CN114249635A - 一种新型手性(r)-联萘酚钛配合物及其制备方法和应用 - Google Patents
一种新型手性(r)-联萘酚钛配合物及其制备方法和应用 Download PDFInfo
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- CN114249635A CN114249635A CN202111386058.0A CN202111386058A CN114249635A CN 114249635 A CN114249635 A CN 114249635A CN 202111386058 A CN202111386058 A CN 202111386058A CN 114249635 A CN114249635 A CN 114249635A
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- chiral
- binaphthol
- solvent
- titanium complex
- titanium
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- 239000010936 titanium Substances 0.000 title claims abstract description 72
- 229910052719 titanium Inorganic materials 0.000 title claims abstract description 70
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 title claims abstract description 67
- PPTXVXKCQZKFBN-UHFFFAOYSA-N (S)-(-)-1,1'-Bi-2-naphthol Chemical compound C1=CC=C2C(C3=C4C=CC=CC4=CC=C3O)=C(O)C=CC2=C1 PPTXVXKCQZKFBN-UHFFFAOYSA-N 0.000 title claims abstract description 63
- 238000002360 preparation method Methods 0.000 title abstract description 28
- 238000010668 complexation reaction Methods 0.000 title description 2
- 239000002904 solvent Substances 0.000 claims abstract description 72
- 238000006243 chemical reaction Methods 0.000 claims abstract description 36
- SHALBPKEGDBVKK-VOTSOKGWSA-N danishefsky's diene Chemical compound CO\C=C\C(=C)O[Si](C)(C)C SHALBPKEGDBVKK-VOTSOKGWSA-N 0.000 claims abstract description 35
- 239000003054 catalyst Substances 0.000 claims abstract description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000003446 ligand Substances 0.000 claims abstract description 11
- 238000006077 hetero Diels-Alder cycloaddition reaction Methods 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims abstract description 7
- 125000002091 cationic group Chemical group 0.000 claims abstract description 4
- 150000001450 anions Chemical class 0.000 claims abstract description 3
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- 239000000203 mixture Substances 0.000 claims description 47
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 40
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 40
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- 239000007788 liquid Substances 0.000 claims description 20
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- 238000004064 recycling Methods 0.000 claims description 19
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 238000001035 drying Methods 0.000 claims description 11
- JGTNAGYHADQMCM-UHFFFAOYSA-N perfluorobutanesulfonic acid Chemical group OS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F JGTNAGYHADQMCM-UHFFFAOYSA-N 0.000 claims description 11
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 10
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- XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Inorganic materials O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 claims description 8
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- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 7
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- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 claims description 7
- WMPDAIZRQDCGFH-UHFFFAOYSA-N 3-methoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1 WMPDAIZRQDCGFH-UHFFFAOYSA-N 0.000 claims description 6
