CN112125770A - 一种硅中心手性二氢苯并噻咯及其制备方法 - Google Patents
一种硅中心手性二氢苯并噻咯及其制备方法 Download PDFInfo
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- CN112125770A CN112125770A CN202010836524.XA CN202010836524A CN112125770A CN 112125770 A CN112125770 A CN 112125770A CN 202010836524 A CN202010836524 A CN 202010836524A CN 112125770 A CN112125770 A CN 112125770A
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- 238000002360 preparation method Methods 0.000 title claims description 9
- 238000000034 method Methods 0.000 claims abstract description 70
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 37
- 150000001875 compounds Chemical class 0.000 claims abstract description 34
- -1 phenoxyethyl Chemical group 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 7
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 7
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims abstract description 6
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 5
- 150000002367 halogens Chemical class 0.000 claims abstract description 5
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000002933 cyclohexyloxy group Chemical class C1(CCCCC1)O* 0.000 claims abstract description 4
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 4
- BLRHMMGNCXNXJL-UHFFFAOYSA-N 1-methylindole Chemical group C1=CC=C2N(C)C=CC2=C1 BLRHMMGNCXNXJL-UHFFFAOYSA-N 0.000 claims abstract description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 3
- 150000003222 pyridines Chemical class 0.000 claims abstract description 3
- 125000001544 thienyl group Chemical group 0.000 claims abstract description 3
- YMSWJBZPRYKQHJ-UHFFFAOYSA-N triethylgermanium Chemical group CC[Ge](CC)CC YMSWJBZPRYKQHJ-UHFFFAOYSA-N 0.000 claims abstract description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 88
- 239000010948 rhodium Substances 0.000 claims description 60
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 239000003446 ligand Substances 0.000 claims description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- 239000003054 catalyst Substances 0.000 claims description 13
- 229910052703 rhodium Inorganic materials 0.000 claims description 9
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 7
- 239000000463 material Substances 0.000 abstract description 3
- 238000010189 synthetic method Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 272
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 130
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 113
- HEDRZPFGACZZDS-UHFFFAOYSA-N CHCl3 Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 77
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 76
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 67
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- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 41
- 238000004364 calculation method Methods 0.000 description 37
- 239000003480 eluent Substances 0.000 description 37
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 32
- 239000000243 solution Substances 0.000 description 14
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- 238000004293 19F NMR spectroscopy Methods 0.000 description 10
- 238000000132 electrospray ionisation Methods 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- 238000010898 silica gel chromatography Methods 0.000 description 7
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- 239000007787 solid Substances 0.000 description 7
- QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 6
- 150000001336 alkenes Chemical class 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 229910052710 silicon Inorganic materials 0.000 description 6
- 239000010703 silicon Substances 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 5
- 239000012300 argon atmosphere Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene chloride Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 229910052723 transition metal Inorganic materials 0.000 description 5
- 150000003624 transition metals Chemical class 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 description 4
- 238000000375 direct analysis in real time Methods 0.000 description 4
- 238000012063 dual-affinity re-targeting Methods 0.000 description 4
- VGIYPVFBQRUBDD-UHFFFAOYSA-N ethenoxycyclohexane Chemical compound C=COC1CCCCC1 VGIYPVFBQRUBDD-UHFFFAOYSA-N 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 4
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- 229920006395 saturated elastomer Polymers 0.000 description 4
- 150000004756 silanes Chemical class 0.000 description 4
- SCPYDCQAZCOKTP-UHFFFAOYSA-N silanol Chemical class [SiH3]O SCPYDCQAZCOKTP-UHFFFAOYSA-N 0.000 description 4
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
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- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
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- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
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- JFOZKMSJYSPYLN-QHCPKHFHSA-N lifitegrast Chemical compound CS(=O)(=O)C1=CC=CC(C[C@H](NC(=O)C=2C(=C3CCN(CC3=CC=2Cl)C(=O)C=2C=C3OC=CC3=CC=2)Cl)C(O)=O)=C1 JFOZKMSJYSPYLN-QHCPKHFHSA-N 0.000 description 1
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
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- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
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- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical group OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 1
- 229960002797 pitavastatin Drugs 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
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- 229930192474 thiophene Natural products 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- UKRDPEFKFJNXQM-UHFFFAOYSA-N vinylsilane Chemical compound [SiH3]C=C UKRDPEFKFJNXQM-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
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- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
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Abstract
Description
技术领域
本发明属于有机合成领域,具体涉及一种硅中心手性二氢苯并噻咯及其制备方法。
背景技术
有机硅化合物在材料科学、农业科学和药物化学中具有广泛的应用,但对映选择性合成硅中心手性的有机硅化合物还鲜有报道。在不对称合成中,构建硅中心手性是最具挑战性的课题之一,传统方法通常需要利用手性试剂或底物的控制来合成对映体富集的硅中心手性硅烷,但对映选择性一般难以控制。在过去的十多年里,人们开始致力于手性过渡金属催化剂的设计和开发,提供了一些去对称化的方法,实现了将手性二氢硅烷或四取代有机硅烷转化为硅中心手性硅烷。
鉴于C-H键的广泛存在和手性在有机分子中的重要性,对C-H键进行直接的对映选择性的官能化具有重要意义。在过去的十年中,手性过渡金属催化取得了显著进展,但未活化的C(sp3)-H键的对映选择性官能化仍处于起步阶段。在各种C-H官能化方法中,将C(sp3)-H键转化为C(sp3)-Si键的C-H硅基化反应很有价值。该过程通常是通过Si-H键氧化加成到金属中心而引发的,进而将金属原子传递到近端的C-H位点,从而允许选择性的C-H键活化发生。Hartwig课题组在该方向做出了领先的研究,并成功开发了两个对映选择性反应,用于未活化的C(sp3)-H键的硅基化,成功构建了碳立体中心手性。然而,关于硅立体中心的不对称C(sp3)-H硅基化反应,据发明人所知,仅有一个例子,即Takai及其同事以中等收率、40%ee合成的一种特殊螺硅双茚满化合物。
因此,有必要设计和开发通用的脂肪族C-H键的对映选择性硅基化的有效策略。
发明内容
发明人认为,合适的手性过渡金属催化剂与二氢硅烷底物可以引发对映选择性分子内C(sp3)-H硅基化,得到不对称单氢硅烷。为了避免在高活性过渡金属存在下形成的单氢硅烷分解或外消旋化,可以利用适当的反应试剂来捕获单氢硅烷,得到不对称的四取代的硅立体中心手性硅烷。该反应成功的关键在于精确控制反应顺序,因为在过渡金属催化的条件下,二氢硅烷通常比单氢硅烷反应活性更高。
本发明的目的是提供一种硅中心手性二氢苯并噻咯。
本发明的另一目的是提供硅中心手性二氢苯并噻咯的制备方法。
为达到上述目的之一,本发明采用以下技术方案:
一种硅中心手性二氢苯并噻咯化合物,其具有通式I的结构:
R3选自苯基、苄基、噻吩基、萘基、苯并呋喃、N-甲基吲哚、吗啉或三甲基硅基取代的苯基;
R5选自卤素、烷氧基或者苯环,该苯环与相连的苯环稠环成萘。
