)-3a：无色油状液体，46％产率，94％ee。1H NMR(400MHz,CDCl3):δ8.51(d,J＝8.4Hz,1H),7.80(d,J＝8.8Hz,1H),7.76(d,J＝7.5Hz,1H),7.58–7.45(m,2H),7.40(d,J＝8.7Hz,1H),7.35–7.26(m,5H),7.13–7.02(m,3H),2.72(s,3H),2.15(s,3H)；13C NMR(100MHz,CDCl3):δ150.02,144.80,139.80,134.19,133.70,132.20,129.71,127.80,127.45,127.36,126.96,126.54,126.18,126.09,125.66,125.19,123.47,122.49,119.90,119.21,82.61,29.03,23.69；HRMS(ESI-TOF):calc’d for C25H21O[M+H+]337.1587,found 337.1579；HPLC:Chiralpak OD column,hexane:isopropanol＝98:2,1mL/min,254nm；tR＝4.68min(minor),5.41min(major)；[α]D 25＝160.6(c＝1.0,CHCl3).手性叔醇 (R)-1a：无色油状液体，42％回收率，96％ee。1H NMR(400MHz,CDCl3):δ7.64(dd,J＝7.7,1.7Hz,1H),7.33–7.22(m,7H),3.77(s,1H),2.37(s,3H),1.95(s,3H)；13C NMR(100MHz,CDCl3):δ148.44,145.18,140.16,130.51,128.28,128.24,126.99,126.80,126.39,125.52,78.10,31.30,24.44；HRMS(ESI-TOF):calc’d for C15H15BrNaO[M+Na+]313.0198,found 313.0189；HPLC:Chiralpak OD column,hexane:isopropanol＝98:2,1mL/min,220nm；tR＝7.70min(minor),8.82min(major)；[α]D 25＝52.5(c＝1.0,CHCl3).
实施例2：手性苯并吡喃3b的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-甲基碘苯(34.9mg)，得手性苯并吡喃产物(S)-3b：无色油状液体，42％产率，94％ee。1H NMR(400MHz,CDCl3):δ7.43(dd,J＝8.0,1.5Hz,1H),7.26–7.17(m,5H),7.16–7.06(m,3H),6.97(d,J＝7.4Hz,1H),6.78(t,J＝7.7Hz,1H),2.61(s,3H),2.34(s,3H),2.00(s,3H)；13C NMR(100MHz,CDCl3):δ152.53,144.92,140.31,134.55,132.01,130.04,129.71,127.81,127.34,126.86,126.78,126.41,125.53,124.00,123.32,120.23,81.86,28.92,23.72,16.28；HRMS(ESI-TOF):calc’d forC22H21O[M+H+]301.1587,found 301.1577；HPLC:Chiralpak OD column,hexane,1mL/min,220nm；tR＝13.92min(major),17.82min(minor)；[α]D 25＝-31.8(c＝1.0,CHCl3).
实施例3：手性苯并吡喃3c的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-乙基碘苯(37.1mg)，反应时间为10小时，得手性苯并吡喃产物(S)-3c：无色油状液体，44％产率，93％ee。1H NMR(400MHz,CDCl3):δ7.52(dd,J＝7.9,1.5Hz,1H),7.34–7.27(m,4H),7.25–7.15(m,4H),7.09(dd,J＝7.5,1.4Hz,1H),6.91(t,J＝7.7Hz,1H),3.00–2.91(m,1H),2.79–2.72(m,1H),2.69(s,3H),2.05(s,3H),1.30(t,J＝7.5Hz,3H)；13C NMR(100MHz,CDCl3):δ151.97,144.87,140.55,134.49,132.93,131.98,129.73,128.27,127.82,127.37,126.84,126.62,125.51,123.97,123.31,120.37,81.78,28.43,23.74,22.97,14.47；HRMS(ESI-TOF):calc’d for C23H23O[M+H+]315.1743,found 315.1739；HPLC:Chiralpak OD column,hexane,1mL/min,220nm；tR＝10.92min(major),14.17min(minor)；[α]D 25＝1.0(c＝1.0,CHCl3).
实施例4：手性苯并吡喃3d的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-异丙基碘苯(39.4mg)，反应时间为21小时，得手性苯并吡喃产物(S)-3d：无色油状液体，41％产率，92％ee。1H NMR(400MHz,CDCl3):δ7.47(dd,J＝7.9,1.5Hz,1H),7.32–7.24(m,3H),7.27–7.07(m,6H),6.90(t,J＝7.7Hz,1H),3.67–3.57(m,1H),2.66(s,3H),2.01(s,3H),1.27(d,J＝7.0Hz,3H),1.22(d,J＝6.9Hz,3H)；13C NMR(100MHz,CDCl3):δ150.96,144.63,140.59,137.47,134.38,131.83,129.75,127.68,127.30,126.68,125.39,125.18,123.88,123.15,120.43,81.67,28.05,26.11,24.02,23.59,22.55；HRMS(ESI-TOF):calc’d for C24H25O[M+H+]329.1900,found 329.1895；HPLC:Chiralpak OD column,hexane,1mL/min,230nm；tR＝7.39min(major),9.60min(minor)；[α]D 25＝1.1(c＝1.0,CHCl3).
实施例5：手性苯并吡喃3e的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-三氟甲基碘苯(43.5mg)，反应时间为21小时，得手性苯并吡喃产物(S)-3e：白色固体，38％产率，87％ee。1H NMR(400MHz,CDCl3):δ7.79(dd,J＝8.0,1.5Hz,1H),7.42(dd,J＝8.0,1.4Hz,1H),7.32–7.24(m,4H),7.22–7.11(m,4H),7.00–6.92(m,1H),2.63(s,3H),2.07(s,3H)；13C NMR(100MHz,CDCl3):δ152.63,143.75,140.04,134.54,132.33,131.21,128.12,127.86,127.71,127.01,125.95(q,J＝5.1Hz),125.62,123.84(q,J＝272.0Hz),123.47,119.93,119.45,82.97,28.25,23.61；19F NMR(376MHz,CDCl3):δ-61.18；HRMS(ESI-TOF):calc’d for C22H18F3O[M+H+]355.1304,found 355.1295；HPLC:Chiralpak IA column,hexane,1mL/min,254nm；tR＝6.14min(major),6.65min(minor)；[α]D 25＝-30.2(c＝1.0,CHCl3).
实施例6：手性苯并吡喃3f的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-氟碘苯(35.5mg)，反应时间为48小时，得手性苯并吡喃产物(S)-3f：白色固体，51％产率，94％ee。1H NMR(400MHz,CDCl3):δ7.29(dt,J＝7.9,1.3Hz,1H),7.26–7.16(m,5H),7.11–7.01(m,3H),6.89–6.84(m,1H),6.77–6.72(m,1H),2.56(s,3H),2.00(s,3H)；13C NMR(100MHz,CDCl3):δ152.87(d,J＝244.2Hz),144.16,142.51,142.40,140.22,134.84,132.27,128.67(d,J＝3.3Hz),127.99,127.54,127.18,126.20,123.66,122.99(d,J＝3.5Hz),120.72(d,J＝7.2Hz),115.16(d,J＝18.1Hz),82.80,29.49,23.62；19F NMR(376MHz,CDCl3):δ-135.92；HRMS(ESI-TOF):calc’d for C21H18FO[M+H+]305.1336,found 305.1329；HPLC:Chiralpak IA column,hexane,1mL/min,254nm；tR＝6.89min(major),8.07min(minor)；[α]D 25＝-74.0(c＝1.0,CHCl3).
实施例7：手性苯并吡喃3g的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-甲基-3-氯碘苯(40.4mg)，反应时间为18小时，得手性苯并吡喃产物(S)-3g：无色油状液体，46％产率，89％ee。1H NMR(400MHz,CDCl3):δ7.37(d,J＝8.6Hz,1H),7.28(d,J＝4.7Hz,2H),7.23(d,J＝11.7Hz,1H),7.20–7.12(m,5H),6.91(d,J＝8.5Hz,1H),2.60(s,3H),2.42(s,3H),2.03(s,3H)；13C NMR(100MHz,CDCl3):δ153.25,144.38,139.84,134.47,134.08,132.13,129.18,127.93,127.53,127.17,126.36,125.60,125.42,123.39,122.72,121.21,82.56,28.94,23.62,13.10；HRMS(ESI-TOF):calc’d for C22H20ClO[M+H+]335.1197,found 335.1189；HPLC:Chiralpak IA column,hexane,1mL/min,320nm；tR＝5.93min(major),7.30min(minor)；[α]D 25＝19.2(c＝1.0,CHCl3).