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 claims description 6
- NUJGJRNETVAIRJ-UHFFFAOYSA-N octanal Chemical compound CCCCCCCC=O NUJGJRNETVAIRJ-UHFFFAOYSA-N 0.000 claims description 6
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- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 3
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- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 3
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- 239000001431 2-methylbenzaldehyde Substances 0.000 claims description 3
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- SRWILAKSARHZPR-UHFFFAOYSA-N 3-chlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1 SRWILAKSARHZPR-UHFFFAOYSA-N 0.000 claims description 3
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 claims description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 claims description 3
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 claims description 3
- 238000005698 Diels-Alder reaction Methods 0.000 claims description 3
- 229940117916 cinnamic aldehyde Drugs 0.000 claims description 3
- KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000012043 crude product Substances 0.000 claims description 3
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- JQFKMPJULDLMOJ-UHFFFAOYSA-M silver;2,3,4,5,6-pentafluorobenzenesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C1=C(F)C(F)=C(F)C(F)=C1F JQFKMPJULDLMOJ-UHFFFAOYSA-M 0.000 claims description 3
- DVWQNBIUTWDZMW-UHFFFAOYSA-N 1-naphthalen-1-ylnaphthalen-2-ol Chemical compound C1=CC=C2C(C3=C4C=CC=CC4=CC=C3O)=CC=CC2=C1 DVWQNBIUTWDZMW-UHFFFAOYSA-N 0.000 claims description 2
- QVTPWONEVZJCCS-UHFFFAOYSA-N 2-formylbenzonitrile Chemical compound O=CC1=CC=CC=C1C#N QVTPWONEVZJCCS-UHFFFAOYSA-N 0.000 claims description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 2
- NWXNEKFPUYDMQQ-UHFFFAOYSA-N FC(C(C(C(C(F)(F)[Ag])(F)F)(F)F)(F)F)(C(C(C(F)(F)F)(F)F)(F)F)F Chemical group FC(C(C(C(C(F)(F)[Ag])(F)F)(F)F)(F)F)(C(C(C(F)(F)F)(F)F)(F)F)F NWXNEKFPUYDMQQ-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 150000001768 cations Chemical class 0.000 claims description 2
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 125000005504 styryl group Chemical group 0.000 claims description 2
- 239000000758 substrate Substances 0.000 claims description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
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- IKMBXKGUMLSBOT-UHFFFAOYSA-N 2,3,4,5,6-pentafluorobenzenesulfonic acid Chemical group OS(=O)(=O)C1=C(F)C(F)=C(F)C(F)=C1F IKMBXKGUMLSBOT-UHFFFAOYSA-N 0.000 description 8
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- ZWYDDDAMNQQZHD-UHFFFAOYSA-L titanium(ii) chloride Chemical compound [Cl-].[Cl-].[Ti+2] ZWYDDDAMNQQZHD-UHFFFAOYSA-L 0.000 description 7
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- VEUMANXWQDHAJV-UHFFFAOYSA-N 2-[2-[(2-hydroxyphenyl)methylideneamino]ethyliminomethyl]phenol Chemical compound OC1=CC=CC=C1C=NCCN=CC1=CC=CC=C1O VEUMANXWQDHAJV-UHFFFAOYSA-N 0.000 description 2
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- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
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- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 2