R5作为苯环或萘环的取代基,可以是单取代,也可以是多取代,当存在2个以上取代基时,取代基的种类可以相同或不同。
进一步地,所述取代苯基为卤素、三氟甲基、甲氧基或频哪醇硼取代的苯基,可以是单取代,也可以是多取代,当存在2个以上取代基时,取代基的种类可以相同或不同。
进一步地,所述化合物选自以下化合物中之一:
一种上所述的化合物的制备方法,包括以下步骤:在配体和铑催化剂存在下,式II化合物和式III化合物反应如下
所述铑催化剂选自[Rh(cod)Cl]2、[Rh(cod)OH]2或[Rh(nbd)Cl]2;
所述配体选自以下化合物之一:
R、R’各自独立地选自苯基、3,5-二甲基-4-甲氧基苯基、3,5-二甲基苯基、环己基、叔丁基、4-三氟甲基苯基或2-甲基苯基。
进一步地,所述配体选自以下化合物之一:
进一步地,所述配体的用量至少是4mol%,所述铑催化剂的用量至少是2mol%。配体、铑催化剂的用量的基准是相对于原料式II化合物的用量,比如,配体的用量写成4mol%的形式,指每1mol式II化合物使用0.04mol配体;铑催化剂的用量写成2mol%的形式,指每1mol式II化合物使用0.02mol铑催化剂。
进一步地,所述式II化合物和式III化合物的摩尔比为1∶(1~3)。
进一步地,所述反应以甲苯、二氯乙烷、正己烷、1,4-二氧六环中的至少一种为溶剂。
进一步地,所述反应的时间至少是1h。
进一步地,所述反应的温度为100℃以上。
本文所用的“烷基”指饱和脂肪族烃基团,其为包含1至20个碳原子的直链或支链基团,优选含有1至12个碳原子的烷基,更优选含有1至6个碳原子的烷基。烷基基团的实例包括甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、戊基、2-戊基、异戊基、新戊基、己基、2-己基、3-己基、3-甲基戊基。
本文所用的“烷氧基”指-O-(烷基)和-O-(环烷基),其中烷基、环烷基的定义如本文所述,烷氧基的非限制性实例包括:甲氧基、乙氧基、丙氧基、异丙氧基、正丁氧基、仲丁氧基、叔丁氧基、戊氧基、2-戊氧基、异戊氧基、新戊氧基、己氧基、2-己氧基、3-己氧基、3-甲基戊氧基、环丙氧基、环丁氧基、环戊氧基、环己氧基。烷氧基基团通常具有通过氧桥连接的1至7个碳原子。
本文所用的“卤素”指氟、氯、溴和碘。
本文所用的“三氟甲基”指-CF3。
本文所用的“苯氧乙基”指PhOCH2CH2-。
本文所用的“取代苯基”指被其他官能团所取代的苯基。
本发明具有以下有益效果:
本发明提供了铑催化的脂肪族C-H键的对映选择性硅基化反应,合成硅立体中心手性的二氢苯并噻咯,反应涉及二氢硅烷的高度对映选择性的分子内C(sp3)-H硅基化,然后发生立体控制的分子间烯烃硅氢化反应,从而形成不对称的四取代硅烷。具有不同官能团的二氢硅烷和烯烃均适用本发明的合成方法,以优异的收率和对映选择性获得了多种高度官能化的硅中心手性二氢苯并噻咯化合物。本发明的产物和方法可以在合成化学、药物化学和材料科学中得到广泛应用。
具体实施方式
在氩气保护、磁力搅拌条件下进行常规反应。在氩气保护、无色5mL微波反应管中进行催化反应。由惰性溶剂纯化系统(Et2O,CH2Cl2,THF和甲苯)获得无水溶剂。使用黄海HSGF254板上进行TLC薄层色谱,通过荧光猝灭(λmax=254nm)对显影的色谱显色。使用GENERAR-REAGENT硅胶(200~300目)进行硅胶柱色谱。在没有特别说明的情况下,所有试剂均购自商业供应商,无需进一步纯化即可直接使用。核磁共振(NMR)光谱是在室温下使用Bruker DPX 400或Bruker DPX 600仪器记录1H NMR(400或600MHz),记录1C NMR(100或125MHz),记录19F NMR(376MHz或565MHz)。化学位移(δ)以ppm表示,偶合常数(J)以赫兹(Hz)表示。NMR标准如下:(1H NMR)CDCl3=7.26ppm;(13C NMR)CDCl3=77.00ppm。1H NMR数据记录如下:δ表示化学位移,s表示单峰,d表示双峰,dd表示双二重峰,t表示三重峰,q表示四重峰,m表示多重峰,br表示宽峰,偶合常数单位是Hz。以化学位移(δ,ppm)记录13C NMR。用Agilent 1260系列记录手性HPLC色谱图。在电子碰撞电离(EI)、电喷雾电离(ESI)或者实时直接分析条件下,使用Waters Premier GC-TOF MS、Agilent Technologies 7250 GCQTOF、Agilent Technologies 6230 TOF LC/MS、Thermo Fisher Scientific LTQ FT Ultra记录高分辨率质谱(HRMS)。在Rudolph Autopol-I自动旋光仪上测量旋光度,样品在CHCl3中的浓度为1.0g/100mL。
实施例1
二氢硅烷底物的合成
方法A:在氩气气氛、0℃下,在5min内向S1的THF溶液中滴加R3SiH2Cl(1.5当量)(根据现有文献制备M.D.Visco,J.M.Wieting,A.E.Mattson,Org Lett 2016,18,2883-2885.),然后在70℃下搅拌3h,冷却至室温后,将反应混合物用饱和NH4Cl溶液淬灭,并用EtOAc萃取,真空浓缩,残余物通过硅胶柱色谱纯化,得到化合物S5。
方法B:在氩气气氛、-78℃下,在10分钟内向S2的THF溶液中逐滴添加R3SiH2Cl(1.5当量),所得混合物在-78℃下继续搅拌1h,然后将混合物温热至室温并搅拌2小时,将反应混合物用饱和NH4Cl溶液淬灭,并用EtOAc萃取,真空浓缩,残余物通过硅胶柱色谱纯化,得到化合物S5。
方法C:在氩气气氛、0℃下,在5分钟内向R3MgBr的THF溶液中逐滴添加S3(1.5当量),然后在70℃搅拌3h,冷却至室温后,将反应混合物用饱和NH4Cl溶液淬灭,并用EtOAc萃取,真空浓缩,残余物通过硅胶柱色谱纯化,得到化合物S5。
方法D:向干燥的小瓶中添加镁粉(3.0当量),用螺帽密封,并用氩气吹扫,然后添加THF。向干燥的小瓶中添加PhCH2Br(1.0当量)、THF和S4(1.5当量)。将含有镁粉的反应瓶置于超声仪水浴中,并在室温下进行超声处理。开始超声处理后,立即将1,2-二溴乙烷(0.5当量)添加到反应瓶中,然后添加包含PhCH2Br、S4和THF的溶液。将反应混合物在室温下超声30分钟,之后用饱和NH4Cl水溶液淬灭,用Et2O萃取(3×),Na2SO4干燥并真空浓缩,残余物通过硅胶柱色谱纯化,得到化合物S5。
根据方法A制备,以80%的收率得到化合物1a(4.5g,18.7mmol),为无色油状物(Rf=0.8,石油醚)。
1H NMR(600MHz,CDCl3)δ7.65(dd,J=7.2,1.6Hz,1H),7.56-7.49(m,3H),7.39(ddq,J=7.9,4.5,2.0Hz,2H),7.34(dd,J=7.9,6.4Hz,2H),7.19(td,J=7.3,1.2Hz,1H),5.22(s,2H),1.44(s,9H)。13C NMR(151MHz,CDCl3)δ157.51,157.51,139.74,135.48,133.37,129.94,129.50,128.87,127.99,125.73,124.94,37.26,32.22。
根据方法A制备,以54%的收率得到化合物1b(0.91g,3.5mmol),为无色油状物(Rf=0.8,石油醚)。
1H NMR(400MHz,CDCl3)δ7.55-7.50(m,2H),7.47(dd,J=8.8,5.4Hz,1H),7.44-7.34(m,3H),7.31(dd,J=9.2,3.0Hz,1H),7.02(ddd,J=8.9,7.9,3.0Hz,1H),5.20(s,2H),1.42(s,9H)。13C NMR(151MHz,CDCl3)δ159.95(d,J=247.4Hz),153.13(d,J=3.3Hz),135.47,132.46,131.86(d,J=3.3Hz),129.79,128.14,127.54(d,J=6.3Hz),125.66(d,J=19.5Hz),116.04(d,J=19.5Hz),36.93,32.39。19F NMR(376MHz,CDCl3)δ-119.01。
根据方法A制备,以66%收率得到化合物1c(1.18g,4.3mmol),为无色油状物(Rf=0.8,石油醚)。
1H NMR(400MHz,CDCl3)δ7.60(d,J=2.3Hz,1H),7.52(dt,J=7.7,1.4Hz,2H),7.48-7.29(m,5H),5.20(s,2H),1.41(s,9H)。13C NMR(151MHz,CDCl3)δ155.86,138.88,135.43,132.34,131.85,131.03,129.80,129.68,128.15,127.45,37.04,32.18。
根据方法A制备,以69%的收率得到化合物1d(1.12g,4.1mmol),为无色油状物(Rf=0.4,石油醚)。
1H NMR(400MHz,CDCl3)δ7.56-7.50(m,2H),7.44(d,J=8.8Hz,1H),7.40-7.32(m,3H),7.20(d,J=3.0Hz,1H),6.89(dd,J=8.8,3.0Hz,1H),5.20(s,2H),3.76(s,3H),1.41(s,9H)。13C NMR(151MHz,CDCl3)δ156.24,149.52,135.48,133.13,130.32,129.55,128.02,126.95,125.60,114.09,55.09,36.58,32.47。
根据方法B制备,以85%的收率得到化合物1e(0.9g,3.1mmol),为无色油状物(Rf=0.6,石油醚)。
1H NMR(600MHz,CDCl3)δ8.27(d,J=8.5Hz,1H),7.98(d,J=8.8Hz,1H),7.88(dd,J=8.1,1.5Hz,1H),7.85(d,J=8.8Hz,1H),7.65-7.57(m,2H),7.46(ddd,J=8.1,6.7,1.1Hz,1H),7.41(ddd,J=8.5,6.7,1.4Hz,2H),7.39-7.34(m,2H),5.63(s,2H),1.67(s,9H)。13C NMR(151MHz,CDCl3)δ158.43,139.08,135.38,132.49,131.26,130.73,129.47,128.38,128.03,127.79,125.89,125.26,124.86,124.64,37.86,33.29。
根据步骤A制备,以76%的收率得到化合物1f(1.6g,6.0mmol),为无色油状物(Rf=0.8,石油醚)。
1H NMR(600MHz,CDCl3)δ7.67(dd,J=7.2,1.2Hz,1H),7.53(dt,J=6.7,1.5Hz,2H),7.41-7.30(m,5H),7.17(dt,J=7.4,4.3Hz,1H),5.19(s,2H),2.00(dq,J=14.7,7.4Hz,2H),1.60(dq,J=14.7,7.4Hz,2H),1.32(s,3H),0.55(t,J=7.4Hz,6H)。13C NMR(151MHz,CDCl3)δ154.34,140.00,135.48,133.37,129.59,129.44,129.25,128.34,127.92,124.67,44.23,35.01,24.66,8.75。
按照方法A制备,以76%的收率得到化合物1g(1.16g,3.6mmol),为无色油状物(Rf=0.8,石油醚)。
1H NMR(400MHz,CDCl3)δ7.70(dd,J=7.4,1.6Hz,1H),7.54(ddd,J=10.9,7.9,1.4Hz,3H),7.42-7.29(m,4H),7.20(td,J=7.3,1.2Hz,1H),5.22(s,2H),2.21-2.08(m,2H),1.60(s,3H),1.41-1.30(m,2H),0.30(ttd,J=8.9,4.8,4.2,2.6Hz,4H),0.11(tdd,J=8.6,5.5,4.2Hz,2H),-0.04(ddt,J=7.8,5.3,2.7Hz,2H),-0.19--0.30(m,2H)。13C NMR(151MHz,CDCl3)δ155.57,139.99,135.51,133.32,129.69,129.44,129.22,128.10,127.94,124.74,47.74,46.18,26.32,6.85,5.84,3.64。
根据方法A制备,以78%的收率得到化合物1h(1.5g,5.3mmol),为无色油状物(Rf=0.8,石油醚)。
1H NMR(400MHz,CDCl3)δ7.70(d,J=7.4Hz,1H),7.58-7.47(m,3H),7.44-7.31(m,4H),7.23-7.17(m,1H),5.21(s,2H),2.16(dd,J=12.7,6.6Hz,2H),1.71-1.61(m,2H),1.50-1.34(m,6H),1.32(s,3H)。13C NMR(101MHz,CDCl3)δ156.50,140.27,135.46,133.32,129.98,129.44,129.14,127.93,126.95,124.72,40.64,39.27,29.67,26.14,22.69。
根据方法B制备,以78%的收率得到化合物1i(0.8g,1.8mmol),为无色油状物(Rf=0.4,石油醚/乙酸乙酯=60∶1)。
1H NMR(400MHz,CDCl3)δ7.72(d,J=7.3Hz,1H),7.54-7.47(m,2H),7.44(d,J=8.0Hz,1H),7.36(td,J=7.7,1.6Hz,1H),7.30-7.12(m,8H),6.86(t,J=7.3Hz,2H),6.66(d,J=8.1Hz,4H),5.24(s,2H),3.74(td,J=8.9,6.0Hz,2H),3.56(td,J=8.9,5.5Hz,2H),2.58(ddd,J=14.1,8.5,5.6Hz,2H),2.20(ddd,J=14.3,8.5,6.0Hz,2H),1.60(s,3H)。13CNMR(151MHz,CDCl3)δ158.63,152.36,140.40,135.38,132.39,130.16,129.71,129.43,129.22,128.06,127.76,125.56,120.40,114.33,64.37,41.88,41.85,26.60。
在氩气气氛下,将TiCl4(11mL,1M的CH2Cl2,1.1当量)加入无水CH2Cl2(30mL)中,并冷却至-40℃,然后滴加Me2Zn溶液(11mL,1M的己烷,1.1当量),搅拌15分钟后,滴加1j″(3.56g,10mmol,根据报道的文献制备M.Romain,D.Tondelier,J.C.Vanel,B.Geffroy,O.Jeannin,J.Rault-Berthelot,R.Metivier,C.Poriel,Angew.Chem.Int.Ed.2013,52,14147-14151.;S.B.Bodendiek,C.Rubinos,M.P.Trelles,N.Coleman,D.P.Jenkins,H.Wulff,M.Srinivas,Front Pharmacol 2012,3,106.)的无水CH2Cl2(10mL)溶液,使反应缓慢地(经过3小时)升温至0℃,在0℃下搅拌过夜,然后倒入冰水中。用CH2Cl2萃取水相,合并的有机层用NaHCO3水溶液、盐水洗涤,经Na2SO4干燥,过滤后,通过蒸发除去滤液的溶剂,并将残余物用乙醇重结晶,得到白色固体1j′(2.8g,83%收率)。
1H NMR(400MHz,CDCl3)δ7.99-7.92(m,1H),7.78(d,J=7.5Hz,2H),7.47-7.33(m,4H),7.27-7.20(m,2H),7.12(td,J=7.6,1.5Hz,1H),7.04(d,J=7.5Hz,2H),1.78(s,3H)。13C NMR(101MHz,CDCl3)δ152.40,142.18,141.10,135.11,129.76,128.52,127.42,127.01,126.99,123.89,122.90,120.22,55.75,30.20。
在氩气气氛、-78℃下,向1j′(1.0g,3mmol)的无水THF(10mL)溶液中滴加n-BuLi(1.3mL,2.5M的己烷溶液,1.05当量),将溶液在-78℃下搅拌1h,然后在10分钟内向该锂试剂溶液中滴加PhSiH2Cl(1.5当量),并继续在-78℃下搅拌1小时。然后将混合物温热至室温并搅拌2小时。最后,将反应混合物用饱和NH4Cl溶液淬灭,并用EtOAc萃取,真空浓缩,残余物通过硅胶柱色谱纯化,得到化合物1j,为白色固体,收率为58%(0.63g,1.7mmol)。