实施例8：手性苯并吡喃3h的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-甲基-3-氟碘苯(37.8mg)，反应时间为12小时，得手性苯并吡喃产物(S)-3h：无色油状液体，45％产率，93％ee。1H NMR(400MHz,CDCl3):δ7.41(dd,J＝8.8,6.3Hz,1H),7.29–7.27(m,2H),7.25–7.11(m,6H),6.63–6.58(m,1H),2.62(s,3H),2.29(s,3H),2.04(s,3H)；13C NMR(100MHz,CDCl3):δ160.97(d,J＝244.9Hz),153.78(d,J＝8.5Hz),144.53,139.43,134.16,132.13,129.36,127.90,127.50,126.80,126.35,125.58(d,J＝10.1Hz),123.40,120.31(d,J＝3.5Hz),114.30(d,J＝19.0Hz),107.42(d,J＝22.6Hz),82.53,28.94,23.70,8.20(d,J＝4.1Hz)；19F NMR(376MHz,CDCl3):δ-116.05；HRMS(ESI-TOF):calc’d for C22H20FO[M+H+]319.1493,found319.1485；HPLC:Chiralpak IA column,hexane,1mL/min,254nm；tR＝5.92min(major),6.99min(minor)；[α]D 25＝-27.2(c＝1.0,CHCl3).
实施例9：手性苯并吡喃3i的制备
操作步骤同实施例1，区别在于所使用的碘化物为2,3-二甲基碘苯(37.1mg)，反应时间为24小时，得手性苯并吡喃产物(S)-3i：无色油状液体，40％产率，93％ee。1H NMR(400MHz,CDCl3):δ7.35(d,J＝8.0Hz,1H),7.27–7.18(m,5H),7.18–7.08(m,3H),6.71(d,J＝8.0Hz,1H),2.63(s,3H),2.30(s,3H),2.23(s,3H),2.01(s,3H)；13C NMR(100MHz,CDCl3):δ152.20,145.05,139.99,137.44,134.29,131.90,130.02,127.79,127.26,126.47,126.44,125.29,124.71,123.29,121.96,121.73,81.88,29.01,23.72,20.14,12.06；HRMS(ESI-TOF):calc’d for C23H23O[M+H+]315.1743,found 315.1737；HPLC:Chiralpak IAcolumn,hexane,1mL/min,220nm；tR＝6.36min(major),8.14min(minor)；[α]D 25＝-7.6(c＝1.0,CHCl3).
实施例10：手性苯并吡喃3j的制备
操作步骤同实施例1，区别在于所使用的碘化物为2,4-二甲基碘苯(37.1mg)，反应时间为29小时，得手性苯并吡喃产物(S)-3j：无色油状液体，38％产率，95％ee。1H NMR(400MHz,CDCl3):δ7.26–7.07(m,9H),6.81(d,J＝2.0Hz,1H),2.64(s,3H),2.33(s,3H),2.21(s,3H),2.01(s,3H)；13C NMR(100MHz,CDCl3):δ150.28,145.13,140.35,134.49,131.95,130.84,129.84,129.05,127.79,127.25,126.70,126.41,126.28,125.97,123.71,123.35,81.69,29.05,23.76,21.25,16.20；HRMS(ESI-TOF):calc’d for C23H23O[M+H+]315.1743,found 315.1735；HPLC:Chiralpak IA column,hexane,1mL/min,254nm；tR＝5.29min(major),6.65min(minor)；[α]D 25＝-37.3(c＝1.0,CHCl3).
实施例11：手性苯并吡喃3k的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-甲基-4-氟碘苯(37.8mg)，反应时间为23小时，得手性苯并吡喃产物(S)-3k：无色油状液体，35％产率，94％ee。1H NMR(400MHz,CDCl3):δ7.27(d,J＝3.0Hz,1H),7.24–7.06(m,8H),6.70(dd,J＝8.9,3.0Hz,1H),2.61(s,3H),2.33(s,3H),2.00(s,3H)；13C NMR(100MHz,CDCl3):δ156.41(d,J＝236.2Hz),148.46(d,J＝2.6Hz),144.56,140.37,134.71,132.12,129.08,129.06,128.30(d,J＝8.1Hz),127.86,127.49,126.38,124.83(d,J＝8.8Hz),123.45,116.35(d,J＝23.0Hz),111.63(d,J＝24.7Hz),82.00,28.90,23.56,16.39；19F NMR(376MHz,CDCl3):δ-122.77；HRMS(ESI-TOF):calc’d for C22H20FO[M+H+]319.1493,found 319.1482；HPLC:ChiralpakIA column,hexane,1mL/min,254nm；tR＝6.36min(major),7.17min(minor)；[α]D 25＝-61.0(c＝1.0,CHCl3).
实施例12：手性苯并吡喃3l的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-甲基-4-溴碘苯(47.5mg)，反应时间为18小时，得手性苯并吡喃产物(S)-3l：无色油状液体，44％产率，92％ee。1H NMR(400MHz,CDCl3):δ7.55(d,J＝2.4Hz,1H),7.27(d,J＝2.4Hz,1H),7.25–7.03(m,8H),2.61(s,3H),2.31(s,3H),2.00(s,3H)；13C NMR(100MHz,CDCl3):δ151.61,144.42,140.12,134.70,132.40,132.19,129.04,128.55,127.98,127.93,127.57,127.54,126.33,125.78,123.46,112.69,82.15,28.98,23.58,16.10；HRMS(ESI-TOF):calc’d for C22H20BrO[M+H+]379.0692,found 379.0682；HPLC:Chiralpak IA column,hexane,1mL/min,254nm；tR＝6.21min(major),7.73min(minor)；[α]D 25＝-20.4(c＝1.0,CHCl3).
实施例13：手性苯并吡喃3m的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-甲基-4-硝基碘苯(42.1mg)，反应时间为18小时，得手性苯并吡喃产物(S)-3m：无色油状液体，49％产率，78％ee。1H NMR(400MHz,CDCl3):δ8.43(d,J＝2.7Hz,1H),7.94(dd,J＝2.7,0.9Hz,1H),7.41–7.33(m,2H),7.28(dd,J＝6.4,2.7Hz,1H),7.19–7.12(m,5H),2.69(s,3H),2.44(s,3H),2.09(s,3H)；13CNMR(100MHz,CDCl3):δ158.23,143.81,140.99,139.56,135.10,132.62,128.32,128.13,128.06,127.95,127.74,126.20,125.19,123.97,123.57,121.41,83.46,28.93,23.62,16.42；HRMS(ESI-TOF):calc’d for C22H20NO3[M+H+]346.1438,found 346.1429；HPLC:Chiralpak OD column,hexane:isopropanol＝98:2,1mL/min,254nm；tR＝5.64min(minor),6.21min(major)；[α]D 25＝74.6(c＝1.0,CHCl3).
实施例14：手性苯并吡喃3n的制备
操作步骤同实施例1，区别在于所使用的碘化物为1-溴-4-碘萘(53.3mg)，反应时间为20小时，得手性苯并吡喃产物(S)-3n：无色油状液体，40％产率，89％ee。1H NMR(400MHz,CDCl3):δ8.54–8.45(m,1H),8.13–8.04(m,2H),7.62–7.53(m,2H),7.34–7.22(m,5H),7.09–7.05(m,3H),2.70(s,3H),2.13(s,3H)；13C NMR(100MHz,CDCl3):δ149.80,144.42,139.55,134.21,132.36,131.79,128.67,128.59,127.93,127.88,127.58,127.50,127.22,127.02,126.47,126.15,123.60,122.80,120.17,113.40,82.95,29.09,23.53；HRMS(ESI-TOF):calc’d for C25H20BrO[M+H+]415.0692,found 415.0689；HPLC:ChiralpakOD column,hexane:isopropanol＝98:2,1mL/min,254nm；tR＝4.25min(minor),4.91min(major)；[α]D 25＝124.0(c＝1.0,CHCl3).