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- WGYGSZOQGYRGIP-MWDXBVQZSA-N (3r,4s,5s)-3-hydroxy-5-[(r)-hydroxy(phenyl)methyl]-1-methyl-4-phenylpyrrolidin-2-one Chemical compound C1([C@@H](O)[C@H]2N(C([C@H](O)[C@H]2C=2C=CC=CC=2)=O)C)=CC=CC=C1 WGYGSZOQGYRGIP-MWDXBVQZSA-N 0.000 description 1
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Images
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
- C07C39/235—Metal derivatives of a hydroxy group bound to a six-membered aromatic ring
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
- B01J31/2208—Oxygen, e.g. acetylacetonates
- B01J31/2226—Anionic ligands, i.e. the overall ligand carries at least one formal negative charge
- B01J31/223—At least two oxygen atoms present in one at least bidentate or bridging ligand
- B01J31/2239—Bridging ligands, e.g. OAc in Cr2(OAc)4, Pt4(OAc)8 or dicarboxylate ligands
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/64—Preparation of O-metal compounds with O-metal group bound to a carbon atom belonging to a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/32—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
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Abstract
本发明属于催化有机合成领域，具体公开了一种新型手性(R)‑联萘酚钛配合物及其制备方法和应用。所述的配合物是阳离子型配合物，其中钛原子跟手性(R)‑联萘酚配体以及水分子配位形成阳离子部分，对应阴离子与钛阳离子部分形成离子键。手性(R)‑联萘酚钛配合物具有高的空气稳定性和强的路易斯酸性，能够高效催化Danishefsky二烯与醛的Hetero‑Diels‑Alder反应，合成手性(R)‑吡喃衍生物；本方法克服传统手性路易斯酸催化剂易潮解，催化活性低，反应条件苛刻，无法循环利用等不足，提供了一种制备手性(R)‑吡喃衍生物，具有操作简便，产物产率高，立体选择性高，溶剂无需除水，催化剂可重复利用等优点。
Description
技术领域
本发明属于催化有机合成领域，具体涉及一种新型手性(R)-联萘酚钛配合物及其制备方法和应用。
背景技术
手性有机金属路易斯酸在不对称有机合成，医药和化工等领域具有广泛的应用。如在医药领域，合成手性药物的基本骨架结构，如：黄皮酰胺、地尔卓硫、福司曲星、生物碱Isoborreverine V-1等均涉及了手性有机金属路易斯酸催化剂。目前，尽管许多手性有机金属配合物能够高效的催化合成立体选择性高的有机活性小分子，然而，使用手性过渡金属配合物作为催化剂，尤其是贵金属配合物作为催化剂，如：钯，铂，铱，铑等配合物，由于其成本高，在我们国家的储量极低，限制了其深入应用。
相比于贵金属催化剂，过渡金属钛也常用于制备手性金属路易斯酸催化剂。目前，关于手性钛化合物催化不对称反应多数集中以下两方面：(1)单组分催化体系：使用单一手性钛配合物作为催化剂，手性配体如：Binol、Salen、Taddol配体等。(2)双(多)组分催化体系：钛盐(TiCl4、Ti(Oi-Pr)4、TiCl2(Oi-Pr)2等)+手性配体(Binol、Salen、Taddol配体等)+其它，(锂试剂，银盐，分子筛等)。近年来，国际上在手性有机钛路易斯酸催化不对称反应具有重要贡献的课题组有：Keiji Maruoka等使用手性氧桥双核Binol异丙氧基钛配合物催化硝酮和丙烯醛发生环加成反应，再经过NaBH4水解，得到高立体选择性产物异恶唑烷。JamesD.White等使用(S)-BINOL-TiCl2配合物催化苯醌和二烯烃通过Diels-Alder反应得到环加成产物，经进一步转变可得到吲哚生物碱伊菠胺(Ibogamine)。ShūKobayashia等通过使用Ti(Oi-Pr)4/手性三齿BINOL衍生物催化体系催化氮杂环丙烷与苯胺的开环反应，高立体选择性的得到对应的产物。但是以上这些手性钛配合物大多数易潮解，反应需要在严格无水无氧条件下进行，且部分反应的产率和产物立体选择性一般，可能是由于多组分体系会造成副产物产生以及条件苛刻使反应难以控制。此外，这些钛配合物均不能重复利用。
手性(R)-吡喃酮是合成许多天然产物和药物分子的重要中间体，如，天然产物Mevinlin内酯，HemibrevetoxinB 9等。目前主要通过Ti(Oi-Pr)4+手性(R)-联萘酚配体催化Hetero-Diels-Alder反应合成(J.Org.Chem.2002,67,2175-2182)。但是，该方法需要无水氮气保护条件，催化剂用量大，不能回收利用等不足。前期工作，长链的全氟烷基磺酸基团能够增强配合物稳定性和路易斯酸性。另外，长链全氟烷基磺酸金属配合物在非极性溶剂以及二氯甲烷中溶解性几乎为零。当反应完毕后，加入二氯甲烷溶剂，能够将催化剂自动分离，达到重复利用(Dalton Transactions,2014,43:11696-11708)。基于此理念，我们拟采用具有手性配体的(R)-联萘酚与中心金属钛形成Ti-O(N)键构建稳定的手性(R)-联萘酚钛路易斯酸主结构，再引入全氟烷(苯)基磺酸功能基团，合成对空气稳定的手性(R)-联萘酚钛配合物，并将其应用于催化Danishefsky二烯与醛的Hetero-Diels-Alder反应，合成手性(R)-吡喃酮化合物。目前，国内外还没有关于手性(R)-联萘酚全氟烷基钛配合物的制备方法以及催化不对称Hetero-Diels-Alder反应的公开文献和专利申请。
发明内容
针对上述问题本发明提供了一种新型手性(R)-联萘酚钛配合物及其制备方法和应用。用于催化Danishefsky二烯与醛的Hetero-Diels-Alder反应，合成手性(R)-吡喃酮化合物；该催化剂具有空气稳定性高、酸性强、热稳定性高，催化活性强及立体选择性高等优点。
为了达到上述目的，本发明采用了下列技术方案：
本发明提供一种新型手性(R)-联萘酚钛配合物，其结构式(I)为：
其中，阳离子由钛原子与手性(R)-联萘酚配体和两个水分子配位形成，另外两个阴离子X-与配合物的阳离子部分形成离子键。
进一步，所述手性(R)-联萘酚配体为(R)-BINOL(BINOL：联萘酚)和(R)-H8-BINOL中的任意一种；所述X为全氟辛基磺酸基团OSO2C8F17、五氟苯基磺酸基团OSO2C6F5、全氟己基磺酸基团OSO2C6F13或全氟丁基磺酸基团OSO2C4F9中的任意一种。