1H NMR(600MHz,CDCl3)δ7.94(s,1H),7.68(d,J=7.6Hz,2H),7.50(t,J=7.5Hz,1H),7.28(q,J=7.5Hz,3H),7.23-7.16(m,2H),7.11(q,J=7.1Hz,4H),7.05(d,J=7.5Hz,2H),7.00(d,J=7.1Hz,2H),3.57(s,2H),1.81(s,3H)。13C NMR(151MHz,CDCl3)δ153.74,150.06,140.66,139.54,135.34,132.79,131.90,129.79,128.89,127.71,127.64,127.48,127.39,126.06,124.43,120.35,56.71,30.62。
根据方法B制备,以75%的收率得到化合物1k(0.68g,2.2mmol),为无色油状物(Rf=0.6,石油醚)。
1H NMR(400MHz,CDCl3)δ7.70-7.66(m,1H),7.44(t,J=7.6Hz,2H),7.34-7.23(m,5H),7.22-7.08(m,6H),4.27(s,2H),1.75(s,6H)。13C NMR(151MHz,CDCl3)δ156.76,150.57,139.21,135.60,134.91,133.21,131.63,129.62,129.22,128.13,127.72,127.69,127.29,125.98,125.80,125.21,45.38,32.19。
根据方法C制备,以70%的收率得到化合物11(0.91g,2.8mmol),为白色固体(Rf=0.4,石油醚/乙酸乙酯=20∶1)。
1H NMR(400MHz,CDCl3)δ7.65(dd,J=7.4,1.6Hz,1H),7.52(d,J=8.0Hz,1H),7.43(d,J=8.4Hz,2H),7.37(td,J=7.6,1.6Hz,1H),7.24-7.12(m,1H),6.90(d,J=8.4Hz,2H),5.21(s,2H),3.86(dd,J=5.9,3.8Hz,4H),3.20(dd,J=6.0,3.7Hz,4H),1.45(s,9H)。13CNMR(151MHz,CDCl3)δ157.39,152.00,139.63,136.68,129.73,129.60,125.61,124.85,122.23,114.78,66.79,48.45,37.25,32.20。
根据方法C制备,以62%的收率得到化合物1m(0.58g,1.9mmol),为无色油状物(Rf=0.8,石油醚)。
1H NMR(400MHz,CDCl3)δ7.64(dd,J=7.4,1.6Hz,1H),7.50(s,5H),7.37(td,J=7.7,1.6Hz,1H),7.18(td,J=7.3,1.2Hz,1H),5.21(s,2H),1.44(s,9H),0.26(s,9H)。13CNMR(151MHz,CDCl3)δ157.49,141.97,139.69,134.69,133.74,132.80,129.91,128.83,125.68,124.92,37.24,32.25,-1.25。
根据步骤C制备,以59%的收率得到化合物1n(0.69g,2.4mmol),为无色油状物(Rf=0.6,石油醚)。
1H NMR(400MHz,CDCl3)δ8.05(s,1H),7.86-7.78(m,3H),7.69(dd,J=7.4,1.5Hz,1H),7.56(ddd,J=12.0,8.1,1.2Hz,2H),7.53-7.46(m,2H),7.41(td,J=8.0,1.6Hz,1H),7.20(td,J=7.3,1.2Hz,1H),5.35(s,2H),1.46(s,9H)。13C NMR(151MHz,CDCl3)δ157.62,139.85,136.60,133.87,132.98,131.17,130.87,130.02,128.79,128.06,127.75,127.26,126.65,126.03,125.81,124.99,37.31,32.25。
根据步骤C制备,以48%的收率得到化合物1o(0.54g,1.9mmol),为无色油状物(Rf=0.6,石油醚)。
1H NMR(400MHz,CDCl3)δ7.77(s,1H),7.67(dd,J=7.5,1.6Hz,1H),7.61(d,J=2.2Hz,1H),7.52(t,J=8.2Hz,2H),7.45(dd,J=8.3,1.2Hz,1H),7.39(ddd,J=8.4,7.4,1.5Hz,1H),7.20(td,J=7.3,1.1Hz,1H),6.74(dd,J=2.2,0.9Hz,1H),5.30(s,2H),1.44(s,9H)。13C NMR(151MHz,CDCl3)δ157.53,155.96,144.94,139.79,131.12,129.93,129.30,128.98,127.53,126.72,125.75,124.95,111.34,106.37,37.30,32.24。
根据方法C制备,以43%的收率得到化合物1p(0.5g,1.7mmol),为黄色油状物(Rf=0.4,石油醚/乙酸乙酯=60∶1)。
1H NMR(400MHz,CDCl3)δ7.85(s,1H),7.72(dd,J=7.4,1.5Hz,1H),7.55(d,J=8.0Hz,1H),7.44-7.33(m,3H),7.20(td,J=7.3,1.2Hz,1H),7.06(d,J=3.1Hz,1H),6.49(dd,J=3.1,0.8Hz,1H),5.35(s,2H),3.80(s,3H),1.49(s,9H)。13C NMR(151MHz,CDCl3)δ157.44,139.83,137.49,130.13,129.64,129.11,128.90,128.58,128.01,125.58,124.84,121.73,109.15,101.05,37.31,32.73,32.24。
根据步骤C制备,以77%的收率得到化合物1q(0.76g,3.1mmol),为无色油状物(Rf=0.8,石油醚)。
1H NMR(400MHz,CDCl3)δ7.70(d,J=1.5Hz,1H),7.66(dd,J=4.7,0.8Hz,1H),7.50(d,J=8.0Hz,1H),7.41-7.33(m,2H),7.23-7.17(m,2H),5.34(s,2H),1.46(s,9H)。13C NMR(151MHz,CDCl3)δ157.22,139.40,137.61,132.25,131.31,130.12,128.79,128.39,125.71,125.05,37.24,32.26。
根据方法D制备,以83%的收率得到化合物1r(0.84g,3.3mmol),为无色油状物(Rf=0.8,石油醚)。
1H NMR(400MHz,CDCl3)δ7.55(d,J=7.3Hz,1H),7.47(d,J=8.0Hz,1H),7.35(t,J=7.6Hz,1H),7.23(t,J=7.5Hz,2H),7.14(dt,J=22.7,7.6Hz,4H),4.67(s,2H),2.50(s,2H),1.43(s,9H)。13C NMR(151MHz,CDCl3)δ157.02,139.43,138.58,129.99,129.71,128.42,128.34,125.48,124.83,124.68,37.15,32.10,22.06。
实施例2
乙烯基醚底物的合成
方法E:根据报道的文献改编(Y.Okimoto,S.Sakaguchi,Y.Ishii,J.Am.Chem.Soc.2002,124,1590-1591.)。在氩气保护下,向[Ir(cod)Cl]2(33.6mg,0.05mmol)和Na2CO3(318mg,3.0mmol)的甲苯溶液(5mL)中加入醇(5.0mmol)和乙酸乙烯酯(10.0mmol),反应混合物在100℃下搅拌5h。用水(20mL)淬灭后,混合物用EtOAc(3×10mL)萃取,合并的有机相用无水MgSO4干燥,过滤,减压浓缩,残余物通过硅胶柱色谱纯化,得到所需的乙烯基醚。
根据方法E制备,得到2af,为无色油状物(0.820g,3.56mmol,71%收率)。
1H NMR(600MHz,CDCl3)δ6.47(dd,J=14.3,6.8Hz,1H),4.98(s,1H),4.68(d,J=6.0Hz,1H),4.59(d,J=6.0Hz,1H),4.40(t,J=7.3Hz,1H),4.19(dd,J=14.3,2.3Hz,1H),4.03(dd,J=6.8,2.3Hz,1H),3.72(dd,J=10.0,6.4Hz,1H),3.66(dd,J=10.0,8.1Hz,1H),3.32(s,3H),1.48(s,3H),1.32(s,3H)。13C NMR(151MHz,CDCl3)δ151.32,112.52,109.27,86.95,85.08,84.42,81.93,68.27,54.82,26.40,24.93。
根据方法E制备,得到2ag,为无色油状物(1.0g,3.49mmol,70%收率)。
1H NMR(600MHz,CDCl3)δ6.45(dd,J=14.2,6.7Hz,1H),4.61(dd,J=8.0,2.5Hz,1H),4.38(d,J=2.5Hz,1H),4.26-4.20(m,2H),4.03(dd,J=6.8,2.2Hz,1H),3.93(dt,J=13.0,1.4Hz,1H),3.84(d,J=10.7Hz,1H),3.77(dd,J=17.2,11.9Hz,2H),1.54(s,3H),1.47(s,3H),1.41(s,3H),1.34(s,3H)。13C NMR(151MHz,CDCl3)δ151.89,108.98,108.86,101.97,87.38,70.90,70.11,70.08,69.71,61.09,26.54,25.84,25.23,24.00。
根据步骤E制备,得到2ah,为无色油状物(0.620g,3.40mmol,68%收率)。
1H NMR(400MHz,CDCl3)δ6.32(dd,J=14.1,6.5Hz,1H),4.28(dd,J=14.1,1.4Hz,1H),3.94(dd,J=6.5,1.4Hz,1H),3.52(td,J=10.7,4.3Hz,1H),2.15-2.03(m,2H),1.70-1.61(m,2H),1.37(dddt,J=24.1,12.6,10.4,3.3Hz,2H),1.07-0.94(m,2H),0.91(m,7H),0.77(d,J=7.0Hz,3H)。13C NMR(101MHz,CDCl3)δ151.30,87.49,79.80,47.76,40.87,34.37,31.47,25.80,23.47,22.11,20.73,16.32。
根据步骤E制备,得到2ai,为白色固体(1.49g,3.59mmol,72%收率)。注意:将粗制2ai通过在氧化铝中性物(石油醚)柱色谱纯化。
1H NMR(600MHz,CDCl3)δ6.33(dd,J=14.1,6.5Hz,1H),4.29(d,J=14.1Hz,1H),3.97(d,J=6.4Hz,1H),3.69(tt,J=10.8,4.7Hz,1H),1.96(dt,J=12.7,3.5Hz,1H),1.87(d,J=12.5Hz,1H),1.80(ddt,J=15.3,9.5,4.9Hz,1H),1.74(dt,J=13.1,3.2Hz,1H),1.68-1.62(m,2H),1.57-1.43(m,4H),1.38-1.30(m,5H),1.30-1.21(m,4H),1.11(ddd,J=26.0,14.3,7.8Hz,6H),0.99(tdd,J=22.8,12.7,4.6Hz,4H),0.91-0.84(m,10H),0.81(s,3H),0.65(s,4H)。13C NMR(151MHz,CDCl3)δ150.64,88.07,78.96,56.48,56.28,54.35,44.76,42.59,40.02,39.51,36.82,36.17,35.79,35.60,35.47,34.55,32.06,28.70,28.24,28.00,24.20,23.83,22.81,22.55,21.23,18.66,12.26,12.06。
根据步骤E制备,得到2aj,为白色固体(0.89g,2.85mmol,57%收率)。
1H NMR(400MHz,CDCl3)δ7.21(d,J=8.6Hz,1H),6.72(dd,J=8.6,2.6Hz,1H),6.64(d,J=2.4Hz,1H),6.39(dd,J=14.1,6.5Hz,1H),4.30(d,J=14.1Hz,1H),3.97(d,J=6.5Hz,1H),3.87-3.80(m,1H),3.78(s,3H),2.93-2.77(m,2H),2.30(dq,J=12.8,3.7Hz,1H),2.25-2.08(m,2H),2.02(dt,J=12.5,3.1Hz,1H),1.89(ddt,J=10.9,5.3,2.4Hz,1H),1.73(dddd,J=12.1,9.6,7.1,3.1Hz,1H),1.67-1.56(m,1H),1.54-1.30(m,5H),1.30-1.20(m,1H),0.84(s,3H)。13C NMR(101MHz,CDCl3)δ157.42,151.87,137.90,132.50,126.32,113.76,111.45,88.37,87.78,55.18,49.95,43.84,43.53,38.54,37.45,29.78,27.77,27.23,26.24,23.21,11.73。
根据方法E制备,得到2ak,为白色固体(1.00g,3.13mmol,92%收率)。
1H NMR(600MHz,CDCl3)δ8.00(d,J=8.4Hz,1H),7.63(ddd,J=8.3,6.6,1.6Hz,1H),7.38(dd,J=8.4,1.5Hz,1H),7.36-7.30(m,3H),7.25-7.13(m,2H),6.54(dd,J=14.3,6.8Hz,1H),4.74(s,2H),4.20(dd,J=14.3,2.3Hz,1H),4.06(dd,J=6.9,2.3Hz,1H),2.38(tt,J=8.4,4.8Hz,1H),1.41-1.36(m,2H),1.09(dq,J=6.5,3.6Hz,2H)。13C NMR(151MHz,CDCl3)δ162.60(d,J=247.9Hz),162.56,151.34,147.52(d,J=37.3Hz),132.04(d,J=3.4Hz),131.50,131.44,129.30,128.98,126.39,125.78(d,J=35.8Hz),125.44,115.43,115.29,87.01,64.57,14.39,9.82。19F NMR(376MHz,CDCl3)δ-113.54。
实施例3
对映选择性C-H硅烷化的反应条件优化
反应条件:在氩气保护、1.0mL溶剂中,1a(0.1mmol)、2a(0.22mmol)、[Rh(cod)Cl]2(2mol%)、配体(4mol%)在100℃反应1h。以CHCl2CHCl2作为内标、通过1HNMR确定收率;括号中为分离收率;通过手性HPLC测定ee值。
使用二氢硅烷1a研究未活化的C(sp3)-H键对映选择性硅基化,以[Rh(cod)Cl]2作为催化剂,加入双膦配体,1a可以与苯乙烯2a形成六元金属环中间体。当手性配体是BINAP(L1和L2)、Segphos(L3和L4)和MeOBIPHEP(L5)时,反应在1小时内发生,以61~72%收率、3~33%ee得到环化的二氢苯并噻咯3a和直接氢化硅烷化的副产物4a。这表明对映选择性的脂肪族C-H硅基化/烯烃插入策略对于构建四取代的硅立体异构硅烷是可行的。在没有烯烃的情况下,Rh催化只能得到C-H甲硅烷基化产物,大部分原料二氢硅烷1a在反应中分解。对手性双膦配体进一步筛选,Josiphos配体显著提高了收率和ee值,L7~L9的收率为76~78%,ee值为83~85%。对溶剂的筛选表明,使用DCE(1,2-二氯乙烷)可使ee值提高到92%,而1,4-二氧六环、正己烷的ee与甲苯相近,其他Rh催化剂,例如[Rh(cod)OH]2和[Rh(nbd)Cl]2对反应影响不大。