实施例15：手性苯并吡喃3o的制备
操作步骤同实施例1，区别在于所使用的碘化物为5-碘-1,2,3,4-四氢萘(41.3mg)，反应时间为11小时，得手性苯并吡喃产物(S)-3o：无色油状液体，39％产率，96％ee。1H NMR(400MHz,CDCl3):δ7.44(d,J＝8.1Hz,1H),7.32–7.28(m,3H),7.24-7.15(m,5H),6.69(d,J＝8.1Hz,1H),2.88(t,J＝5.8Hz,2H),2.78–2.73(m,2H),2.68(s,3H),2.05(s,3H),1.90–1.74(m,4H)；13C NMR(100MHz,CDCl3):δ151.96,145.18,139.85,138.07,134.15,131.91,129.83,127.80,127.33,126.45,126.42,126.22,124.57,123.32,121.15,121.00,81.75,29.65,28.68,23.79,23.66,22.99,22.94；HRMS(ESI-TOF):calc’d for C25H25O[M+H+]341.1900,found 341.1889；HPLC:Chiralpak IA column,hexane,1mL/min,254nm；tR＝6.62min(major),8.16min(minor)；[α]D 25＝27.1(c＝1.0,CHCl3).
实施例16：手性苯并吡喃3p的制备
操作步骤同实施例1，区别在于所使用的碘化物为3-碘-2-甲氧基吡啶(37.6mg)，反应时间为23小时，得手性苯并吡喃产物(S)-3p：无色油状液体，46％产率，90％ee。1H NMR(400MHz,CDCl3):δ7.61(d,J＝5.5Hz,1H),7.34–7.21(m,3H),7.20–7.14(m,2H),7.10–7.00(m,4H),4.00(s,3H),2.56(s,3H),2.00(s,3H)；13C NMR(100MHz,CDCl3):δ155.51,144.02,140.80,138.36,137.49,135.53,132.26,131.80,128.71,127.96,127.56,127.21,126.07,123.71,115.14,82.88,53.92,29.62,23.41；HRMS(ESI-TOF):calc’d for C21H20NO2[M+H+]318.1489,found 318.1477；HPLC:Chiralpak IA column,hexane:isopropanol＝98:2,1mL/min,220nm；tR＝5.07min(major),6.30min(minor)；[α]D 25＝-16.3(c＝1.0,CHCl3).
实施例17：手性苯并吡喃3B和手性叔醇1b的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1b所示(61mg)，反应时间为30小时，得手性苯并吡喃产物(S)-3B：无色油状液体，43％产率，93％ee。1H NMR(400MHz,CDCl3):δ8.50(dd,J＝8.3,1.3Hz,1H),7.81(d,J＝8.7Hz,1H),7.77–7.73(m,1H),7.56–7.46(m,2H),7.40(d,J＝8.7Hz,1H),7.34–7.27(m,3H),7.23–7.18(m,2H),6.89(d,J＝8.0Hz,2H),2.72(s,3H),2.17(s,3H),2.13(s,3H)；13C NMR(100MHz,CDCl3):δ150.05,141.84,140.00,136.96,134.12,133.68,132.12,129.70,128.53,127.42,126.94,126.51,126.14,125.61,125.21,123.43,122.54,119.82,119.22,82.52,29.01,23.70,21.04；HRMS(ESI-TOF):calc’d for C26H23O[M+H+]351.1743,found 351.1738；HPLC:Chiralpak OJcolumn,hexane:isopropanol＝99:1,1mL/min,254nm；tR＝8.36min(minor),13.11min(major)；[α]D 25＝183.0(c＝1.0,CHCl3).手性叔醇(R)-1b：无色油状液体，45％回收率，92％ee。1H NMR(400MHz,CDCl3):δ7.64(dd,J＝7.8,1.7Hz,1H),7.29(t,J＝7.7Hz,1H),7.23(dd,J＝7.5,1.6Hz,1H),7.15(d,J＝8.0Hz,2H),7.09(d,J＝8.0Hz,2H),3.69(s,1H),2.37(s,3H),2.33(s,3H),1.94(s,3H)；13C NMR(100MHz,CDCl3):δ145.44,145.35,140.09,136.41,130.41,128.95,126.95,126.34,125.46,125.32,77.95,31.18,24.45,21.21；HRMS(ESI-TOF):calc’d for C16H17BrNaO[M+Na+]327.0355,found327.0342；HPLC:Chiralpak IAcolumn,hexane:isopropanol＝98:2,1mL/min,220nm；tR＝8.51min(minor),8.98min(major)；[α]D 25＝42.9(c＝1.0,CHCl3).
实施例18：手性苯并吡喃3C和手性叔醇1c的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1c所示(61mg)，醋酸钯(2.2mg，0.01mmol)，三(2-呋喃基)膦(9.2mg，0.04mmol)，反应时间为60小时，得手性苯并吡 喃产物(S)-3C：无色油状液体，49％产率，87％ee。1H NMR(400MHz,CDCl3):δ8.44(dd,J＝8.2,1.3Hz,1H),7.75(d,J＝8.7Hz,1H),7.72–7.66(m,1H),7.52–7.38(m,2H),7.34(d,J＝8.7Hz,1H),7.26–7.18(m,3H),7.10–7.03(m,2H),6.92(t,J＝7.6Hz,1H),6.83(d,J＝7.5Hz,1H),2.67(s,3H),2.08(s,3H),2.06(s,3H)；13C NMR(100MHz,CDCl3):δ150.03,144.76,140.04,137.27,134.11,133.70,132.11,129.68,128.20,127.65,127.42,127.05,126.93,126.51,126.15,125.58,125.21,123.54,123.37,122.55,119.89,119.20,82.67,28.92,23.70,21.56；HRMS(ESI-TOF):calc’d for C26H23O[M+H+]351.1743,found351.1731；HPLC:Chiralpak AD column,hexane:isopropanol＝99:1,1mL/min,220nm；tR＝6.20min(major),6.99min(minor)；[α]D 25＝144.9(c＝1.0,CHCl3).手性叔醇(R)-1c：无色油状液体，39％回收率，>99％ee。1H NMR(400MHz,CDCl3):δ7.63(dd,J＝7.8,1.8Hz,1H),7.29(t,J＝7.6Hz,1H),7.24(dd,J＝7.6,1.7Hz,1H),7.15(dd,J＝16.1,8.5Hz,2H),7.03(dd,J＝13.7,7.6Hz,2H),3.74(s,1H),2.38(s,3H),2.31(s,3H),1.94(s,3H)；13C NMR(100MHz,CDCl3):δ148.35,145.30,140.09,137.82,130.44,128.08,127.58,126.95,126.37,126.19,125.35,122.62,78.06,31.28,24.46,21.76；HRMS(ESI-TOF):calc’d forC16H17BrNaO[M+Na+]327.0355,found 327.0344；HPLC:Chiralpak OJ column,hexane:isopropanol＝99:1,1mL/min,220nm；tR＝13.94min；[α]D 25＝54.7(c＝1.0,CHCl3).
实施例19：手性苯并吡喃3D和手性叔醇1d的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1d所示(61mg)，醋酸钯(2.2mg，0.01mmol)，三(2-呋喃基)膦(9.2mg，0.04mmol)，反应温度为110℃，反应时间为72小时，得手性苯并吡喃产物(S)-3D：白色固体，34％产率，>99％ee。1H NMR(400MHz,CDCl3):δ8.26(d,J＝8.3Hz,1H),7.99(d,J＝8.8Hz,1H),7.81(d,J＝8.1Hz,1H),7.64(dd,J＝7.0,2.1Hz,1H),7.52(d,J＝8.7Hz,1H),7.50–7.46(m,1H),7.44–7.40(m,1H),7.33–7.28(m,2H),7.23–7.17(m,2H),7.04(t,J＝7.6Hz,1H),6.57(d,J＝7.6Hz,1H),2.78(s,3H),2.11(s,3H),1.94(s,3H)；13C NMR(100MHz,CDCl3):δ149.36,142.11,141.62,139.35,133.92,133.53,132.78,131.77,129.01,128.35,127.39,127.33,127.11,126.72,126.39,125.44,125.30,125.20,122.87,122.81,119.75,117.71,83.57,24.92,23.98,22.30；HRMS(ESI-TOF):calc’d for C26H23O[M+H+]351.1743,found 351.1734；HPLC:Chiralpak IA column,hexane,0.5mL/min,230nm；tR＝14.52min(major)；[α]D 25＝-10.6(c＝1.0,CHCl3).手性叔醇 (R)-1d：无色油状液体，36％回收率，85％ee。1H NMR(400MHz,CDCl3):δ7.67(dd,J＝7.8,1.8Hz,1H),7.62(dd,J＝7.2,2.2Hz,1H),7.29(d,J＝7.8Hz,1H),7.23–7.16(m,3H),7.07(dd,J＝6.7,2.3Hz,1H),3.35(s,1H),2.38(s,3H),2.02(s,3H),1.95(s,3H)；13C NMR(100MHz,CDCl3):δ146.00,144.89,139.74,135.21,132.20,129.96,127.15,126.98,126.96,126.15,125.68,124.00,78.18,29.59,24.42,21.66；HRMS(ESI-TOF):calc’d forC16H17BrNaO[M+Na+]327.0355,found 327.0344；HPLC:Chiralpak OD column,hexane:isopropanol＝98:2,1mL/min,210nm；tR＝7.29min(minor),9.19min(major)；[α]D 25＝18.4(c＝1.0,CHCl3).