本发明还提供一种上述新型手性(R)-联萘酚钛配合物的制备方法，包括以下步骤：将手性(R)-联萘酚钛配合物二氯化物溶解于溶剂中，并在N2保护下，将银盐加入，室温下避光反应2-4h，过滤，滤液加入正己烷，直至分层，-20℃冷冻24h，析出配合物为催化剂手性(R)-联萘酚钛配合物。手性(R)-联萘酚钛二氯化物合成方法见文献TetrahedronLetters,1991,32,935-938.
进一步，所述溶剂为四氢呋喃、丙酮、乙腈、乙醇中的任意一种；所述银盐为全氟辛基磺酸银AgOSO2C8F17、五氟苯基磺酸银AgOSO2C6F5、全氟己基磺酸银AgOSO2C6F13或全氟丁基磺酸银AgOSO2C4F9中的任意一种；所述手性(R)-联萘酚钛配合物二氯化物与银盐的物质的量摩尔数比为1:2，每1.0mmol手性(R)-联萘酚钛配合物二氯化物用溶剂10mL。
本发明还提供一种上述新型手性(R)-联萘酚钛配合物的应用，用作催化剂，催化Danishefsky二烯(反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯)与醛的Hetero-Diels-Alder反应，合成手性(R)-吡喃酮化合物。
进一步，所述手性(R)-联萘酚钛配合物催化反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯与醛的Hetero-Diels-Alder反应，合成手性(R)-吡喃酮化合物的具体过程为：将醛，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯和溶剂加入反应容器中，加入手性(R)-联萘酚钛配合物作催化剂，在0-25℃下反应2-24h，反应完毕后，旋干溶剂，加入二氯甲烷萃取，过滤回收手性(R)-联萘酚钛配合物催化剂用于重复利用，滤液滴入三氟乙酸，搅拌30分钟，再加入饱和碳酸氢钠，分液，水洗，再用二氯甲烷萃取，合并萃取液，无水硫酸钠干燥，萃取液经溶剂蒸发后，得到黄色油状混合物，粗产品经柱层析分离得到手性(R)-吡喃酮化合物(II)。
进一步，所述手性(R)-吡喃酮化合物的结构式(II)为：
其中，R1为苯基、间甲基苯基、间甲氧基苯基、对甲氧基苯基、对氯苯基、对氟苯基、间氯苯基、对溴苯基、对硝基苯基、对氰基苯基、1-萘基、苯乙烯基、2-糠基、2-吡啶基、正庚基中的任意一种。
进一步，所述醛为苯甲醛、3-甲基苯甲醛、3-甲氧基苯甲醛、4-甲氧基苯甲醛、4-氯苯甲醛、4-氟苯甲醛、4-溴苯甲醛、糠醛、肉桂醛、3-氯苯甲醛、氰基苯甲醛、2-吡啶甲醛、1-萘甲醛、对硝基苯甲醛、正辛醛中的任意一种；所述溶剂为四氢呋喃、乙腈、二氯乙烷、乙醚、甲苯中的任意一种。
进一步，所述醛，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯和手性(R)-联萘酚钛配合物的物质的量摩尔数比为1:1.2:0.05；每1mmol醛用溶剂2mL，三氟乙酸5滴，饱和碳酸氢钠2mL，二氯甲烷20mL；所述催化剂的用量为1.0-10mol％，催化剂用量以反应底物醛的摩尔数为基准；催化剂可重复利用5次以上。
与现有技术相比本发明具有以下优点：
本发明制备了一种新型手性(R)-联萘酚钛配合物，该配合物可用于催化反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯与醛的Hetero-Diels-Alder反应，合成手性(R)-吡喃酮化合物，为制备手性(R)-吡喃酮化合物开辟了一条新的有效简便途径。
本发明新型手性(R)-联萘酚钛配合物的催化剂稳定性高且催化活性高，目标产物产率较高，立体选择性高，催化剂能够重复利用5次以上，实验操作简便，溶剂无需除水。
附图说明
图1为本发明所提供的制备新型手性(R)-联萘酚钛配合物的路线图以及催化Danishefsky二烯与醛的Hetero-Diels-Alder反应，合成手性(R)-吡喃酮衍生物的路线图。
具体实施方式
本发明所提供的一种手性(R)-联萘酚钛配合物的合成路线，请参见附图1：将手性(R)-联萘酚钛配合物二氯化物溶解于四氢呋喃、丙酮、乙腈、乙醇溶剂中的一种，N2保护下，向其中加入银盐中的一种，室温下避光反应2-4h，过滤，滤液加入正己烷，直至分层，-20℃冷冻24h，析出配合物，抽滤得黄色固体手性(R)-联萘酚钛配合物。
注：所述银盐为：全氟辛基磺酸银AgOSO2C8F17、五氟苯基磺酸银AgOSO2C6F5、全氟己基磺酸银AgOSO2C6F13或全氟丁基磺酸银AgOSO2C4F9中的一种。手性(R)-联萘酚钛二氯化物合成方法见文献Tetrahedron Letters,1991,32,935-938.
将手性(R)-联萘酚钛配合物作为催化剂应用于催化Danishefsky二烯与醛的Hetero-Diels-Alder反应，合成手性(R)-吡喃酮化合物。制备手性(R)-吡喃酮化合物可依据：将醛，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯和溶剂加入反应容器中，在0-25℃下反应2-24h。反应完毕后，旋干溶剂，加入二氯甲烷，过滤回收催化剂用于重复利用。滤液滴入5滴三氟乙酸，搅拌30分钟。再加入2mL饱和碳酸氢钠。分液，水洗。再用20毫升二氯甲烷萃取，合并萃取液。无水硫酸钠干燥，萃取液经溶剂蒸发后，得到黄色油状混合物。粗产品经柱层析分离得目标化合物。
注：上述反应所述溶剂均为四氢呋喃、乙腈，二氯乙烷、乙醚、甲苯中的一种；所述催化剂的用量为1.0-10mol％；催化剂可重复利用5次以上。
下面结合具体的制备例对本发明做进一步说明：
一、新型手性(R)-联萘酚钛配合物催化剂的合成
制备例1
将手性(R)-BINOL二氯化物(1.0mmol)溶于10mL四氢呋喃(THF)中，N2保护下，加入全氟辛基磺酸银(2.0mmol)，室温下避光反应2h，过滤，滤液加入正己烷，直至分层。-20℃冷冻24h，析出黄色固体，产率78％。
制备例2
将手性(R)-BINOL钛二氯化物(1.0mmol)溶于10mL乙腈(CH3CN)中，N2保护下，加入全氟苯基磺酸银(2.0mmol)，室温下避光反应3h，过滤，滤液加入正己烷，直至分层。-20℃冷冻24h，析出黄色色固体，产率81％。
制备例3
将手性(R)-H8-BINOL二氯化物(1.0mmol)溶于10mL乙醇中，N2保护下，加入全氟己基磺酸银(2.0mmol)，室温下避光反应3h，过滤，滤液加入正己烷，直至分层。-20℃冷冻24h，析出黄色固体，产率77％。
制备例4
将手性(R)-H8-BINOL钛二氯化物(1.0mmol)溶于10mL丙酮中，N2保护下，加入全氟丁基磺酸银(2.0mmol)，室温下避光反应4h，过滤，滤液加入正己烷，直至分层。-20℃冷冻24h，析出黄色固体，产率74％。
二、手性(R)-联萘酚钛配合物催化合成手性(R)-吡喃酮化合物
制备例1
在50mL圆底烧瓶中加入苯甲醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，溶剂THF(2mL)和手性(R)-BINOL钛全氟辛基磺酸配合物(X＝OSO2C8F17)(0.05mmol)，0℃下搅拌12h。反应结束后旋干溶剂，剩余物中用CH2Cl2萃取3次，收集固体催化剂以回收利。滤液滴入5滴三氟乙酸，搅拌30分钟。再加入2mL饱和碳酸氢钠。分液，水洗。再用20mL二氯甲烷萃取，合并萃取液。无水硫酸钠干燥，萃取液经溶剂蒸发后，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-苯基-2H-吡喃-4(3H)-酮，产率92％。光学产率：95％ee:determined by HPLC on Chiralcel OD column hexane:isopropanol＝90:10,flow rate＝1.0mL/min,tR1＝11.1min(minor),tR2＝13.0min(major).