方法F:在充满氩气的手套箱内,在干燥的5mL微波反应管中装入[Rh(cod)Cl]2(1mg,0.002mmol),((R,Sp)-Josiphos(2.2mg,0.004mmol)和无水DCE(1mL),室温下搅拌5~10分钟后,加入二氢硅烷(0.10mmol)和烯烃(0.22mmol)。将管盖好并从手套箱中取出,所得混合物置于预热的(100℃)铝块中,搅拌1小时。然后将反应混合物浓缩并通过制备TCL纯化,得到目标产物。通过手性HPLC分析确定对映体过量,在相同的条件下用(±)-BINAP或(±)-Josiphos反应得到相应的外消旋体作为对照。
在确定了最佳反应条件后,发明人进行了底物的拓展,芳香环上带有不同官能团(包括吸电子氟、氯和给电子甲氧基、萘基)的二氢硅烷底物,都与苯乙烯顺利反应,以良好的收率(42~74%)、优异对映选择性(90~97%ee)得到不对称四取代的二氢苯并噻咯产物。接着,将两个甲基替换为乙基、环丙甲基、环己基、受保护的羟基和9-芴,对映选择性和收率不受影响,仅一个甲基变为苯基,在良好的对映体控制下以1.3∶1dr值获得非对映异构体。与硅相连的R3可以是官能化的苯环,比如含有氨基、三甲基甲硅烷基,还可以是萘环和杂环,比如苯并呋喃、吲哚、噻吩和苄基,都是合适的底物。最后,各种苯乙烯衍生物,例如2-氟、3-三氟甲基、4-甲氧基、4-氟、4-氯、受保护羟基、4-Bpin取代的苯基,甲氧基取代的吡啶基都是合适的底物,其他类型的烯烃,包括乙烯基醚、乙烯基硅烷、乙烯基锗烷、乙烯基硼烷酯也能顺利转化,这些丰富的官能团为之后的衍生修饰提供了多种可能。为了进一步证明本发明方法的实用性,发明人利用几种生物活性分子、药物和材料的核心结构单元尝试反应,D-核呋喃糖苷、双丙酮果糖、(-)-薄荷醇、脱氢胆固醇、γ-雌二醇、匹伐他汀片段等都可以以良好的收率、优异的立体选择性得到产物。
实施例4
根据方法F,用相应的二氢硅烷(24.0mg,0.1mmol),苯乙烯(22.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3a,为无色油状物(25.7mg,0.075mmol,收率:75%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为92%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=1.0mL/min,温度=28℃,tr(major)=11.6min,tr(minor)=13.0min。[α]D 25.6=-42.30(c=1.0,CHCl3)。
1H NMR(600MHz,CDCl3)δ7.56(d,J=7.0Hz,3H),7.40(d,J=7.3Hz,1H),7.39-7.28(m,4H),7.24(q,J=6.2,5.5Hz,3H),7.14(t,J=7.9Hz,3H),2.87-2.59(m,2H),1.48-1.44(m,2H),1.42(s,3H),1.27(s,3H),1.25(d,J=8.3Hz,1H),1.17(d,J=15.1Hz,1H)。13C NMR(151MHz,CDCl3)δ162.60,144.57,136.90,135.43,134.34,132.93,130.16,129.23,128.30,127.92,127.79,125.93,125.62,123.77,43.73,34.14,33.67,30.17,27.07,16.48。HRMS(EI,m/z)精确质量计算C24H26Si[M+]:342.1798,实测值:342.1800。
实施例5
根据方法F,用相应的二氢硅烷(25.8mg,0.1mmol),苯乙烯(22.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后浓缩反应混合物,并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3b,为无色油状物(25.6mg,0.071mmol,收率:71%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为90%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=1.0mL/min,温度=28℃,tr(minor)=12.5min,tr(major)=14.8min。[α]D 25.4=-37.90(c=1.0,CHCl3)。
1H NMR(600MHz,CDCl3)δ7.54(d,J=6.7Hz,2H),7.36(q,J=7.3,6.6Hz,3H),7.29(dd,J=8.5,4.7Hz,1H),7.27-7.21(m,2H),7.14(t,J=9.6Hz,4H),7.06(td,J=8.7,2.1Hz,1H),2.72(tdd,J=22.8,14.5,8.4Hz,2H),1.46(t,J=8.6Hz,2H),1.40(s,3H),1.28(d,J=15.2Hz,1H),1.25(s,3H),1.19(d,J=15.2Hz,1H)。13C NMR(151MHz,CDCl3)δ161.51(d,J=245.7Hz),157.93(d,J=2.0Hz),144.23,138.10(d,J=4.5Hz),136.17,134.27,129.46,128.34,128.03,127.81,125.75,125.28(d,J=7.4Hz),118.20(d,J=18.6Hz),117.27(d,J=22.6Hz),43.21,34.26,33.84,30.09,27.33,16.26。19F NMR(565MHz,CDCl3)δ-118.43。HRMS(EI,m/z)精确质量计算C24H25FSi[M+]:360.1704,实测值:360.1703。
实施例6
根据方法F,用相应的二氢硅烷(27.5mg,0.1mmol),苯乙烯(22.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3c,为无色油状物(26.1mg,0.069mmol,收率:69%)。使用Chiralpak OD-3进行HPLC分析,对映体过量为90%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=1.0mL/min,温度=28℃,tr(minor)=13.0min,tr(major)=14.8min。[α]D 26.0=-54.20(c=1.0,CHCl3)。
1H NMR(600MHz,CDCl3)δ7.54(d,J=6.7Hz,2H),7.40(s,1H),7.36(dt,J=16.6,8.3Hz,4H),7.26(d,J=8.7Hz,1H),7.24(d,J=6.5Hz,2H),7.16(t,J=7.3Hz,1H),7.12(d,J=7.6Hz,2H),2.72(tdd,J=22.8,14.5,8.4Hz,2H),1.46(t,J=8.6Hz,2H),1.39(s,3H),1.27(d,J=15.3Hz,1H),1.25(s,3H),1.17(d,J=15.2Hz,1H)。13C NMR(151MHz,CDCl3)δ160.75,144.12,138.20,136.00,134.27,132.19,132.06,130.19,129.50,128.34,128.05,127.82,125.79,125.26,43.39,34.05,33.60,30.05,27.06,16.22。HRMS(EI,m/z)精确质量计算C24H25ClSi[M+]:376.1409,实测值:376.1399。
实施例7
根据方法F,用相应的二氢硅烷(27.0mg,0.1mmol),苯乙烯(22.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=60/1),得到产物3d,为无色油状物(27.6mg,0.074mmol,收率:74%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为95%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=99.8∶0.2,流速=1.0mL/min,温度=28℃,tr(minor)=25.7min,tr(major)=32.3min。[α]D 25.5=-57.20(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.63-7.49(m,2H),7.39-7.31(m,3H),7.28-7.20(m,3H),7.14(t,J=6.4Hz,3H),7.03(d,J=2.6Hz,1H),6.97(dd,J=8.5,2.7Hz,1H),3.80(s,3H),2.74(qt,J=14.4,8.1Hz,2H),1.50-1.42(m,2H),1.40(s,3H),1.28-1.22(m,4H),1.17(d,J=15.2Hz,1H)。13C NMR(151MHz,CDCl3)δ157.83,154.88,144.52,136.87,136.80,134.36,129.27,128.30,127.93,127.81,125.64,124.72,116.73,116.48,55.35,42.96,34.33,33.91,30.17,27.43,16.38。HRMS(EI,m/z)精确质量计算C25H28OSi[M+]:372.1904,实测值:372.1916。
实施例8
根据方法F,用相应的二氢硅烷(29.0mg,0.1mmol),苯乙烯(22.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3e,为无色油状物(16.6mg,0.042mmol,收率:42%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为97%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=99.5∶0.5,流速=1.0mL/min,温度=28℃,tr(major)=10.2min,tr(minor)=10.6min。[α]D 27.8=-79.10(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.93(d,J=8.5Hz,1H),7.87(dd,J=7.2,2.1Hz,1H),7.80(dd,J=7.8,1.5Hz,1H),7.59(dd,J=7.7,1.7Hz,2H),7.54(d,J=8.6Hz,1H),7.47-7.38(m,2H),7.39-7.29(m,3H),7.26-7.20(m,2H),7.20-7.07(m,3H),2.87-2.63(m,2H),1.76-1.67(m,2H),1.52(s,3H),1.41(s,3H),1.34(s,2H)。13C NMR(101MHz,CDCl3)δ162.35,144.65,137.14,136.41,134.50,132.39,132.16,131.17,129.30,128.83,128.33,128.29,127.99,127.76,126.34,125.61,125.13,122.81,44.09,34.14,33.62,30.53,27.02,16.45。HRMS(EI,m/z)精确质量计算C28H28Si[M+]:392.1955,实测值:392.1957。
实施例9
根据方法F,用相应的二氢硅烷(26.9mg,0.1mmol),苯乙烯(22.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3f,为无色油状物(25.5mg,0.069mmol,收率:69%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为92%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=0.7mL/min,温度=28℃,tr(major)=15.2min,tr(minor)=15.8min。[α]D 26.0=-62.00(c=1.0,CHCl3)。
H NMR(600MHz,CDCl3)δ7.57(td,J=7.7,7.2,1.9Hz,3H),7.40(td,J=7.6,1.4Hz,1H),7.38-7.32(m,3H),7.23(d,J=7.3Hz,4H),7.19-7.08(m,3H),2.82-2.65(m,2H),1.72(q,J=7.3Hz,2H),1.60(ddt,J=20.6,13.9,7.0Hz,2H),1.47-1.40(m,2H),1.11(d,J=3.4Hz,2H),0.78(t,J=7.4Hz,3H),0.60(t,J=7.4Hz,3H)。13C NMR(151MHz,CDCl3)δ159.67,144.71,137.47,137.10,134.35,132.91,129.74,129.13,128.30,127.87,127.76,125.81,125.59,124.95,51.52,36.18,35.65,30.22,19.12,16.84,9.20。HRMS(EI,m/z)精确质量计算C24H25Si[(M-Et)+]:341.1720,实测值:341.1721。
实施例10
根据方法F,用相应的二氢硅烷(32.1mg,0.1mmol),苯乙烯(22.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3g,为无色油状物(30.4mg,0.070mmol,收率:70%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为91%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=1.0mL/min,温度=28℃,tr(major)=11.9min,tr(minor)=14.3min。[α]D 25.4=-42.60(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.58(ddd,J=7.5,5.1,2.0Hz,3H),7.44-7.30(m,5H),7.23(t,J=3.8Hz,3H),7.15(dt,J=7.3,2.9Hz,3H),2.87-2.63(m,2H),1.92(dd,J=13.9,4.9Hz,1H),1.71(dd,J=13.9,5.5Hz,1H),1.56-1.38(m,6H),0.52(dddd,J=12.8,7.9,4.9,3.0Hz,1H),0.43(tdd,J=8.7,5.4,4.0Hz,1H),0.32(tddd,J=12.9,7.7,4.4,1.9Hz,2H),0.19-0.04(m,3H),-0.05(dq,J=9.4,5.0Hz,1H),-0.16(dtd,J=9.9,4.9,4.0,2.6Hz,1H),-0.20--0.30(m,1H)。13C NMR(101MHz,CDCl3)δ160.53,144.77,137.30,137.22,134.35,132.92,129.60,129.09,128.30,127.81,127.75,125.83,125.58,125.18,52.82,49.27,48.60,30.25,19.64,16.92,7.14,7.09,6.23,5.74,4.16,4.03。HRMS(EI,m/z)精确质量计算C26H27Si[(M-C4H7)+]:367.1877,实测值:367.1872。
实施例11