实施例20：手性苯并吡喃3E和手性叔醇1e的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1e所示(64.2mg)，反应时间为60小时，得手性苯并吡喃产物(S)-3E：无色油状液体，40％产率，93％ee。1H NMR(400MHz,CDCl3):δ8.52–8.44(m,1H),7.81(d,J＝8.7Hz,1H),7.78–7.73(m,1H),7.55–7.46(m,2H),7.40(dd,J＝8.9,0.8Hz,1H),7.35–7.26(m,3H),7.25–7.20(m,2H),6.66–6.55(m,2H),3.64(s,3H),2.72(s,3H),2.13(s,3H)；13C NMR(100MHz,CDCl3):δ158.72,149.96,140.08,136.88,134.14,133.69,132.12,129.73,127.46,127.44,126.95,126.51,126.14,125.61,125.18,123.37,122.50,119.84,119.25,113.12,82.33,55.13,28.95,23.68；HRMS(ESI-TOF):calc’d for C26H23O2[M+H+]367.1693,found 367.1682；HPLC:Chiralpak ADcolumn,hexane:isopropanol＝99:1,1mL/min,254nm；tR＝7.55min(major),10.02min(minor)；[α]D 25＝163.4(c＝1.0,CHCl3).手性叔醇(R)-1e：无色油状液体，47％回收率，86％ee。1H NMR(400MHz,CDCl3):δ7.61(d,J＝7.6Hz,1H),7.25–7.16(m,2H),7.16–7.10(m,2H),6.81–6.73(m,2H),3.75(s,3H),3.58(s,1H),2.33(s,3H),1.90(s,3H)；13C NMR(100MHz,CDCl3):δ158.46,145.42,140.48,140.10,130.39,126.95,126.80,126.28,125.26,113.53,77.73,55.33,31.00,24.48；HRMS(ESI-TOF):calc’d for C16H17BrNaO2[M+Na+]343.0304,found 343.0293；HPLC:Chiralpak AD column,hexane:isopropanol＝95:5,1mL/min,220nm；tR＝12.19min(major),12.88min(minor)；[α]D 25＝37.0(c＝1.0,CHCl3).
实施例21：手性苯并吡喃3F和手性叔醇1f的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1f所示(61.8mg)，反应时间为18小时，得手性苯并吡喃产物(S)-3F：无色油状液体，39％产率，93％ee。1H NMR(400MHz,CDCl3):δ8.39(d,J＝8.3Hz,1H),7.70(dd,J＝15.4,8.2Hz,2H),7.49–7.39(m,2H),7.33(d,J＝8.8Hz,1H),7.26–7.15(m,5H),6.67(t,J＝8.7Hz,2H),2.64(s,3H),2.06(s,3H)；13C NMR(100MHz,CDCl3):δ161.99(d,J＝245.6Hz),149.78,140.58(d,J＝3.0Hz),139.54,134.33,133.70,132.34,129.69,127.89(d,J＝8.0Hz),127.52,127.06,126.63,126.02,125.78,125.12,123.30,122.32,120.06,119.23,114.63(d,J＝21.6Hz),82.14,29.10,23.65；19F NMR(376MHz,CDCl3):δ-115.40；HRMS(ESI-TOF):calc’d for C25H20FO[M+H+]355.1493,found 355.1483；HPLC:Chiralpak IA column,hexane:isopropanol＝98:2,1mL/min,220nm；tR＝4.03min(major),4.27min(minor)；[α]D 25＝136.5(c＝1.0,CHCl3).手 性叔醇(R)-1f：无色油状液体，44％回收率，90％ee。1H NMR(400MHz,CDCl3):δ7.63(dd,J＝7.8,1.8Hz,1H),7.30(t,J＝7.6Hz,1H),7.26–7.19(m,3H),6.95(t,J＝8.7Hz,2H),3.73(s,1H),2.38(s,3H),1.93(s,3H)；13C NMR(100MHz,CDCl3):δ161.77(d,J＝244.9Hz),144.88,144.24(d,J＝3.4Hz),140.29,130.66,127.24(d,J＝8.0Hz),127.08,126.30,125.23,115.00(d,J＝21.1Hz),77.73,31.41,24.45；19F NMR(376MHz,CDCl3):δ-116.43；HRMS(ESI-TOF):calc’d for C15H15BrFO[M+H+]309.0285,found 309.0277；HPLC:Chiralpak IAcolumn,hexane:isopropanol＝98:2,1mL/min,210nm；tR＝8.86min(minor),9.38min(major)；[α]D 25＝49.0(c＝1.0,CHCl3).
实施例22：手性苯并吡喃3G和手性叔醇1g的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1g所示(61.8mg)，反应时间为32小时，得手性苯并吡喃产物(S)-3G：黄色油状液体，47％产率，95％ee。1H NMR(400MHz,CDCl3):δ8.50–8.47(m,1H),7.83(d,J＝8.8Hz,1H),7.73(dd,J＝8.1,1.5Hz,1H),7.52–7.43(m,2H),7.41(d,J＝8.8Hz,1H),7.35–7.28(m,2H),7.26(d,J＝6.8Hz,1H),7.09–7.04(m,1H),6.94–6.90(m,1H),6.88–6.83(m,1H),6.80–6.76(m,1H),2.73(s,3H),2.29(s,3H)；13CNMR(100MHz,CDCl3):δ161.20(d,J＝251.4Hz),149.85,139.32,134.10,133.78,132.33,130.98(d,J＝10.3Hz),129.79,129.71,129.63,129.44(d,J＝3.7Hz),127.19(d,J＝6.6Hz),126.63,126.13,125.50,125.00,123.32,123.12(d,J＝3.6Hz),123.00(d,J＝2.1Hz),120.01,119.00,116.66(d,J＝23.2Hz),81.29(d,J＝2.1Hz),26.04(d,J＝3.8Hz),23.69；19F NMR(376MHz,CDCl3):δ-109.55；HRMS(ESI-TOF):calc’d for C25H20FO[M+H+]355.1493,found 355.1487；HPLC:Chiralpak OD column,hexane:isopropanol＝99:1,1mL/min,220nm；tR＝5.79min(minor),6.35min(major)；[α]D 25＝119.8(c＝1.0,CHCl3).手 性叔醇(R)-1g：无色油状液体，49％回收率，94％ee。1H NMR(400MHz,CDCl3):δ7.75–7.62(m,2H),7.28(t,J＝7.7Hz,1H),7.26–7.20(m,2H),7.17–7.13(m,1H),6.93–6.87(m,1H),3.65(s,1H),2.36(s,3H),2.02(s,3H)；13C NMR(100MHz,CDCl3):δ159.48(d,J＝246.3Hz),145.20,139.73,134.45(d,J＝10.9Hz),130.40,128.99(d,J＝8.6Hz),128.83(d,J＝3.7Hz),127.06,125.80(d,J＝3.1Hz),124.08,123.80(d,J＝3.0Hz),116.15(d,J＝22.5Hz),75.98(d,J＝1.0Hz),29.07(d,J＝1.1Hz),24.49；19F NMR(376MHz,CDCl3):δ-113.04；HRMS(ESI-TOF):calc’d for C15H14BrFNaO[M+Na+]331.0104,found331.0101；HPLC:Chiralpak AD column,hexane:isopropanol＝98:2,1mL/min,210nm；tR＝10.03min(major),10.76min(minor)；[α]D 25＝51.3(c＝1.0,CHCl3).