制备例2
在50mL圆底烧瓶中加入3-甲基苯甲醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，溶剂乙腈(2mL)和手性(R)-BINOL钛全丁基磺酸配合物(X＝OSO2C4F9)(0.05mmol)，5℃下搅拌4h。反应结束后旋干溶剂，剩余物中用CH2Cl2萃取3次，收集固体催化剂以回收利。滤液滴入5滴三氟乙酸，搅拌30分钟。再加入2mL饱和碳酸氢钠。分液，水洗。再用20mL二氯甲烷萃取，合并萃取液。无水硫酸钠干燥，萃取液经溶剂蒸发后，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-(间甲苯基)-2H-吡喃-4(3H)-酮。产率88％，光学产率：92％ee:determined by HPLC on Chiralcel OD column,hexane:isopropanol＝90:10,flow rate＝1.0mL/min,tR1＝9.9min(minor),tR2＝11.7min(major).
制备例3
在50mL圆底烧瓶中加入3-甲氧基苯甲醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，溶剂乙醚(2mL)和手性(R)-H8-BINOL钛全氟苯基磺酸配合物(X＝OSO2C6F5)(0.05mmol)，25℃下搅拌12h。反应结束后旋干溶剂，剩余物中用CH2Cl2萃取3次，收集固体催化剂以回收利。滤液滴入5滴三氟乙酸，搅拌30分钟。再加入2mL饱和碳酸氢钠。分液，水洗。再用20mL二氯甲烷萃取，合并萃取液。无水硫酸钠干燥，萃取液经溶剂蒸发后，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-(间甲氧基苯基)-2H-吡喃-4(3H)-酮。产率94％，光学产率：86％ee:determined by HPLC on Chiralpak ADcolumn,hexane:isopropanol＝99.5:0.5,flow rate＝1.0mL/min,tR1＝29.8min(major),tR2＝33.7min(minor).
制备例4
在50mL圆底烧瓶中加入4-甲氧基苯甲醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，溶剂四氢呋喃(2mL)和手性(R)-H8-BINOL钛全氟辛基磺酸配合物(X＝OSO2C8F17)(0.01mmol)，0℃下搅拌24h。反应结束后旋干溶剂，剩余物中用CH2Cl2萃取3次，收集固体催化剂以回收利。滤液滴入5滴三氟乙酸，搅拌30分钟。再加入2mL饱和碳酸氢钠。分液，水洗。再用20mL二氯甲烷萃取，合并萃取液。无水硫酸钠干燥，萃取液经溶剂蒸发后，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-(对甲氧基苯基)-2H-吡喃-4(3H)-酮。产率96％，光学产率：94％ee:determined by HPLC on Chiralcel ODcolumn,hexane:isopropanol＝90:10,flow rate＝1.0mL/min,tR1＝15.5min(minor),tR2＝17.1min(major).
制备例5
在50mL圆底烧瓶中加入4-氯苯甲醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，溶剂甲苯(2mL)和手性(R)-H8-BINOL钛全氟丁基磺酸配合物(X＝OSO2C4F9)(0.10mmol)，25℃下搅拌2h。反应结束后旋干溶剂，剩余物中用CH2Cl2萃取3次，收集固体催化剂以回收利。滤液滴入5滴三氟乙酸，搅拌30分钟。再加入2mL饱和碳酸氢钠。分液，水洗。再用20mL二氯甲烷萃取，合并萃取液。无水硫酸钠干燥，萃取液经溶剂蒸发后，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-(对氯苯基)-2H-吡喃-4(3H)-酮。产率90％，光学产率：88％ee:determined by HPLC on Chiralcel OD column,hexane:isopropanol＝90:10,flow rate＝1.0mL/min,tR1＝15.5min(minor),tR2＝17.1min(major).
制备例6
在50mL圆底烧瓶中加入4-氟苯甲醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，溶剂二氯甲烷(2mL)和手性(R)-BINOL钛全氟丁基磺酸配合物(X＝OSO2C4F9)(0.05mmol)，10℃下搅拌16h。反应结束后旋干溶剂，剩余物中用CH2Cl2萃取3次，收集固体催化剂以回收利。滤液滴入5滴三氟乙酸，搅拌30分钟。再加入2mL饱和碳酸氢钠。分液，水洗。再用20mL二氯甲烷萃取，合并萃取液。无水硫酸钠干燥，萃取液经溶剂蒸发后，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-(对氟苯基)-2H-吡喃-4(3H)-酮。产率91％，光学产率：94％ee:determined by HPLC on Chiralcel OD column,hexane:isopropanol 90:10,flow rate＝1.0mL/min,tR1＝13.3min(minor),tR2＝17.0min(major).