根据方法F,与相应的二氢硅烷(28.1mg,0.1mmol),苯乙烯(22.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3h,为无色油状物(26.3mg,0.069mmol,收率:69%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为85%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=1.0mL/min,温度=28℃,tr(major)=17.1min,tr(minor)=19.1min。[α]D 26.1=-35.90(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.62-7.49(m,3H),7.46-7.40(m,2H),7.34(dd,J=5.7,1.6Hz,3H),7.27-7.21(m,3H),7.15(td,J=5.7,5.2,2.2Hz,3H),2.81-2.62(m,2H),1.83-1.52(m,8H),1.49-1.42(m,2H),1.39(dt,J=12.1,2.2Hz,1H),1.32-1.23(m,2H),1.11(d,J=15.4Hz,1H)。13C NMR(101MHz,CDCl3)δ163.38,144.62,137.11,136.02,134.28,132.95,130.09,129.22,128.30,127.91,127.78,126.16,125.61,124.25,48.16,41.04,40.99,30.17,26.07,23.13,23.10,19.92,16.54。HRMS(EI,m/z)精确质量计算C27H30Si[M+]:382.2111,实测值:382.2114。
实施例12
根据方法F,用相应的二氢硅烷(45.3mg,0.1mmol),苯乙烯(22.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=60/1),得到产物3i,为无色油状物(37.3mg,0.067mmol,收率:67%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为91%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=95∶5,流速=1.0mL/min,温度=28℃,tr(minor)=6.9min,tr(major)=11.1min。[α]D 25.7=-66.40(c=1.0,CHCl3)。
1H NMR(600MHz,CDCl3)δ7.62(d,J=7.3Hz,1H),7.59-7.53(m,2H),7.45(t,J=7.3Hz,1H),7.40(dd,J=7.7,3.6Hz,2H),7.36(t,J=7.3Hz,2H),7.31(t,J=7.1Hz,1H),7.24-7.19(m,4H),7.14(d,J=7.4Hz,1H),7.12-7.05(m,4H),6.90(t,J=7.3Hz,1H),6.81(dd,J=17.9,7.8Hz,3H),6.40(d,J=8.1Hz,2H),4.00(td,J=8.7,6.0Hz,1H),3.90(td,J=8.7,5.9Hz,1H),3.62(td,J=9.4,5.5Hz,1H),3.41(td,J=9.3,5.6Hz,1H),2.82-2.63(m,2H),2.41-2.30(m,2H),2.26-2.13(m,2H),1.48-1.41(m,3H),1.38(d,J=15.8Hz,1H)。13C NMR(151MHz,CDCl3)δ158.74,158.59,157.89,144.15,136.60,136.25,134.78,134.27,133.28,130.57,129.41,129.15,128.32,128.20,127.74,126.69,125.70,124.76,120.61,120.29,114.42,114.16,65.03,65.01,48.21,43.63,43.27,30.04,20.56,16.89。HRMS(DART,m/z)精确质量计算C38H39O2Si[(M+H)+]:555.2714,实测值:555.2711。
实施例13
根据方法F,用相应的二氢硅烷(36.3mg,0.1mmol),1-甲氧基-4-乙烯基苯(29.5mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3j,为无色油状物(35.0mg,0.071mmol,收率:71%)。使用ChiralpakAD-3柱进行HPLC分析,对映体过量为90%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=99∶1,流速=1.0mL/min,温度=28℃,tr(major)=7.0min,tr(minor)=12.4min。[α]D 26.8=-62.40(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.75(d,J=7.5Hz,1H),7.74-7.68(m,4H),7.43(qd,J=4.6,1.7Hz,3H),7.34(td,J=7.4,1.0Hz,1H),7.29-7.20(m,3H),7.16(d,J=7.5Hz,1H),7.14-7.07(m,3H),6.98(td,J=7.5,1.0Hz,1H),6.83-6.77(m,2H),6.73(d,J=7.6Hz,1H),6.36(dt,J=7.9,0.9Hz,1H),3.77(s,3H),2.93-2.74(m,2H),1.84(d,J=1.8Hz,2H),1.67-1.60(m,2H)。13C NMR(151MHz,CDCl3)δ157.74,157.06,156.18,155.82,139.77,138.94,136.52,136.47,136.38,134.49,132.78,130.59,129.57,128.70,128.14,127.93,127.71,127.00,126.75,126.70,125.93,124.21,123.82,119.72,119.64,113.80,62.30,55.25,29.36,23.11,17.59。HRMS(EI,m/z)精确质量计算C35H30OSi[M+]:494.2060,实测值:494.2065。
实施例14
根据方法F,用相应的二氢硅烷(30.3mg,0.1mmol),(乙烯基氧基)环己烷(27.8mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=50/1),得到产物3k,为无色油状物(33.2mg,0.078mmol,收率:78%)。通过1H NMR分析,非对映异构体比例确定为1.3∶1,使用Chiralpak OD-3柱进行HPLC分析,对映体过量分别为94%ee和85%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=99∶1,流速=1.0mL/min,温度=28℃,主要产物:tr(major)=4.6min,tr(minor)=6.2min,次要产品:tr(major)=3.8min,tr(minor)=4.0min。[α]D 24.4=-22.10(c=1.0,CHCl3)。
1H NMR(600MHz,CDCl3)δ7.71(dd,J=27.0,7.2Hz,1H),7.64-7.52(m,2H),7.40-7.27(m,6H),7.25-7.10(m,4H),7.01(dd,J=7.7,3.0Hz,1H),3.73-3.46(m,2H),3.14(dtt,J=55.0,8.8,3.9Hz,1H),1.89-1.79(m,3H),1.75-1.68(m,3H),1.67-1.57(m,4H),1.52(dd,J=9.1,3.5Hz,1H),1.46(ddd,J=8.2,6.9,4.1Hz,1H),1.26-1.12(m,5H)。13C NMR(151MHz,CDCl3)δ161.89,161.78,152.52,152.35,136.63,136.32,136.22,136.14,134.38,134.35,132.89,132.80,130.10,130.07,129.25,129.19,127.94,127.85(twocarbons),127.76,126.85,126.78,126.48,126.45,126.13,126.10,125.46,125.33,64.18,64.03,51.75,51.56,32.50,32.32(两个碳原子),32.28,32.24,32.16,31.18,30.90,25.83,24.18,16.85,16.48。HRMS(EI,m/z)精确质量计算C29H34OSi[M+]:426.2373,实测值:426.2376。
实施例15
根据方法F,用相应的二氢硅烷(32.6mg,0.1mmol),苯乙烯(22.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=10/1),得到产物31,为无色油状物(33.0mg,0.077mmol,收率:77%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为95%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=99.3∶0.7,流速=1.0mL/min,温度=28℃,tr(major)=8.3min,tr(minor)=9.3min。[α]D 24.9=-45.2(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.54(d,J=7.1Hz,1H),7.46(d,J=8.6Hz,2H),7.42-7.33(m,2H),7.27-7.20(m,3H),7.15(dd,J=7.3,3.1Hz,3H),6.89(d,J=8.6Hz,2H),3.87-3.81(m,4H),3.22-3.15(m,4H),2.83-2.63(m,2H),1.47-1.42(m,2H),1.41(s,3H),1.28(s,3H),1.21(d,J=15.1Hz,1H),1.13(d,J=15.1Hz,1H)。13C NMR(101MHz,CDCl3)δ162.52,151.80,144.75,135.96,135.57,132.89,129.99,128.27,127.78,125.98,125.84,125.56,123.69,114.74,66.83,48.51,43.66,34.16,33.69,30.23,27.34,16.59。HRMS(EI,m/z)精确质量计算C28H33ONSi[M+]:427.2326,实测值:427.2322。
实施例16
根据方法F,用相应的二氢硅烷(31.3mg,0.1mmol),苯乙烯(22.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和((R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3m,为无色油状物(31.4mg,0.076mmol,收率:76%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为94%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=1.0mL/min,温度=28℃,tr(major)=7.5min,tr(minor)=9.3min。[α]D 25.4=-38.10(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.59-7.52(m,3H),7.50(d,J=7.9Hz,2H),7.41-7.34(m,2H),7.25-7.20(m,3H),7.15(dd,J=7.3,3.1Hz,3H),2.92-2.56(m,2H),1.49-1.44(m,2H),1.42(s,3H),1.28(s,3H),1.25(d,J=6.0Hz,1H),1.16(d,J=15.2Hz,1H),0.25(s,9H)。13CNMR(101MHz,CDCl3)δ162.59,144.61,141.60,137.32,135.44,133.58,132.92,132.75,130.14,128.30,127.78,125.93,125.61,123.77,43.75,34.17,33.74,30.19,26.96,16.39,-1.23。HRMS(EI,m/z)精确质量计算C27H34Si2[M+]:414.2194,实测值:414.2200。
实施例17
根据方法F,用相应的二氢硅烷(29.1mg,0.1mmol),苯乙烯(22.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3n,为无色油状物(26.0mg,0.066mmol,收率:66%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为93%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=1.0mL/min,温度=28℃,tr(minor)=45.2min,tr(major)=56.4min。[α]D 25.5=-46.40(c=1.0,CHCl3)。
1H NMR(600MHz,CDCl3)δ8.05(s,1H),7.80(dd,J=7.5,3.2Hz,3H),7.71-7.56(m,2H),7.49-7.41(m,3H),7.39(d,J=7.9Hz,1H),7.27(t,J=7.2Hz,1H),7.23(t,J=7.6Hz,2H),7.14(d,J=7.6Hz,3H),2.76(dtd,J=31.3,14.8,7.2Hz,2H),1.57-1.51(m,2H),1.45(s,3H),1.33(d,J=15.1Hz,1H),1.28(s,3H),1.22(d,J=15.1Hz,1H)。13C NMR(151MHz,CDCl3)δ162.68,144.53,135.37,135.19,134.35,133.78,133.04,132.93,130.37,130.24,128.32,128.09,127.82,127.71,127.18,126.48,126.00,125.96,125.65,123.82,43.80,34.19,33.64,30.23,27.24,16.58。HRMS(EI,m/z)精确质量计算C28H28Si[M+]:392.1955,实测值:392.1970。
实施例18
根据方法F,用相应的二氢硅烷(28.0mg,0.1mmol),(乙烯基氧基)环己烷(27.8mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=40/1),得到产物3o,为无色油状物(27.6mg,0.068mmol,收率:68%)。使用ChiralpakOD-3柱进行HPLC分析,对映体过量为94%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=1.0mL/min,温度=28℃,tr(minor)=11.8min,tr(major)=14.2min。[α]D 26.0=-42.30(c=1.0,CHCl3)。
1H NMR(600MHz,CDCl3)δ7.83(s,1H),7.68(d,J=7.1Hz,1H),7.60(d,J=2.2Hz,1H),7.51(s,2H),7.45-7.41(m,1H),7.38(d,J=7.8Hz,1H),7.30-7.27(m,1H),6.74(d,J=2.1Hz,1H),3.62(dtd,J=19.9,9.1,6.8Hz,2H),3.15(td,J=9.1,3.8Hz,1H),1.90-1.81(m,2H),1.73-1.66(m,2H),1.57-1.50(m,3H),1.45(s,3H),1.30(d,J=10.6Hz,2H),1.27(s,3H),1.25-1.13(m,5H)。13C NMR(151MHz,CDCl3)δ162.51,155.75,144.78,135.80,133.08,130.34,130.14,130.09,127.77,127.28,125.89,123.71,111.08,106.38,64.24,43.71,34.12,33.63,32.35,32.29,28.07,25.82,24.18,17.11。HRMS(EI,m/z)精确质量计算C26H32O2Si[M+]:404.2166,实测值:404.2165。
实施例19