实施例23：手性苯并吡喃3H和手性叔醇1h的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1h所示(62.2mg)，醋酸钯(2.2mg，0.01mmol)，三(2-呋喃基)膦(9.2mg，0.04mmol)，反应时间为72小时，得手性苯并吡 喃产物(S)-3H：黄色油状液体，21％产率，97％ee。1H NMR(400MHz,CDCl3):δ8.41–8.33(m,1H),7.90(d,J＝8.8Hz,1H),7.81–7.74(m,1H),7.48–7.42(m,3H),7.28(d,J＝7.5Hz,1H),7.20(t,J＝7.6Hz,1H),7.07(d,J＝7.6Hz,1H),6.98(d,J＝5.0Hz,1H),6.72(d,J＝5.0Hz,1H),2.74(s,3H),2.13(s,3H),2.12(s,3H)；13C NMR(100MHz,CDCl3):δ149.59,141.03,140.54,136.39,133.88,133.71,132.39,132.09,129.62,127.41,127.11,126.63,126.09,125.41,125.19,122.88,122.83,122.20,120.00,118.65,80.46,26.72,23.74,15.76；HRMS(ESI-TOF):calc’d for C24H21OS[M+H+]357.1308,found 357.1296；HPLC:Chiralpak IAcolumn,hexane:isopropanol＝99:1,1mL/min,254nm；tR＝5.33min(major),5.84min(minor)；[α]D 25＝51.4(c＝1.0,CHCl3).手性叔醇(R)-1h：黄色油状液体，57％回收率，61％ee。1H NMR(400MHz,CDCl3):δ7.67(dd,J＝7.7,1.8Hz,1H),7.27–7.20(m,1H),7.19(dd,J＝7.6,1.9Hz,1H),7.07(d,J＝5.1Hz,1H),6.67(d,J＝5.1Hz,1H),3.54(s,1H),2.37(s,3H),2.03(s,3H),1.64(s,3H)；13C NMR(100MHz,CDCl3):δ145.38,144.69,140.00,132.64,131.71,130.46,127.11,126.00,124.54,121.86,75.99,30.43,24.58,14.65；HRMS(ESI-TOF):calc’d for C14H15BrNaOS[M+Na+]332.9919,found 332.9914；HPLC:Chiralpak ODcolumn,hexane:isopropanol＝98:2,1mL/min,254nm；tR＝6.83min(minor),8.90min(major)；[α]D 25＝12.0(c＝1.0,CHCl3).
实施例24：手性苯并吡喃3I和手性叔醇1i的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1i所示(66.2mg)，反应时间为50小时，得手性苯并吡喃产物(S)-3I：无色油状液体，43％产率，91％ee。1H NMR(400MHz,CDCl3):δ8.53–8.50(m,1H),7.79(d,J＝8.7Hz,1H),7.75–7.70(m,1H),7.59–7.51(m,1H),7.50–7.43(m,2H),7.40(dd,J＝9.9,1.6Hz,2H),7.37(d,J＝8.9Hz,1H),7.35–7.31(m,3H),7.24–7.18(m,1H),6.54(dd,J＝2.2,1.0Hz,1H),2.73(s,3H),2.18(s,3H)；13C NMR(100MHz,CDCl3):δ154.27,149.98,145.19,140.15,139.58,134.24,133.70,132.20,129.81,127.45,126.97,126.71,126.54,126.13,125.66,125.16,123.56,122.85,122.49,119.90,119.28,119.23,110.74,106.82,82.77,29.43,23.70；HRMS(ESI-TOF):calc’d forC27H20NaO2[M+H+]399.1356,found 399.1346；HPLC:Chiralpak AD column,hexane:isopropanol＝98:2,1mL/min,254nm；tR＝4.69min(major),5.84min(minor)；[α]D 25＝205.5(c＝1.0,CHCl3).手性叔醇(R)-1i：无色油状液体，45％回收率，87％ee。1H NMR(400MHz,CDCl3):δ7.71(dd,J＝7.8,1.8Hz,1H),7.61(d,J＝2.2Hz,1H),7.53(dd,J＝1.9,0.6Hz,1H),7.41–7.39(m,1H),7.32(t,J＝7.6Hz,1H),7.27–7.25(m,1H),7.20(dd,J＝8.6,1.9Hz,1H),6.71(dd,J＝2.2,1.0Hz,1H),3.81(s,1H),2.38(s,3H),2.02(s,3H)；13C NMR(100MHz,CDCl3):δ154.03,145.54,145.46,143.20,140.16,130.45,127.27,126.97,126.32,125.36,122.23,118.22,110.95,106.93,78.21,31.59,24.45；HRMS(ESI-TOF):calc’d for C17H15BrNaO2[M+Na+]353.0148,found 353.0143；HPLC:Chiralpak OD column,hexane:isopropanol＝98:2,1mL/min,254nm；tR＝12.12min(major),14.22min(minor)；[α]D 25＝50.7(c＝1.0,CHCl3).
实施例25：手性苯并吡喃3J和手性叔醇1j的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1j所示(51.4mg)，反应时间为40小时，得手性苯并吡喃产物(S)-3J：白色固体，40％产率，78％ee。1H NMR(400MHz,CDCl3):δ8.44–8.32(m,1H),7.92(d,J＝8.7Hz,1H),7.86–7.79(m,1H),7.54–7.46(m,3H),7.25–7.20(m,2H),7.18–7.09(m,1H),2.72(s,3H),2.24–2.14(m,1H),1.74(s,3H),0.89(dd,J＝14.6,6.8Hz,6H)；13C NMR(100MHz,CDCl3):δ149.13,140.91,133.92,133.87,131.56,128.95,127.49,126.69,126.53,126.10,125.48,125.31,123.25,122.57,119.53,119.01,83.81,31.90,23.81,19.90,18.32,17.08；HRMS(ESI-TOF):calc’d for C22H23O[M+H+]303.1743,found 303.1733；HPLC:Chiralpak OD column,hexane,1mL/min,320nm；tR＝20.94min(minor),31.07min(major)；[α]D 25＝98.0(c＝1.0,CHCl3).手性叔醇(R)-1j：无色油状液体，42％回收率，79％ee。1H NMR(400MHz,CDCl3):δ7.48(dd,J＝7.4,2.3Hz,1H),7.21–7.13(m,2H),3.02–2.91(m,1H),2.59(s,1H),2.44(s,3H),1.67(s,3H),0.88(d,J＝6.8Hz,3H),0.81(d,J＝6.8Hz,3H)；13C NMR(100MHz,CDCl3):δ146.28,139.82,129.74,126.78,126.59,123.04,78.81,33.79,25.16,24.19,17.61,17.18；HRMS(ESI-TOF):calc’dfor C12H17BrNaO[M+Na+]279.0355,found 279.0345；HPLC:Chiralpak AD column,hexane:isopropanol＝98:2,1mL/min,210nm；tR＝6.55min(major),7.30min(minor)；[α]D 25＝7.1(c＝1.0,CHCl3).