制备例7
在50mL圆底烧瓶中加入4-溴苯甲醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，溶剂四氢呋喃(2mL)和手性(R)-BINOL钛全氟苯基磺酸配合物(X＝OSO2C6F5)(0.05mmol)，0℃下搅拌24h。反应结束后旋干溶剂，剩余物中用CH2Cl2萃取3次，收集固体催化剂以回收利。滤液滴入5滴三氟乙酸，搅拌30分钟。再加入2mL饱和碳酸氢钠。分液，水洗。再用20mL二氯甲烷萃取，合并萃取液。无水硫酸钠干燥，萃取液经溶剂蒸发后，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-(对溴苯基)-2H-吡喃-4(3H)-酮。产率89％，光学产率：93％ee:determined by HPLC on Chiralcel OD column,hexane:isopropanol 20:3,flow rate＝1.0mL/min,tR1＝8.4min(minor),tR2＝9.5min(major).
制备例8
在50mL圆底烧瓶中加入糠醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，溶剂四氢呋喃(2mL)和手性(R)-BINOL钛全氟苯基磺酸配合物(X＝OSO2C6F5)(0.05mmol)，0℃下搅拌24h。反应结束后旋干溶剂，剩余物中用CH2Cl2萃取3次，收集固体催化剂以回收利。滤液滴入5滴三氟乙酸，搅拌30分钟。再加入2mL饱和碳酸氢钠。分液，水洗。再用20mL二氯甲烷萃取，合并萃取液。无水硫酸钠干燥，萃取液经溶剂蒸发后，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-(呋喃-2-基)-2H-吡喃-4(3H)-酮。产率95％，光学产率：93％ee:determined by HPLC on Chiralcel OD column,hexane:isopropanol＝95:5,flow rate＝0.5mL/min,tR1＝31.0min(major),tR2＝33.6min(minor).
制备例9
在50mL圆底烧瓶中加入肉桂醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，溶剂乙腈(2mL)和手性(R)-H8-BINOL钛全氟苯基磺酸配合物(X＝OSO2C6F5)(0.05mmol)，0℃下搅拌18h。反应结束后旋干溶剂，剩余物中用CH2Cl2萃取3次，收集固体催化剂以回收利。滤液滴入5滴三氟乙酸，搅拌30分钟。再加入2mL饱和碳酸氢钠。分液，水洗。再用20mL二氯甲烷萃取，合并萃取液。无水硫酸钠干燥，萃取液经溶剂蒸发后，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-(反苯乙烯基)-2H-吡喃-4(3H)-酮。产率90％，光学产率：94％ee:determined by HPLC on Chiralcel OD column,hexane:isopropanol＝90:10,flow rate＝1mL/min,tR1＝19.0min(minor),tR2＝39.0min(major).
制备例10
在50mL圆底烧瓶中加入3-氯苯甲醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，溶剂二氯甲烷(2mL)和手性(R)-H8-BINOL钛全氟苯基磺酸配合物(X＝OSO2C6F5)(0.05mmol)，0℃下搅拌24h。反应结束后旋干溶剂，剩余物中用CH2Cl2萃取3次，收集固体催化剂以回收利。滤液滴入5滴三氟乙酸，搅拌30分钟。再加入2mL饱和碳酸氢钠。分液，水洗。再用20mL二氯甲烷萃取，合并萃取液。无水硫酸钠干燥，萃取液经溶剂蒸发后，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-(3-氯苯基)-2H-吡喃-4(3H)-酮。产率89％，光学产率：92％ee:determined by HPLC on Chiralcel OD column,hexane:isopropanol＝5:1,flow rate＝1mL/min,tR1＝8.14min(minor),tR2＝10.27min(major).
制备例11
在50mL圆底烧瓶中加入对氰基苯甲醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，溶剂四氢呋喃(2mL)和手性(R)-H8-BINOL钛全氟辛基磺酸配合物(X＝OSO2C8F17)(0.10mmol)，0℃下搅拌24h。反应结束后旋干溶剂，剩余物中用CH2Cl2萃取3次，收集固体催化剂以回收利。滤液滴入5滴三氟乙酸，搅拌30分钟。再加入2mL饱和碳酸氢钠。分液，水洗。再用20mL二氯甲烷萃取，合并萃取液。无水硫酸钠干燥，萃取液经溶剂蒸发后，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-(4-氰基苯基)-2H-吡喃-4(3H)-酮。产率92％，光学产率：97％ee:determined by HPLC on Chiralcel OD column,hexane:isopropanol＝5:1,flow rate＝1mL/min,tR1＝16.25min(minor),tR2＝19.60min(major).