根据方法F,用相应的二氢硅烷(29.4mg,0.1mmol),苯乙烯(22.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=30/1),得到产物3p,为无色油状物(25.0mg,0.063mmol,收率:63%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为95%ee。HPLC条件波长=220nm,洗脱液:正己烷/异丙醇=99∶1,流速=1.0mL/min,温度=28℃,tr(minor)=5.9min,tr(major)=6.6min。[α]D 26.0=-49.60(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.89(s,1H),7.64(d,J=7.1Hz,1H),7.48-7.39(m,3H),7.36(d,J=8.2Hz,1H),7.31-7.24(m,4H),7.19(d,J=7.7Hz,3H),7.06(d,J=3.1Hz,1H),6.50(dd,J=3.1,0.9Hz,1H),3.80(s,3H),2.79(qdd,J=14.4,10.6,6.5Hz,2H),1.53(ddd,J=10.2,6.9,3.0Hz,2H),1.47(s,3H),1.35-1.30(m,4H),1.23(d,J=15.1Hz,1H)。13C NMR(151MHz,CDCl3)δ162.58,144.95,137.39,136.44,133.07,129.91,128.84,128.51,128.25,127.81,127.08,125.82,125.50,125.36,123.68,109.06,101.08,43.70,34.24,33.70,32.72,30.33,27.72,16.98。HRMS(ESI,m/z)精确质量计算C27H30NSi[(M+H)+]:396.2142,实测值:396.2139。
实施例20
根据方法F,用相应的二氢硅烷(24.6mg,0.1mmol)、(乙烯基氧基)环己烷(27.8mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=40/1),得到产物3q,为无色油状物(17.3mg,0.047mmol,收率:47%)。使用ChiralpakOD-3柱进行HPLC分析,对映体过量为55%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=0.5mL/min,温度=28℃,tr(minor)=19.2min,tr(major)=21.4min。[α]D 25.9=-30.30(c=1.0,CHCl3)。
1H NMR(600MHz,CDCl3)δ7.71-7.55(m,2H),7.46-7.38(m,1H),7.36(d,J=7.8Hz,1H),7.34-7.30(m,1H),7.24(d,J=7.2Hz,1H),7.18(dd,J=4.5,3.4Hz,1H),3.71-3.60(m,2H),3.19(tt,J=9.1,3.9Hz,1H),1.91-1.81(m,2H),1.76-1.66(m,2H),1.52(t,J=7.8Hz,3H),1.43(s,3H),1.32(s,3H),1.30(d,J=7.6Hz,2H),1.27-1.18(m,5H)。13C NMR(151MHz,CDCl3)δ162.23,135.96,135.81,135.36,132.87,131.42,130.30,128.15,125.95,123.69,64.00,43.71,34.09,33.70,32.34,32.27,28.48,25.84,24.21,17.71。HRMS(EI,m/z)精确质量计算C22H30OSSi[M+]:370.1781,实测值:370.1790。
实施例21
根据方法F,用相应的二氢硅烷(25.4mg,0.1mmol),苯乙烯(22.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和((R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3r,为无色油状物(24.9mg,0.070mmol,收率:70%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为80%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=1.0mL/min,温度=28℃,tr(major)=17.4min,tr(minor)=19.8min。[α]D 25.1=-10.40(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.39(t,J=7.3Hz,2H),7.32(dt,J=7.3,1.2Hz,1H),7.27-7.15(m,6H),7.15-7.06(m,3H),7.06-6.98(m,2H),2.71-2.56(m,2H),2.47-2.38(m,2H),1.36(s,3H),1.23(s,3H),1.20-1.13(m,2H),1.03(d,J=15.2Hz,1H),0.96(d,J=15.2Hz,1H)。13C NMR(101MHz,CDCl3)δ162.19,144.61,139.28,135.80,132.73,130.00,128.31,127.77,125.66,125.61,124.32,123.69,43.42,34.07,33.86,30.09,25.65,24.67,15.78。HRMS(EI,m/z)精确质量计算C18H21Si[(M-Bn)+]:265.1407,实测值:265.1414。
实施例22
根据方法F,用相应的二氢硅烷(27.0mg,0.1mmol),1-氟-2-乙烯基苯(26.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=60/1),得到产物3s,为无色油状物(26.2mg,0.067mmol,收率:67%)。使用ChiralpakOD-3柱进行HPLC分析,对映体过量为94%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=1.0mL/min,温度=28℃,tr(minor)=16.4min,tr(major)=20.2min。[α]D 26.1=-59.20(c=1.0,CHCl3)。
1H NMR(600MHz,CDCl3)δ7.57(d,J=6.5Hz,2H),7.42-7.30(m,3H),7.28(dd,J=8.6,2.1Hz,1H),7.17-7.07(m,2H),7.04(d,J=2.6Hz,1H),7.03-6.86(m,3H),3.80(s,3H),2.75(qt,J=14.9,8.3Hz,2H),1.45(t,J=8.9Hz,2H),1.41(s,3H),1.26(s,4H),1.20(d,J=15.1Hz,1H)。13C NMR(151MHz,CDCl3)δ160.91(d,J=244.4Hz),157.86,154.88,136.68(d,J=16.2Hz),134.36,131.36(d,J=15.7Hz),129.82(d,J=5.2Hz),129.30,127.94,127.30(d,J=8.0Hz),124.72,123.88(d,J=3.3Hz),116.83,116.37,115.16,115.01,55.33,42.97,34.35,33.88,27.33,23.68(d,J=3.0Hz),15.09。19F NMR(565MHz,CDCl3)δ-118.90。HRMS(EI,m/z)精确质量计算C25H27FOSi[M+]:390.1810,实测值:390.1821。
实施例23
根据方法F,用相应的二氢硅烷(24.0mg,0.1mmol),1-(三氟甲基)-3-乙烯基苯(37.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1小时。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3t,为无色油状物(32.1mg,0.078mmol,收率:78%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为87%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=1.0mL/min,温度=28℃,tr(major)=9.2min,tr(minor)=9.8min。[α]D 24.3=-43.5(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.62-7.51(m,3H),7.45-7.22(m,10H),2.89-2.67(m,2H),1.49-1.44(m,2H),1.43(s,3H),1.30-1.23(m,4H),1.16(d,J=15.2Hz,1H)。13C NMR(151MHz,CDCl3)δ162.60,145.32,136.54,135.05,134.28,132.85,131.27,130.54(d,J=32.2Hz),130.29,129.37,128.66,128.00,126.01,124.53(q,J=3.3Hz),124.24(d,J=272.1Hz),123.86,122.53(q,J=3.9Hz),43.76,34.17,33.61,30.09,26.99,16.33。19F NMR(376MHz,CDCl3)δ-62.50。HRMS(EI,m/z)精确质量计算C25H25F3Si[M+]:410.1672,实测值:410.1676。
实施例24
根据方法F,用相应的二氢硅烷(24.0mg,0.1mmol),1-甲氧基-4-乙烯基苯(29.5mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=60/1),得到产物3u,为无色油状物(28.2mg,0.076mmol,收率:76%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为95%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=99∶1,流速=1.0mL/min,温度=28℃,tr(minor)=5.5min,tr(major)=6.1min。[α]D 24.5=-55.20(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.64-7.52(m,3H),7.46-7.31(m,5H),7.30-7.22(m,1H),7.07(d,J=8.6Hz,2H),6.80(d,J=8.6Hz,2H),3.79(s,3H),2.81-2.60(m,2H),1.51-1.41(m,5H),1.27(d,J=12.8Hz,4H),1.18(d,J=15.1Hz,1H)。13C NMR(101MHz,CDCl3)δ162.58,157.63,136.98,136.68,135.50,134.34,132.94,130.12,129.20,128.66,127.89,125.91,123.75,113.71,55.26,43.73,34.13,33.67,29.25,27.08,16.72。HRMS(EI,m/z)精确质量计算C25H28OSi[M+]:372.1904,实测值:372.1911。
实施例25
根据方法F,用相应的二氢硅烷(24.0mg,0.1mmol),1-氟-4-乙烯基苯(26.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3v,为无色油状物(28.4mg,0.079mmol,收率:79%)。使用ChiralpakOD-3柱进行HPLC分析,对映体过量为95%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=1.0mL/min,温度=28℃,tr(major)=18.2min,tr(minor)=21.3min。[α]D 26.1=-49.70(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.65-7.51(m,3H),7.49-7.29(m,5H),7.26(td,J=6.8,1.2Hz,1H),7.16-7.02(m,2H),7.00-6.81(m,2H),2.85-2.59(m,2H),1.49-1.38(m,5H),1.26(d,J=9.8Hz,4H),1.16(d,J=15.1Hz,1H)。13C NMR(101MHz,CDCl3)δ162.59,161.11(d,J=243.1Hz),140.08(d,J=3.0Hz),136.78,135.29,134.30,132.89,130.20,129.28,129.10(d,J=7.6Hz),127.94,125.95,123.80,114.94(d,J=21.1Hz),43.74,34.15,33.64,29.42,27.05,16.69。19F NMR(376MHz,CDCl3)δ-118.08。HRMS(EI,m/z)精确质量计算C24H25FSi[M+]:360.1704,实测值:360.1708。
实施例26
根据方法F,用相应的二氢硅烷(24.0mg,0.1mmol),1-氯-4-乙烯基苯(30.5mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3w,为无色油状物(28.0mg,0.074mmol,收率:74%)。使用ChiralpakOD-3柱进行HPLC分析,对映体过量为93%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=99.5∶0.5,流速=1.0mL/min,温度=28℃,tr(major)=21.0min,tr(minor)=31.1min。[α]D 24.4=-45.50(c=1.0,CHCl3)。
1H NMR(600MHz,CDCl3)δ7.55(d,J=6.9Hz,3H),7.41(t,J=7.7Hz,1H),7.35(t,J=8.7Hz,4H),7.27-7.21(m,1H),7.18(d,J=8.0Hz,2H),7.04(d,J=7.9Hz,2H),2.69(dtd,J=31.9,15.0,7.6Hz,2H),1.42(s,5H),1.25(d,J=8.9Hz,4H),1.16(d,J=15.1Hz,1H)。13CNMR(151MHz,CDCl3)δ162.59,142.94,136.68,135.18,134.28,132.87,131.26,130.23,129.30,129.16,128.32,127.96,125.97,123.81,43.74,34.16,33.63,29.61,27.04,16.49。HRMS(DART,m/z)精确质量计算C24H26ClSi[(M+H)+]:377.1487,实测值:377.1483。
实施例27
根据方法F,与相应的二氢硅烷(24.0mg,0.1mmol),2,2-二氟-5-乙烯基苯并[d][1,3]二恶唑(40.5mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=60/1),得到产物3x,为无色油状物(30.1mg,0.071mmol,收率:71%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为94%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=1.0mL/min,温度=28℃,tr(major)=16.2min,tr(minor)=24.4min。[α]D 24.4=-47.90(c=1.0,CHCl3)。
1H NMR(600MHz,CDCl3)δ7.56(dt,J=7.7,2.0Hz,3H),7.43(td,J=7.6,1.4Hz,1H),7.41-7.32(m,4H),7.28-7.24(m,1H),6.89(d,J=8.2Hz,1H),6.86-6.74(m,2H),2.73(dddd,J=45.0,14.5,10.5,6.8Hz,2H),1.47-1.40(m,5H),1.30-1.25(m,4H),1.17(d,J=15.2Hz,1H)。13C NMR(151MHz,CDCl3)δ162.59,143.72,141.75,140.69,136.58,135.05,134.25,132.84,131.60(t,J=254.0Hz),130.29,129.36,127.98,125.98,123.85,122.52,109.08,108.97,43.76,34.19,33.59,30.15,27.00,16.88。19F NMR(565MHz,CDCl3)δ-50.10。HRMS(EI,m/z)精确质量计算C25H24O2F2Si[M+]:422.1508,实测值:422.1502。