实施例26：手性苯并吡喃3K和手性叔醇1k的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1k所示(59.4mg)，反应时间为27小时，得手性苯并吡喃产物(S)-3K：无色油状液体，42％产率，89％ee。1H NMR(400MHz,CDCl3):δ8.41–8.31(m,1H),7.92(d,J＝8.7Hz,1H),7.83–7.79(m,1H),7.54–7.44(m,3H),7.25–7.19(m,2H),7.10(dd,J＝6.0,3.1Hz,1H),2.72(s,3H),1.87–1.77(m,2H),1.75(s,3H),1.71–1.63(m,1H),1.59–1.56(m,2H),1.52(s,1H),1.28–1.13(m,2H),1.11–0.90(m,2H),0.85–0.73(m,1H)；13C NMR(100MHz,CDCl3):δ149.19,140.69,133.90,133.88,131.50,129.00,127.44,126.55,126.49,126.05,125.42,125.34,123.31,122.56,119.43,118.80,83.61,42.43,28.32,27.04,26.76,26.63,26.42,23.88,21.43；HRMS(ESI-TOF):calc’d for C25H27O[M+H+]343.2056,found 343.2045；HPLC:Chiralpak AD column,hexane:isopropanol＝99:1,1mL/min,230nm；tR＝4.61min(major),4.80min(minor)；[α]D 25＝109.9(c＝1.0,CHCl3).手性叔醇(R)-1k：无色油状液体，34％回收率，86％ee。1HNMR(400MHz,CDCl3):δ7.46(dd,J＝7.3,2.4Hz,1H),7.20–7.12(m,2H),2.61(s,1H),2.59–2.54(m,1H),2.45(s,3H),1.79–1.70(m,2H),1.68(s,3H),1.60–1.50(m,3H),1.26–0.98(m,5H)；13C NMR(100MHz,CDCl3):δ146.22,139.77,129.66,126.68,123.07,78.74,44.16,27.76,27.25,26.89,26.85,26.64,25.15,24.66；HRMS(ESI-TOF):calc’d for C15H21BrNaO[M+Na+]319.0668,found 319.0661；HPLC:Chiralpak AD column,hexane:isopropanol＝98:2,1mL/min,210nm；tR＝6.25min(major),7.64min(minor)；[α]D 25＝9.8(c＝1.0,CHCl3).
实施例27：手性苯并吡喃3L和手性叔醇1l的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1l所示(61.4mg)，反应时间为36小时，得手性苯并吡喃产物(S)-3L：白色固体，37％产率，90％ee。1H NMR(400MHz,CDCl3):δ8.53(d,J＝8.3Hz,1H),7.79(t,J＝8.6Hz,2H),7.60–7.45(m,2H),7.40(d,J＝8.8Hz,1H),7.35–7.31(m,2H),7.29(s,3H),7.14–7.05(m,3H),2.71(s,3H),2.52–2.37(m,2H),1.13(t,J＝7.3Hz,3H)；13C NMR(100MHz,CDCl3):δ148.74,142.55,137.40,133.15,132.57,130.83,128.87,126.56,126.35,125.94,125.54,125.46,125.37,124.90,124.52,124.12,122.69,121.23,118.53,117.65,84.02,32.75,22.70,8.04；HRMS(ESI-TOF):calc’d for C26H23O[M+H+]351.1743,found 351.1731；HPLC:Chiralpak AD column,hexane,0.5mL/min,250nm；tR＝12.69min(major),13.41min(minor)；[α]D 25＝214.6(c＝1.0,CHCl3).手性叔醇(R)-1l：无色油状液体，39％回收率，92％ee。1H NMR(400MHz,CDCl3):δ7.72(dd,J＝7.9,1.7Hz,1H),7.38–7.27(m,7H),3.52(s,1H),2.69–2.60(m,1H),2.41(s,3H),2.31–2.22(m,1H),0.93(t,J＝7.3Hz,3H)；13CNMR(100MHz,CDCl3):δ146.83,144.60,140.13,130.26,127.96,126.94,126.77,126.69,126.47,125.45,79.87,33.99,24.59,8.65；HRMS(ESI-TOF):calc’d for C16H17BrNaO[M+Na+]327.0355,found 327.0345；HPLC:Chiralpak IA column,hexane:isopropanol＝98:2,1mL/min,210nm；tR＝7.31min(minor),7.72min(major)；[α]D 25＝49.3(c＝1.0,CHCl3).
实施例28：手性苯并吡喃3M和手性叔醇1m的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1m所示(69.3mg)，反应时间为28小时，得手性苯并吡喃产物(S)-3M：无色油状液体，34％产率，81％ee。1H NMR(400MHz,CDCl3):δ8.54(d,J＝8.4Hz,1H),7.74(dd,J＝15.8,8.5Hz,2H),7.68(t,J＝4.3Hz,1H),7.65–7.58(m,1H),7.56–7.49(m,1H),7.45–7.34(m,5H),7.17–7.10(m,1H),7.07(t,J＝7.5Hz,2H),2.70(s,3H)；13C NMR(100MHz,CDCl3):δ147.39,135.03,134.80,133.80,133.48,131.81,129.88,129.19,128.39,127.81,127.57,127.04,126.40,125.71,124.83,124.76(q,J＝283.0Hz),123.57(q,J＝3.6Hz),122.18,121.08,118.62,84.61(q,J＝28.8Hz),23.90；19F NMR(376MHz,CDCl3):δ-72.69；HRMS(ESI-TOF):calc’d for C25H18F3O[M+H+]391.1304,found 391.1292；HPLC:Chiralpak AD column,hexane,0.5mL/min,250nm；tR＝10.80min(major),11.84min(minor)；[α]D 25＝123.1(c＝1.0,CHCl3).手性叔醇 (R)-1m：黄色油状液体，32％回收率，78％ee。1H NMR(400MHz,CDCl3):δ7.69–7.66(m,1H),7.39–7.31(m,7H),4.21(s,1H),2.38(s,3H)；13C NMR(100MHz,CDCl3):δ141.20,138.52,137.84,131.55,128.67,128.04,127.06(q,J＝4.2Hz),126.94,125.56,124.77(q,J＝284.0Hz),81.81(q,J＝27.9Hz),24.68；19F NMR(376MHz,CDCl3):δ-73.48；HRMS(ESI-TOF):calc’d for C15H12BrF3NaO[M+Na+]366.9916,found366.9901；HPLC:Chiralpak OD column,hexane:isopropanol＝98:2,1mL/min,210nm；tR＝5.29min(major),6.18min(minor)；[α]D 25＝-52.3(c＝1.0,CHCl3).
实施例29：手性苯并吡喃3N和手性叔醇1n的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1n所示(61mg)，反应时间为27小时，得手性苯并吡喃产物(S)-3N：无色油状液体，41％产率，85％ee。1H NMR(400MHz,CDCl3):δ8.52–8.44(m,1H),7.79–7.68(m,2H),7.55–7.51(m,1H),7.49–7.45(m,1H),7.41–7.33(m,3H),7.32–7.26(m,3H),7.11–7.03(m,3H),3.17–2.96(m,2H),2.12(s,3H),1.39(t,J＝7.5Hz,3H)；13C NMR(100MHz,CDCl3):δ150.06,144.77,140.39,140.22,133.75,130.28,129.36,127.79,127.42,127.36,127.09,126.49,126.29,126.23,125.65,125.00,123.28,122.51,120.11,119.00,82.83,29.02,27.75,16.06；HRMS(ESI-TOF):calc’d for C26H23O[M+H+]351.1743,found 351.1742；HPLC:Chiralpak AD column,hexane:isopropanol＝99:1,1mL/min,220nm；tR＝6.99min(major),8.16min(minor)；[α]D 25＝144.0(c＝1.0,CHCl3).手性叔醇(R)-1n：无色油状液体，38％回收率，93％ee。1H NMR(400MHz,CDCl3):δ7.65(dd,J＝7.8,1.6Hz,1H),7.38–7.16(m,7H),3.83(s,1H),2.81–2.67(m,2H),1.95(s,3H),1.18(t,J＝7.5Hz,3H)；13C NMR(100MHz,CDCl3):δ148.59,145.39,145.22,129.12,128.23,127.24,126.75,126.49,125.47,124.80,78.22,31.49,30.36,14.36；HRMS(ESI-TOF):calc’d for C16H17BrNaO[M+Na+]327.0355,found327.0347；HPLC:Chiralpak ODcolumn,hexane:isopropanol＝98:2,1mL/min,210nm；tR＝6.96min(minor),8.39min(major)；[α]D 25＝48.5(c＝1.0,CHCl3).