制备例12
在50mL圆底烧瓶中加入2-吡啶甲醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，溶剂乙醚(2mL)和手性(R)-H8-BINOL钛全氟丁基磺酸配合物(X＝OSO2C4F9)(0.05mmol)，0℃下搅拌24h。反应结束后旋干溶剂，剩余物中用CH2Cl2萃取3次，收集固体催化剂以回收利。滤液滴入5滴三氟乙酸，搅拌30分钟。再加入2mL饱和碳酸氢钠。分液，水洗。再用20mL二氯甲烷萃取，合并萃取液。无水硫酸钠干燥，萃取液经溶剂蒸发后，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-(2-吡啶基)-2H-吡喃-4(3H)-酮。产率89％，光学产率：96％ee:determined by HPLC on Chiralcel OD column,hexane:isopropanol＝5:1,flow rate＝1mL/min,tR1＝8.50min(minor),tR2＝9.91min(major).
制备例13
在50mL圆底烧瓶中加入1-萘甲醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，溶剂四氢呋喃(2mL)和手性(R)-H8-BINOL钛全氟苯基磺酸配合物(X＝OSO2C6F5)(0.05mmol)，0℃下搅拌24h。反应结束后旋干溶剂，剩余物中用CH2Cl2萃取3次，收集固体催化剂以回收利。滤液滴入5滴三氟乙酸，搅拌30分钟。再加入2mL饱和碳酸氢钠。分液，水洗。再用20mL二氯甲烷萃取，合并萃取液。无水硫酸钠干燥，萃取液经溶剂蒸发后，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-(1-萘基)-2H-吡喃-4(3H)-酮。产率93％，光学产率：95％ee:determined by HPLC on Chiralcel OD column,hexane:isopropanol＝99:1,flow rate＝1.0mL/min,tR1＝26.71min(major),tR2＝31.68min(minor).
制备例14
在50mL圆底烧瓶中加入对硝基苯甲醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，溶剂四氢呋喃(2mL)和手性(R)-H8-BINOL钛全氟丁基磺酸配合物(X＝OSO2C4F9)(0.05mmol)，0℃下搅拌18h。反应结束后旋干溶剂，剩余物中用CH2Cl2萃取3次，收集固体催化剂以回收利。滤液滴入5滴三氟乙酸，搅拌30分钟。再加入2mL饱和碳酸氢钠。分液，水洗。再用20mL二氯甲烷萃取，合并萃取液。无水硫酸钠干燥，萃取液经溶剂蒸发后，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-(对硝基苯基)-2H-吡喃-4(3H)-酮。产率90％，光学产率：94％ee:determined by HPLC on Chiralcel OD column,hexane:isopropanol 90:10,flow rate＝1.0mL/min,tR1＝24.25min(minor),tR2＝33.82min(major).
制备例15
在50mL圆底烧瓶中加入正辛醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，溶剂四氢呋喃(2mL)和手性(R)-H8-BINOL钛全氟丁基磺酸配合物(X＝OSO2C4F9)(0.05mmol)，0℃下搅拌24h。反应结束后旋干溶剂，剩余物中用CH2Cl2萃取3次，收集固体催化剂以回收利。滤液滴入5滴三氟乙酸，搅拌30分钟。再加入2mL饱和碳酸氢钠。分液，水洗。再用20mL二氯甲烷萃取，合并萃取液。无水硫酸钠干燥，萃取液经溶剂蒸发后，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-(正辛基)-2H-吡喃-4(3H)-酮。产率85％，光学产率：91％ee:determined by HPLC on Chiralcel OD column,100:1Hexanes:isopropanol,1.0mL/min,tR1(minor)＝10.82min,tR2(major)＝11.73min)。
为了进一步体现本方法的优越性，选用以下催化体系作为对比示例：
对比例1：
在50mL圆底烧瓶中加入苯甲醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，(R)-BINOL(0.055mmol)，1.0M Ti(OiPr)4in CH2Cl2(50μL,0.05mmol)和溶剂THF(2mL)，0℃下搅拌12h。反应结束后旋干溶剂，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-(反苯乙烯基)-2H-吡喃-4(3H)-酮。产率38％，光学产率：82％ee，催化剂不能重复利用。
对比例2：
在50mL圆底烧瓶中加入苯甲醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，(R)-BINOL TiCl2(0.05mmol)和溶剂THF(2mL)，0℃下搅拌12h。反应结束后旋干溶剂，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-(反苯乙烯基)-2H-吡喃-4(3H)-酮。产率52％，光学产率：88％ee，催化剂不能重复利用。
对比例3：