实施例28
根据方法F,用相应的二氢硅烷(27.0mg,0.1mmol),4,4,5,5-四甲基-2-(4-乙烯基苯基)-1,3,2-二氧杂硼烷(50.6mg,0.22),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=10/1),得到产物3y,为无色油状物(28.5mg,0.077mmol,收率:77%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为93%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=99∶1,流速=1.0mL/min,温度=28℃,tr(major)=4.6min,tr(minor)=5.4min。[α]D 24.4=-45.8(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.80-7.64(m,2H),7.62-7.51(m,2H),7.45-7.32(m,3H),7.29(d,J=8.5Hz,1H),7.22-7.09(m,2H),7.02(d,J=2.6Hz,1H),6.98(dd,J=8.5,2.7Hz,1H),3.81(s,3H),2.85-2.65(m,2H),1.50-1.43(m,2H),1.42(s,3H),1.34(s,12H),1.26(s,4H),1.20(d,J=15.2Hz,1H)。13C NMR(101MHz,CDCl3)δ157.83,154.88,148.01,136.78,136.74,134.90,134.35,129.27,127.94,127.29,124.72,116.79,116.42,83.60,55.36,42.96,34.34,33.89,30.42,27.44,24.83,16.27。HRMS(EI,m/z)精确质量计算C31H39[11B]O3Si[M+]:498.2756,实测值:498.2773。
实施例29
根据方法F,用相应的二氢硅烷(24.0mg,0.1mmol),2-甲氧基-5-乙烯基吡啶(29.7mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=15/1),得到产物3z,为无色油状物(28.1mg,0.075mmol,收率:75%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为94%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=99.5∶0.5,流速=1.0mL/min,温度=28℃,tr(major)=21.9min,tr(minor)=26.5min。[α]D 25.6=-55.10(c=1.0,CHCl3)。
1H NMR(600MHz,CDCl3)δ7.91(d,J=2.5Hz,1H),7.57(ddd,J=9.5,7.2,1.6Hz,3H),7.43(td,J=7.6,1.4Hz,1H),7.36(tdd,J=8.5,6.4,3.3Hz,5H),7.28-7.24(m,2H),6.64(d,J=8.4Hz,1H),3.91(s,3H),2.73-2.59(m,2H),1.47-1.39(m,5H),1.30-1.26(m,4H),1.18(d,J=15.1Hz,1H)。13C NMR(151MHz,CDCl3)δ162.58,162.54,145.42,138.44,136.63,135.15,134.27,132.87,132.28,130.25,129.31,127.97,125.98,123.83,110.36,53.29,43.76,34.16,33.61,27.04,26.52,16.55。HRMS(ESI,m/z)精确质量计算C24H28NOSi[(M+H)+]:374.1935,实测值:374.1934。
实施例30
根据方法F,用相应的二氢硅烷(24.0mg,0.1mmol),(乙烯基氧基)环己烷(27.8mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3aa,为无色油状物(26.9mg,0.074mmol,收率:74%)。使用ChiralpakOD-3柱进行HPLC分析,对映体过量为91%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=1.0mL/min,温度=28℃,tr(minor)=7.7min,tr(major)=8.6min。[α]D 25.3=-44.10(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.62(dt,J=7.2,1.0Hz,1H),7.60-7.52(m,2H),7.39(ddd,J=8.3,7.0,1.4Hz,1H),7.37-7.27(m,4H),7.26-7.21(m,1H),3.66-3.51(m,2H),3.13(tq,J=8.7,3.8Hz,1H),1.90-1.76(m,2H),1.68(dt,J=9.7,3.3Hz,2H),1.52-1.44(m,3H),1.42(s,3H),1.31-1.06(m,10H)。13C NMR(101MHz,CDCl3)δ162.48,136.89,135.50,134.33,133.05,130.07,129.10,127.76,125.85,123.67,64.16,43.68,34.06,33.65,32.33,32.27,27.64,25.82,24.18,16.76。HRMS(EI,m/z)精确质量计算C24H32OSi[M+]:364.2217,实测值:364.2208。
实施例31
根据方法F,用相应的二氢硅烷(27.0mg,0.1mmol),二甲基(苯基)(乙烯基)硅烷(35.7mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=60/1),得到产物3ab,为无色油状物(30.9mg,0.072mmol,收率:72%)。使用Chiralpak AD-3柱进行HPLC分析,对映体过量为89%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=1.0mL/min,温度=28℃,tr(minor)=5.5min,tr(major)=6.8min。[α]D 26.0=-52.10(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.55-7.39(m,4H),7.31(ddt,J=5.6,3.8,2.1Hz,6H),7.22(d,J=14.3Hz,1H),7.03(d,J=2.7Hz,1H),6.94(dd,J=8.5,2.7Hz,1H),3.78(s,3H),1.36(s,3H),1.21(d,J=18.0Hz,4H),1.15(d,J=15.1Hz,1H),1.02-0.91(m,2H),0.84-0.66(m,2H),0.23(d,J=4.2Hz,6H)。13C NMR(101MHz,CDCl3)δ157.75,154.93,139.01,137.19,137.03,134.41,133.65,129.13,128.82,127.83,127.70,124.64,116.56,116.49,55.31,42.82,34.33,33.92,27.04,8.22,6.45,-3.48,-3.72。HRMS(EI,m/z)精确质量计算C27H34O8i2[M+]:430.2143,实测值:430.2151。
实施例32
根据方法F,用相应的二氢硅烷(27.0mg,0.1mmol),三乙氧基(乙烯基)硅烷(41.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos在无水DCE(1.0mL)、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=60/1),得到产物3ac,为无色油状物(32.1mg,0.075mmol,收率:75%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为89%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=0.5mL/min,温度=28℃,tr(minor)=14.3min,tr(major)=16.1min。[α]D 26.8=-34.10(c=1.0,CHCl3)。
1H NMR(600MHz,CDCl3)δ7.59(d,J=7.1Hz,1H),7.57-7.53(m,2H),7.42-7.38(m,1H),7.34(dq,J=8.6,6.7,5.8Hz,4H),7.23(td,J=7.1,1.1Hz,1H),3.79(q,J=7.0Hz,6H),1.43(s,3H),1.28(s,3H),1.26-1.22(m,2H),1.20(t,J=7.0Hz,9H),1.15-1.06(m,2H),0.66(dddd,J=49.8,15.4,13.1,4.6Hz,2H)。13C NMR(151MHz,CDCl3)δ162.69,136.99,135.48,134.41,132.90,130.06,129.12,127.82,125.82,123.71,58.40,43.60,34.17,33.69,26.62,18.28,5.56,3.01。HRMS(EI,m/z)精确质量计算C24H36O3Si2[M+]:428.2197,实测值:428.2197。
实施例33
根据方法F,用相应的二氢硅烷(27.0mg,0.1mmol),三乙基(乙烯基)锗烷(41.1mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3ad,为无色油状物(33.3mg,0.073mmol,收率:73%)。使用ChiralpakAD-H柱进行HPLC分析,对映体过量为93%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=0.5mL/min,温度=28℃,tr(minor)=8.3min,tr(major)=9.7min。[α]D 26.0=-43.00(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.64-7.50(m,2H),7.41-7.31(m,3H),7.29(d,J=8.5Hz,1H),7.08(d,J=2.7Hz,1H),6.97(dd,J=8.6,2.7Hz,1H),3.82(s,3H),1.41(s,3H),1.30-1.22(m,5H),1.10-1.04(m,2H),0.99(t,J=7.9Hz,9H),0.85-0.65(m,8H)。13C NMR(101MHz,CDCl3)δ157.75,154.94,137.35,137.28,134.40,129.10,127.83,124.62,116.57,116.47,55.31,42.84,34.32,33.97,27.03,8.99,8.10,4.05,3.43。HRMS(EI,m/z)精确质量计算C23H33GeOSi[(M-Et)+]:423.1538,实测值:423.1539。
实施例34
根据方法F,用相应的二氢硅烷(36.3mg,0.1mmol),4,4,5,5-四甲基-2-乙烯基-1,3,2-二氧杂硼烷(33.9mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=30/1),得到产物3ae,为无色油状物(33.3mg,0.065mmol,收率:65%)。使用ChiralpakAD-H柱进行HPLC分析,对映体过量为89%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=99∶1,流速=1mL/min,温度=28℃,tr(major)=8.3min,tr(minor)=9.7min。[α]D 26.6=-48.40(c=1.0,CHCl3)。
1H NMR(600MHz,CDCl3)δ7.80(d,J=7.2Hz,1H),7.76(d,J=7.5Hz,1H),7.74-7.68(m,3H),7.41(q,J=5.3Hz,3H),7.36(td,J=8.5,7.4,1.2Hz,1H),7.29-7.21(m,4H),7.10-7.07(m,1H),6.99-6.95(m,1H),6.72(d,J=7.7Hz,1H),6.35(d,J=7.9Hz,1H),1.92(d,J=16.0Hz,1H),1.81(d,J=16.0Hz,1H),1.42-1.34(m,2H),1.23(s,6H),1.20(s,6H),1.09(ddd,J=16.6,10.5,6.3Hz,1H),1.00(ddd,J=16.5,10.4,6.5Hz,1H)。13C NMR(151MHz,CDCl3)δ157.14,156.34,155.96,139.75,138.89,136.81,136.63,134.58,132.95,130.42,129.35,127.97,127.91,127.64,126.90,126.64,126.54,125.80,124.24,124.13,119.57,83.12,62.24,24.86,24.74,22.71,8.14。HRMS(EI,m/z)精确质量计算C34H35[11B]O2Si[M+]:514.2494,实测值:514.2514。
实施例35
根据方法F,用相应的二氢硅烷(32.6mg,0.1mmol),甲基-2,3-O-异亚丙基-D-呋喃呋喃糖苷乙烯基醚(51mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=10/1),得到产物3af,为无色油状物(36.2mg,0.065mmol,收率:65%)。使用ChiralpakAD-H柱进行HPLC分析,非对映体过量为93%de。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=98∶2,流速=1.0mL/min,温度=28℃,tr(minor)=8.6min,tr(major)=9.0min。[α]D 26.7=-65.30(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.58(d,J=7.1Hz,1H),7.50-7.43(m,2H),7.40(ddd,J=8.2,6.9,1.4Hz,1H),7.35(d,J=7.5Hz,1H),7.27-7.21(m,1H),6.88(d,J=8.6Hz,2H),4.94(s,1H),4.60(d,J=6.0Hz,1H),4.53(d,J=5.9Hz,1H),4.28(dd,J=8.4,6.3Hz,1H),3.92-3.78(m,4H),3.61(ddd,J=9.1,6.8,2.1Hz,2H),3.40(dd,J=9.6,6.1Hz,1H),3.33(d,J=8.6Hz,1H),3.28(s,3H),3.23-3.09(m,4H),1.54-1.45(m,5H),1.42(s,3H),1.31(s,3H),1.25(d,J=15.6Hz,4H),1.18(d,J=15.2Hz,1H)。13C NMR(151MHz,CDCl3)δ162.42,151.81,135.60,135.49,132.96,130.04,125.86,125.64,123.67,114.68,112.23,109.19,85.11,85.01,82.17,71.14,68.27,66.80,54.72,48.47,43.67,34.09,33.66,27.82,26.42,24.96,16.49。HRMS(ESI,m/z)精确质量计算C31H44NO6Si[(M+H)+]:554.2932,实测值:554.2918。
实施例36