实施例30：手性苯并吡喃3O和手性叔醇1o的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1o所示(63.2mg)，醋酸钯(2.2mg，0.01mmol)，三(2-呋喃基)膦(9.2mg，0.04mmol)，反应时间为48小时，得手性苯并吡 喃产物(S)-3O：无色油状液体，27％产率，97％ee。1H NMR(400MHz,CDCl3):δ8.47(d,J＝8.2Hz,1H),7.75(d,J＝8.0Hz,1H),7.64–7.47(m,4H),7.47–7.40(m,3H),7.27–7.23(m,2H),7.11–7.03(m,3H),4.17–3.95(m,2H),2.13(s,3H)；13C NMR(100MHz,CDCl3):δ150.70,143.89,140.92,134.08,130.79,130.14,127.96,127.72,127.68,127.65,127.20,126.24,126.21,126.10,126.01,125.73,123.68,122.52,121.03,118.59,117.24,82.92,28.81,24.04；HRMS(ESI-TOF):calc’d for C26H19NNaO[M+Na+]384.1359,found 384.1353；HPLC:Chiralpak IA column,hexane:isopropanol＝95:5,1mL/min,254nm；tR＝10.10min(major),10.90min(minor)；[α]D 25＝106.6(c＝1.0,CHCl3).手性叔醇(R)-1o：无色油状液体，50％回收率，59％ee。1H NMR(400MHz,CDCl3):δ7.91(d,J＝7.8Hz,1H),7.54(d,J＝7.5Hz,1H),7.47(t,J＝7.7Hz,1H),7.31–7.23(m,5H),3.80(s,2H),3.25(s,1H),1.99(s,3H)；13C NMR(100MHz,CDCl3):δ147.15,146.77,132.01,129.13,128.64,128.45,127.88,127.22,125.62,123.88,117.17,77.87,30.24,26.08；HRMS(ESI-TOF):calc’d forC16H14BrNNaO[M+Na+]338.0151,found 338.0147；HPLC:Chiralpak IA column,hexane:isopropanol＝90:10,1mL/min,220nm；tR＝11.73min(major),12.57min(minor)；[α]D 25＝25.5(c＝1.0,CHCl3).
实施例31：手性苯并吡喃3P和手性叔醇1p的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1p所示(84.3mg)，反应时间为30小时，得手性苯并吡喃产物(S)-3P：无色油状液体，39％产率，91％ee。1H NMR(400MHz,CDCl3):δ8.50(d,J＝8.2Hz,1H),7.91(d,J＝8.7Hz,1H),7.76(d,J＝8.0Hz,1H),7.64(dd,J＝7.6,1.4Hz,1H),7.58–7.45(m,2H),7.45–7.39(m,2H),7.36(dd,J＝7.8,1.5Hz,1H),7.35–7.29(m,2H),7.12–7.05(m,3H),5.05–4.85(m,2H),2.14(s,3H),0.99(d,J＝1.3Hz,9H),0.17(d,J＝22.0Hz,6H)；13C NMR(100MHz,CDCl3):δ149.89,144.68,139.69,136.62,134.04,130.23,129.86,127.83,127.42,127.09,126.62,126.26,126.02,125.64,125.53,124.83,122.54,120.34,118.42,82.64,64.73,28.91,26.14,18.60,-4.84,-4.95；HRMS(ESI-TOF):calc’d for C31H34NaO2Si[M+Na+]489.2220,found 489.2212；HPLC:Chiralpak OD column,hexane:isopropanol＝99:1,1mL/min,254nm；tR＝3.65min(minor),6.61min(major)；[α]D 25＝76.8(c＝1.0,CHCl3).手性叔醇(R)-1p：无色油状液体，40％回收率，90％ee。1H NMR(400MHz,CDCl3):δ7.74–7.71(m,1H),7.62–7.56(m,1H),7.43(t,J＝7.7Hz,1H),7.30–7.27(m,1H),7.26–7.20(m,4H),4.66(s,2H),3.58(s,1H),1.96(s,3H),0.96(s,9H),0.11(s,6H)；13C NMR(100MHz,CDCl3):δ148.29,144.64,142.40,128.27,127.22,127.16,127.10,126.87,125.56,121.38,78.02,65.28,31.21,26.08,18.52,-5.21；HRMS(ESI-TOF):calc’d for C21H29BrNaO2Si[M+Na+]443.1012,found 443.1008；HPLC:Chiralpak OD column,hexane:isopropanol＝98:2,1mL/min,210nm；tR＝4.62min(minor),5.86min(major)；[α]D 25＝38.2(c＝1.0,CHCl3).
实施例32：手性苯并吡喃3Q和手性叔醇1q的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1q所示(66.8mg)，反应时间为11小时，得手性苯并吡喃产物(S)-3Q：无色油状液体，42％产率，87％ee。1H NMR(400MHz,CDCl3):δ8.47(dd,J＝8.3,1.2Hz,1H),8.27(d,J＝8.7Hz,1H),7.78–7.70(m,1H),7.53–7.49(m,1H),7.49–7.43(m,2H),7.42–7.39(m,1H),7.36(s,1H),7.35(d,J＝0.6Hz,1H),7.32–7.26(m,2H),7.09–7.01(m,3H),3.80(d,J＝12.7Hz,1H),3.35(d,J＝12.7Hz,1H),2.36(s,6H),2.12(s,3H)；13C NMR(100MHz,CDCl3):δ149.89,144.77,140.02,134.55,134.01,132.60,131.22,127.83,127.37,127.35,126.66,126.53,126.20,125.95,125.49,124.71,122.51,120.20,118.93,82.59,63.28,45.20,28.99；HRMS(ESI-TOF):calc’d forC27H26NO[M+H+]380.2009,found380.2007；HPLC:Chiralpak OD column,hexane:isopropanol＝95:5,1mL/min,254nm；tR＝4.11min(minor),4.67min(major)；[α]D 25＝119.7(c＝1.0,CHCl3).手性叔醇(R)-1q：无色油状液体，40％回收率，99％ee。1H NMR(400MHz,CDCl3):δ7.73(dd,J＝7.7,1.9Hz,1H),7.45(dd,J＝7.6,1.9Hz,1H),7.38(t,J＝7.6Hz,1H),7.30–7.26(m,1H),7.26–7.18(m,4H),3.62–3.38(m,2H),2.27(s,6H),1.95(s,3H)；13C NMR(100MHz,CDCl3):δ148.41,145.35,140.09,130.51,128.26,127.60,127.01,126.78,125.47,125.03,78.16,64.16,45.67,31.38；HRMS(ESI-TOF):calc’d forC17H21BrNO[M+H+]334.0801,found 334.0799；HPLC:Chiralpak OD column,hexane:isopropanol＝98:2,1mL/min,220nm；tR＝8.24min(minor),9.03min(major)；[α]D 25＝50.9(c＝1.0,CHCl3).
实施例33：手性苯并吡喃3R和手性叔醇1r的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1r所示(72mg)，反应时间为11小时，得手性苯并吡喃产物(S)-3R：无色油状液体，43％产率，91％ee。1H NMR(400MHz,CDCl3):δ8.51(d,J＝8.8Hz,1H),8.32(d,J＝8.7Hz,1H),7.76(d,J＝7.5Hz,1H),7.59–7.45(m,3H),7.43(d,J＝8.7Hz,1H),7.37–7.33(m,4H),7.15–7.01(m,3H),4.09(d,J＝12.7Hz,1H),3.50(d,J＝12.7Hz,1H),2.70–2.67(m,4H),2.15(s,3H),1.86–1.83(m,4H)；13C NMR(100MHz,CDCl3):δ149.84,144.81,139.93,135.36,133.99,131.89,130.77,127.83,127.37,127.32,126.84,126.59,126.47,126.21,125.93,125.45,124.48,122.48,120.17,119.03,82.65,59.73,53.92,29.05,23.67；HRMS(ESI-TOF):calc’d for C29H28NO[M+H+]406.2165,found 406.2170；HPLC:Chiralpak OD column,hexane:isopropanol＝95:5,1mL/min,254nm；tR＝4.19min(minor),4.87min(major)；[α]D 25＝67.3(c＝2.0,CHCl3).手性 叔醇(R)-1r：无色油状液体，40％回收率，97％ee。1H NMR(400MHz,CDCl3):δ7.69(dd,J＝7.8,1.7Hz,1H),7.52(dd,J＝7.6,1.7Hz,1H),7.38(t,J＝7.7Hz,1H),7.31–7.18(m,5H),3.79(s,1H),3.75–3.63(m,2H),2.60–2.56(m,4H),1.95(s,3H),1.82–1.77(m,4H)；13C NMR(100MHz,CDCl3):δ148.53,144.99,140.84,129.91,128.24,127.24,127.04,126.77,125.47,124.37,78.18,60.45,54.43,31.51,23.77；HRMS(ESI-TOF):calc’d forC19H23BrNO[M+H+]360.0958,found 360.0959；HPLC:Chiralpak OD column,hexane:isopropanol＝95:5,1mL/min,210nm；tR＝6.57min(minor),7.88min(major)；[α]D 25＝42.3(c＝2.0,CHCl3).