在50mL圆底烧瓶中加入苯甲醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，(R)-H8-BINOL(0.055mmol)，1.0M Ti(OiPr)4in CH2Cl2(50μL,0.05mmol)和溶剂THF(2mL)，0℃下搅拌12h。反应结束后旋干溶剂，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-(反苯乙烯基)-2H-吡喃-4(3H)-酮。产率41％，光学产率：89％ee，催化剂不能重复利用。
对比例4：
在50mL圆底烧瓶中加入苯甲醛(1mmol)，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯(1.2mmol)，(R)-H8-BINOL TiCl2(0.05mmol)和溶剂THF(2mL)，0℃下搅拌12h。反应结束后旋干溶剂，得到黄色油状混合物。通过柱层析分离，得到无色油状液体(R)-2-(反苯乙烯基)-2H-吡喃-4(3H)-酮。产率62％，光学产率：90％ee，催化剂不能重复利用。
以上所述实施例仅表达了本发明的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对本发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。因此，本发明专利的保护范围应以所附权利要求为准。
Claims (9)
1.一种新型手性(R)-联萘酚钛配合物，其特征在于：所述手性(R)-联萘酚钛配合物的结构式为：
其中，阳离子由钛原子与手性(R)-联萘酚配体和两个水分子配位形成，另外两个阴离子X-与配合物的阳离子部分形成离子键。
2.根据权利要求1所述的新型手性(R)-联萘酚钛配合物，其特征在于：所述手性(R)-联萘酚配体为(R)-BINOL(BINOL：联萘酚)和(R)-H8-BINOL中的任意一种；所述X为全氟辛基磺酸基团OSO2C8F17、五氟苯基磺酸基团OSO2C6F5、全氟己基磺酸基团OSO2C6F13或全氟丁基磺酸基团OSO2C4F9中的任意一种。
3.一种权利要求1或2任一项所述的新型手性(R)-联萘酚钛配合物的制备方法，其特征在于，包括以下步骤：将手性(R)-联萘酚钛配合物二氯化物溶解于溶剂中，并在N2保护下，将银盐加入，室温下避光反应2-4h，过滤，滤液加入正己烷，直至分层，-20℃冷冻24h，析出配合物为催化剂手性(R)-联萘酚钛配合物。
4.根据权利要求3所述的新型手性(R)-联萘酚钛配合物的制备方法，其特征在于：所述溶剂为四氢呋喃、丙酮、乙腈、乙醇中的任意一种；所述银盐为全氟辛基磺酸银AgOSO2C8F17、五氟苯基磺酸银AgOSO2C6F5、全氟己基磺酸银AgOSO2C6F13或全氟丁基磺酸银AgOSO2C4F9中的任意一种；所述手性(R)-联萘酚钛配合物二氯化物与银盐的物质的量摩尔数比为1:2，每1.0mmol手性(R)-联萘酚钛配合物二氯化物用溶剂10mL。
5.一种权利要求1-4任一项所述的新型手性(R)-联萘酚钛配合物的应用，其特征在于：用作催化剂，催化反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯与醛的Hetero-Diels-Alder反应，合成手性(R)-吡喃酮化合物。
6.根据权利要求5所述的新型手性(R)-联萘酚钛配合物的应用，其特征在于：所述手性(R)-联萘酚钛配合物催化反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯与醛的Hetero-Diels-Alder反应，合成手性(R)-吡喃酮化合物的具体过程为：将醛，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯和溶剂加入反应容器中，加入手性(R)-联萘酚钛配合物作催化剂，在0-25℃下反应2-24h，反应完毕后，旋干溶剂，加入二氯甲烷萃取，过滤回收手性(R)-联萘酚钛配合物催化剂用于重复利用，滤液滴入三氟乙酸，搅拌30分钟，再加入饱和碳酸氢钠，分液，水洗，再用二氯甲烷萃取，合并萃取液，无水硫酸钠干燥，萃取液经溶剂蒸发后，得到黄色油状混合物，粗产品经柱层析分离得到手性(R)-吡喃酮化合物。
7.根据权利要求6所述的新型手性(R)-联萘酚钛配合物的应用，其特征在于，所述手性(R)-吡喃酮化合物的结构式为：
其中，R1为苯基、间甲基苯基、间甲氧基苯基、对甲氧基苯基、对氯苯基、对氟苯基、间氯苯基、对溴苯基、对硝基苯基、对氰基苯基、1-萘基、苯乙烯基、2-糠基、2-吡啶基、正庚基中的任意一种。
8.根据权利要求6所述的新型手性(R)-联萘酚钛配合物的应用，其特征在于：所述醛为苯甲醛、3-甲基苯甲醛、3-甲氧基苯甲醛、4-甲氧基苯甲醛、4-氯苯甲醛、4-氟苯甲醛、4-溴苯甲醛、糠醛、肉桂醛、3-氯苯甲醛、氰基苯甲醛、2-吡啶甲醛、1-萘甲醛、对硝基苯甲醛、正辛醛中的任意一种；所述溶剂为四氢呋喃、乙腈、二氯乙烷、乙醚、甲苯中的任意一种。
9.根据权利要求6所述的新型手性(R)-联萘酚钛配合物的应用，其特征在于：所述醛，反-1-甲氧基-3-(三甲基硅氧基)-1,3-丁二烯和手性(R)-联萘酚钛配合物的物质的量摩尔数比为1:1.2:0.05；每1mmol醛用溶剂2mL，三氟乙酸5滴，饱和碳酸氢钠2mL，二氯甲烷20mL；所述催化剂的用量为1.0-10mol％，催化剂用量以反应底物醛的摩尔数为基准；催化剂可重复利用5次以上。
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