根据方法F,用相应的二氢硅烷(27.0mg,0.1mmol),2,3,4,5-二-O-异亚丙基-β-D-果糖基葡萄糖乙烯基醚(63mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=10/1),得到产物3ag,为无色油状物(30.1mg,0.054mmol,收率:54%)。使用Chiralpak OD-3色谱柱进行HPLC分析,非对映过量为95%de。HPLC条件波长=220nm,洗脱液:正己烷/异丙醇=99.5∶0.5,流速=1.0mL/min,温度=28℃,tr(major)=12.8min,tr(minor)=14.1min。[α]D 27.5=-63.30(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.64-7.45(m,2H),7.40-7.28(m,3H),7.24(s,1H),7.05(d,J=2.6Hz,1H),6.95(dd,J=8.5,2.7Hz,1H),4.57(dd,J=7.9,2.6Hz,1H),4.35(d,J=2.6Hz,1H),4.24-4.15(m,1H),3.87(dd,J=13.0,1.8Hz,1H),3.80(s,3H),3.75-3.66(m,2H),3.66-3.57(m,1H),3.54-3.43(m,2H),1.56-1.47(m,5H),1.43(s,3H),1.38(s,3H),1.35(s,3H),1.32(s,3H),1.26-1.19(m,5H)。13C NMR(101MHz,CDCl3)δ157.89,154.76,136.41,134.25,129.32,127.92,124.73,116.97,116.37,108.87,108.41,102.69,71.74,71.03,70.20,70.02,68.89,60.99,55.34,43.01,34.24,33.92,27.73,26.51,25.86,25.32,24.03,16.23。HRMS(ESI,m/z)精确质量计算C31H42O7NaSi[(M+Na)+]:577.2592,实测值:577.2581。
实施例37
根据方法F,用相应的二氢硅烷(24.0mg,0.1mmol),(-)-薄荷基乙烯基醚(40mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3ah,为无色油状物(37.8mg,0.090mmol,收率:90%)。使用ChiralpakIB柱进行HPLC分析,非对映过量为89%de。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=0.5mL/min,温度=28℃,tr(minor)=9.9min,tr(major)=10.1min。[α]D 27.3=-71.40(c=1.0,CHCl3)。
1H NMR(600MHz,CDCl3)δ7.62(d,J=7.2Hz,1H),7.57(dd,J=7.6,1.7Hz,2H),7.42(td,J=7.5,1.4Hz,1H),7.40-7.31(m,4H),7.28-7.25(m,1H),3.81-3.71(m,1H),3.69(dq,J=9.2,7.0Hz,0H),3.51-3.41(m,1H),3.36(dt,J=9.2,7.0Hz,0H),3.04(td,J=10.6,4.1Hz,0H),2.98(td,J=10.5,4.2Hz,1H),2.13(pd,J=7.0,2.6Hz,1H),2.00(dtd,J=12.2,3.7,1.9Hz,1H),1.61(dddd,J=22.6,9.9,6.2,3.1Hz,3H),1.53(dd,J=8.8,7.4Hz,2H),1.45(s,3H),1.30-1.27(m,4H),1.23(d,J=15.3Hz,1H),1.18(ddd,J=13.2,8.1,2.5Hz,1H),0.96-0.92(m,1H),0.89(d,J=6.5Hz,3H),0.86(d,J=7.1Hz,3H),0.85-0.77(m,2H),0.70(d,J=6.9Hz,3H)。13C NMR(151MHz,CDCl3)δ162.51,136.84,135.45,134.33,133.03,130.12,129.16,127.80,125.89,123.70,78.79,64.96,48.26,43.73,40.62,34.57,34.06,33.67,31.52,27.64,25.44,23.33,22.31,21.00,16.87,16.20。HRMS(EI,m/z)精确质量计算C28H40OSi[M+]:420.2843,实测值:420.2841。
实施例38
根据方法F,用相应的二氢硅烷(36.3mg,0.1mmol),二氢胆固醇乙烯基醚(91.2mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3ai,为白色固体(63.6mg,0.082mmol,收率:82%)。使用ChiralpakOD-3色谱柱进行HPLC分析,非对映过量为91%de。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=98.5∶1.5,流速=0.5mL/min,温度=28℃,tr(minor)=7.2min,tr(major)=7.6min。[α]D 27.6=-30.70(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.81(d,J=7.3Hz,1H),7.77-7.66(m,4H),7.50-7.37(m,3H),7.37-7.30(m,1H),7.29-7.19(m,3H),7.17(d,J=7.5Hz,1H),7.11-7.06(m,1H),6.96(td,J=7.5,1.1Hz,1H),6.70(d,J=7.6Hz,1H),6.34(d,J=7.9Hz,1H),3.72(td,J=8.2,3.2Hz,2H),3.17(tt,J=10.8,4.5Hz,1H),1.98-1.82(m,3H),1.78(td,J=9.8,8.8,4.9Hz,2H),1.72-1.60(m,4H),1.58-1.43(m,4H),1.36-1.18(m,11H),1.05(dddt,J=39.4,15.6,10.5,6.4Hz,9H),0.91-0.84(m,10H),0.77(s,3H),0.69-0.51(m,4H)。13C NMR(101MHz,CDCl3)δ156.96,156.25,155.82,139.76,138.98,136.75,136.46,134.55,132.97,130.52,129.45,128.00,127.90,127.68,126.96,126.71,126.64,125.85,124.26,123.94,119.68,119.61,78.40,64.10,62.34,56.51,56.30,54.42,44.84,42.60,40.06,39.51,36.99,36.17,35.78,35.49,34.84,32.13,28.86,28.30,28.24,28.00,24.21,23.83,23.80,22.81,22.56,21.21,18.67,17.66,12.29,12.06。HRMS(DART,m/z)精确质量计算C55H74ONSi[(M+NH4)+]:792.5534,实测值:792.5527。
实施例39
根据方法F,用相应的二氢硅烷(32.6mg,0.1mmol),β-雌二醇乙烯基醚(68.7mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=8/1),得到为白色固体的产物3aj(49.5mg,0.078mmol,收率:78%)。使用ChiralpakAD-H柱进行HPLC分析,非对映体过量为91%de。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=98∶2,流速=1.0mL/min,温度=28℃,tr(minor)=6.1min,tr(major)=6.9min。[α]D 26.8=-5.80(c=1.0,CHCl3)。
1H NMR(600MHz,CDCl3)δ7.57(d,J=7.2Hz,1H),7.47(d,J=8.5Hz,2H),7.40-7.36(m,1H),7.34(d,J=7.7Hz,1H),7.24-7.20(m,1H),7.19(d,J=8.6Hz,1H),6.87(d,J=8.1Hz,2H),6.70(dd,J=8.6,2.8Hz,1H),6.62(d,J=2.6Hz,1H),3.84(t,J=4.8Hz,4H),3.76(s,3H),3.62(t,J=7.8Hz,2H),3.32(t,J=8.4Hz,1H),3.17(t,J=4.9Hz,4H),2.89-2.78(m,2H),2.24(dq,J=13.0,3.7Hz,1H),2.15(td,J=11.3,4.1Hz,1H),1.94(ddt,J=23.8,12.6,3.8Hz,2H),1.85(ddd,J=12.6,5.8,2.8Hz,1H),1.64(dddd,J=12.5,9.8,6.9,3.3Hz,2H),1.46(dt,J=11.9,3.7Hz,4H),1.41(s,4H),1.33-1.24(m,6H),1.21(d,J=15.1Hz,1H),1.17-1.11(m,1H),0.74(s,3H)。13C NMR(151MHz,CDCl3)δ162.39,157.37,151.74,137.96,136.26,136.12,135.62,132.92,132.73,129.91,126.28,125.77,123.61,114.67,113.75,111.41,88.77,66.82,66.58,55.16,50.20,48.59,43.91,43.65,43.22,38.61,37.95,34.11,33.68,29.81,28.05,27.97,27.21,26.46,23.08,16.89,11.73。HRMS(ESI,m/z)精确质量计算C41H54NO3Si[(M+H)+]:636.3868,实测值:636.3856。
实施例40
根据方法F,用相应的二氢硅烷(32.6mg,0.1mmol),2-环丙基-4-(4-氟苯基)-3-((乙烯基氧基)甲基)喹啉(70.3mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE(1.0mL)中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=6/1),得到产物3ak,为无色油状物(34.2mg,0.053mmol,收率:53%)。使用ChiralpakAD-H柱进行HPLC分析,对映体过量为93%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=98∶2,流速=1.0mL/min,温度=28℃,tr(minor)=6.4min,tr(major)=7.4min。[α]D 26.7=-19.60(c=1.0,CHCl3)。
1H NMR(600MHz,CDCl3)δ8.00(d,J=8.5Hz,1H),7.62(ddd,J=8.4,5.4,2.9Hz,1H),7.49(dd,J=7.2,1.3Hz,1H),7.42-7.37(m,3H),7.36(d,J=7.8Hz,1H),7.33-7.29(m,2H),7.22-7.11(m,5H),6.81(d,J=8.5Hz,2H),4.48(d,J=10.6Hz,1H),4.42(d,J=10.6Hz,1H),3.87-3.82(m,4H),3.58-3.45(m,2H),3.19-3.07(m,4H),2.55(tt,J=8.1,4.8Hz,1H),1.52-1.43(m,2H),1.39(s,3H),1.37-1.31(m,2H),1.27(s,3H),1.23(d,J=15.1Hz,1H),1.15(d,J=15.1Hz,1H),1.05(dd,J=8.2,3.3Hz,2H)。13C NMR(151MHz,CDCl3)δ162.80,162.41(d,J=247.3Hz),162.38,151.81,135.62,135.48,132.91,132.45(d,J=3.3Hz),131.56,131.50,131.46(d,J=7.9Hz),130.04,128.92,128.85,127.32,126.33,126.01,125.82,125.45,125.20,123.65,115.11(d,J=22.2Hz),114.58,67.51,66.78,48.39,43.63,34.07,33.61,27.84,16.62,14.49,9.95,9.73。19F NMR(565MHz,CDCl3)δ-113.93。HRMS(ESI,m/z)精确质量计算C41H44N2O2FSi[(M+H)+]:643.3151,实测值:643.3148。
实施例41
根据方法F,用相应的二氢硅烷(24.0mg,0.1mmol),(1R,1′R,4R,4′R)-4-(3,4-二氟苯基)-4′-乙烯基-1,1′-联(环己烷)(67.0mg,0.22mmol),[Rh(cod)Cl]2(1mg,0.002mmol)和(R,Sp)-Josiphos(2.2mg,0.004mmol)在无水DCE中、100℃反应1h。然后将反应混合物浓缩并通过制备TCL纯化(石油醚/乙酸乙酯=100/1),得到产物3a1,为无色油状物(44.7mg,0.082mmol,收率:82%)。使用Chiralpak OD-3柱进行HPLC分析,对映体过量为91%ee。HPLC条件:波长=220nm,洗脱液:正己烷/异丙醇=100∶0,流速=1.0mL/min,温度=28℃,tr(major)=20.6min,tr(minor)=28.9min。[α]D 26.7=-37.00(c=1.0,CHCl3)。
1H NMR(400MHz,CDCl3)δ7.61(dt,J=7.3,1.0Hz,1H),7.59-7.47(m,2H),7.43(ddd,J=8.2,6.9,1.4Hz,1H),7.40-7.30(m,4H),7.30-7.23(m,1H),7.12-6.95(m,2H),6.90(ddd,J=8.6,4.2,1.8Hz,1H),2.42(tt,J=12.1,3.1Hz,1H),1.83(ddd,J=40.8,25.3,12.0Hz,8H),1.45(s,3H),1.41-1.24(m,8H),1.21(d,J=15.1Hz,1H),1.18-0.91(m,9H),0.85(q,J=12.1Hz,2H)。13C NMR(151MHz,CDCl3)δ162.52,150.13(dd,J=246.7,12.7Hz),148.48(dd,J=245.3,13.1Hz),144.87(t,J=4.4Hz),137.51,135.98,134.33,132.92,129.99,129.04,127.80,125.81,123.70,122.47(dd,J=6.0,3.3Hz),116.72(d,J=16.4Hz),115.38(d,J=16.4Hz),43.84,43.68,43.32,42.74,40.83,34.55,34.08,33.76,33.01(d,J=3.8Hz),31.45,30.16,30.00,27.18,11.55。19F NMR(565MHz,CDCl3)δ-138.64(d,J=21.9Hz),-142.54(d,J=21.5Hz)。HRMS(DART,m/z)精确质量计算C36H48NF2Si[(M+NH4)+]:560.3519,实测值:560.3521。
以上所述,仅为本发明的具体实施方式,但本发明的保护范围并不局限于此,任何属于本技术领域的技术人员在本发明揭露的技术范围内,可轻易想到的变化或替换,都应涵盖在本发明的保护范围之内。因此,本发明的保护范围应该以权利要求的保护范围为准。
Claims (10)
4.根据权利要求1所述的化合物,其特征在于,所述取代苯基为卤素、三氟甲基、甲氧基或频哪醇硼取代的苯基。
8.根据权利要求6或7所述的制备方法,其特征在于,所述配体的用量至少是4mol%,所述铑催化剂的用量至少是2mol%。
9.根据权利要求6或7所述的制备方法,其特征在于,所述式II化合物和式III化合物的摩尔比为1∶(1~3)。
10.根据权利要求6或7所述的制备方法,其特征在于,所述反应以甲苯、二氯乙烷、正己烷、1,4-二氧六环中的至少一种为溶剂;所述反应的时间至少是1h。
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