实施例34：手性苯并吡喃3S和手性叔醇1s的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1s所示(75.2mg)，反应时间为10小时，得手性苯并吡喃产物(S)-3S：无色油状液体，46％产率，92％ee。1H NMR(400MHz,CDCl3):δ8.51(d,J＝8.2Hz,1H),8.34(d,J＝8.7Hz,1H),7.76(d,J＝7.5Hz,1H),7.57–7.47(m,3H),7.43–7.36(m,3H),7.35–7.30(m,2H),7.13–7.08(m,3H),3.88–3.73(m,5H),3.52(d,J＝12.8Hz,1H),2.74–2.53(m,4H),2.15(s,3H)；13C NMR(100MHz,CDCl3):δ149.94,144.71,140.25,134.03,133.17,132.60,131.41,127.84,127.39,127.36,126.61,126.53,126.42,126.16,125.93,125.57,124.82,122.49,120.13,118.85,82.64,67.23,62.45,53.40,29.02；HRMS(ESI-TOF):calc’d for C29H28NO2[M+H+]422.2115,found422.2109；HPLC:Chiralpak OD column,hexane:isopropanol＝90:10,1mL/min,220nm；tR＝5.93min(minor),7.24min(major)；[α]D 25＝71.6(c＝2.0,CHCl3).手性叔醇(R)-1s：白色固体，45％回收率，92％ee。1H NMR(400MHz,CDCl3):δ7.72(dd,J＝7.8,1.7Hz,1H),7.51(dd,J＝7.7,1.7Hz,1H),7.38(t,J＝7.7Hz,1H),7.32–7.20(m,5H),3.77(s,1H),3.71(t,J＝4.6Hz,4H),3.62–3.47(m,2H),2.49(t,J＝4.6Hz,4H),1.95(s,3H)；13C NMR(100MHz,CDCl3):δ148.39,145.39,139.38,130.07,128.26,127.56,126.97,126.82,125.46,124.93,78.15,67.19,62.97,53.77,31.39；HRMS(ESI-TOF):calc’d for C19H23BrNO2[M+H+]376.0907,found 376.0902；HPLC:Chiralpak AD column,hexane:isopropanol＝80:20,1mL/min,210nm；tR＝6.39min(major),6.98min(minor)；[α]D 25＝37.8(c＝2.0,CHCl3).
实施例35：手性苯并吡喃3T和手性叔醇1t的制备
操作步骤同实施例1，区别在于所使用的消旋芳基叔醇如1t所示(65.4mg)，反应时间为20小时，得手性苯并吡喃产物(S)-3T：白色固体，40％产率，91％ee。1H NMR(400MHz,CDCl3):δ8.70–8.64(m,1H),8.53–8.48(m,1H),8.04(d,J＝8.6Hz,1H),7.97–7.92(m,1H),7.90–7.86(m,1H),7.82–7.76(m,1H),7.61–7.53(m,3H),7.53–7.47(m,3H),7.44–7.38(m,2H),7.15–7.08(m,3H),2.21(s,3H)；13C NMR(100MHz,CDCl3):δ150.17,144.49,137.69,134.27,133.88,129.15,128.77,127.91,127.78,127.63,127.60,127.54,126.71,126.66,126.48,126.42,126.17,126.02,125.79,125.49,123.38,122.56,120.46,118.73,83.30,28.19；HRMS(ESI-TOF):calc’d for C28H21O[M+H+]373.1587,found 373.1581；HPLC:Chiralpak IA column,hexane:isopropanol＝99:1,1mL/min,254nm；tR＝12.75min(major),20.79min(minor)；[α]D 25＝193.8(c＝1.0,CHCl3).手性叔醇(R)-1t：无色油状液体，44％回收率，89％ee。1H NMR(400MHz,CDCl3):δ8.33–8.27(m,1H),8.00(d,J＝8.7Hz,1H),7.90(d,J＝8.7Hz,1H),7.85(dd,J＝7.3,2.0Hz,1H),7.56–7.49(m,2H),7.34–7.27(m,3H),7.25–7.18(m,2H),3.68(s,1H),2.07(s,3H)；13C NMR(100MHz,CDCl3):δ148.45,143.61,134.03,133.25,128.32,128.13,127.84,127.77,127.43,126.96,126.92,125.74,125.43,123.15,78.40,30.90；HRMS(ESI-TOF):calc’d for C18H15BrNaO[M+Na+]349.0198,found 349.0196；HPLC:Chiralpak IA column,hexane:isopropanol＝98:2,1mL/min,220nm；tR＝13.24min(minor),13.76min(major)；[α]D 25＝6.0(c＝1.0,CHCl3).
以上所述，仅为本发明较佳的具体实施方式，但本发明保护的范围并不局限于此，任何熟悉本技术领域的技术人员在本发明揭露的技术范围内所做的任何修改，等同替换和改进等，均应包含在发明的保护范围之内。
Claims (5)
1.一种基于动力学拆分策略合成手性芳基叔醇和苯并吡喃类化合物的方法，其特征在于，包括以下步骤：
在保护气体氛围下，以消旋的芳基叔醇A和芳基碘化物B为起始原料，在钯催化剂C、膦配体D、手性降冰片烯衍生物E和碱F的作用下，于有机溶剂G中搅拌反应完全，反应结束后分离反应物即可得到手性芳基叔醇和苯并吡喃类化合物；
所述芳基叔醇A结构式为：
所述芳基碘化物B的结构式为：
其中，R1-R4为芳基、杂环芳基、烷基、烷氧基、卤素中的一种或几种；x表示R1的个数，0≤x≤4；y表示R4的个数，0≤y≤4；Ar1为苯环或萘环；和Ar2为苯环、萘环或吡啶环；
所述钯催化剂C为Pd(PPh3)4、Pd(dba)2、Pd2(dba)3、Pd(OAc)2、Pd(PhCN)2Cl2、Pd(MeCN)2Cl2、PdCl2、PdI2、[Pd(allyl)Cl]2中的任意一种或几种；
所述的膦配体D为三芳基膦、三烷基膦、二环己基(2',4',6'-三异丙基-[1,1'-二苯基]-2-基)膦、二环己基(2',4',6'-三异丙基-3,6-二甲氧基-[1,1'-二苯基]-2-基)膦、二环己基(2',6'-二甲氧基-[1,1'-二苯基]-2-基)膦、2'-(二环己基膦基)-N,N-二甲基-[1,1'-二苯基]-2-胺、二环己基(2',6'-二异丙氧基-[1,1'-二苯基]-2-基)膦、三(2-呋喃基)膦、(3S,5S,7S)-金刚烷-1-基((1R,5S)-金刚烷-2-基)(丁基)膦中的任意一种或几种；
所述手性降冰片烯衍生物E的结构式为：
所述的碱F为碳酸锂、碳酸钠、碳酸钾、碳酸铯、醋酸钠、醋酸钾、醋酸铯、磷酸三钾、甲酸钾、碳酸氢钠、碳酸氢钾、氢氧化钠、氢氧化钾、叔丁醇钠、叔丁醇钾中的任意一种或几种；
所述的有机溶剂G为甲醇、乙醇、异丙醇、叔丁醇、四氢呋喃、2-甲基四氢呋喃、乙醚、二甲基乙二醚、甲基叔丁基醚、1,4-二氧六烷、1,3-二氧六烷、二氯甲烷、1,2-二氯乙烷、氯仿、四氯化碳、C4-12的饱和烷烃、C3-12的氟代或者氯代烷烃、苯、甲苯、二甲苯、三甲苯、二甲亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、丙酮、N-甲基吡咯烷酮、乙腈、C3-12的饱和烷基腈中的任意一种或几种。
2.根据权利要求1所述的方法，其特征在于，所述反应温度为50-130℃，反应时间为5-72h。
3.根据权利要求1所述的方法，其特征在于，所述分离反应物的方法为：将反应混合物过滤、浓缩和柱层析纯化。
4.根据权利要求1所述的方法，其特征在于，所述产物手性芳基叔醇的结构为：
5.根据权利要求1所述的方法，其特征在于，所述产物苯并吡喃类化合物的结构为：
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