CN1043425C - 亚水杨基氨基过渡金属配合物及其制法 - Google Patents
亚水杨基氨基过渡金属配合物及其制法 Download PDFInfo
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- CN1043425C CN1043425C CN93117792A CN93117792A CN1043425C CN 1043425 C CN1043425 C CN 1043425C CN 93117792 A CN93117792 A CN 93117792A CN 93117792 A CN93117792 A CN 93117792A CN 1043425 C CN1043425 C CN 1043425C
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 50
- -1 benzyloxy methylene Chemical group 0.000 claims description 32
- 239000001257 hydrogen Substances 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- CNFDGXZLMLFIJV-UHFFFAOYSA-L manganese(II) chloride tetrahydrate Chemical compound O.O.O.O.[Cl-].[Cl-].[Mn+2] CNFDGXZLMLFIJV-UHFFFAOYSA-L 0.000 claims description 21
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- KNWQLFOXPQZGPX-UHFFFAOYSA-N methanesulfonyl fluoride Chemical compound CS(F)(=O)=O KNWQLFOXPQZGPX-UHFFFAOYSA-N 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 229940045641 monobasic sodium phosphate Drugs 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- FQGYBKCWOANXHP-UHFFFAOYSA-N oxolan-2-yl methanesulfonate Chemical compound CS(=O)(=O)OC1CCCO1 FQGYBKCWOANXHP-UHFFFAOYSA-N 0.000 description 1
- VPSJSRRUXSUNFA-UHFFFAOYSA-N oxolane-3,4-diamine Chemical compound NC1COCC1N VPSJSRRUXSUNFA-UHFFFAOYSA-N 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 229960003487 xylose Drugs 0.000 description 1
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Abstract
一种通式(Ⅰ)的化合物
其中M是过渡金属离子;
必要时,A是抗衡离子。
Description
本发明涉及一种新催化剂和它们在某些烯烃转化为手性富集环氧化物中的应用。
其中:
M是过渡金属离子,A是阴离子,n是0、1或2。X1或X2中至少一个是选自由硅烷基、芳基、仲烷基和叔烷基组成的组;X3或X4中也至少一个是选自相同的组。Y1、Y2、Y3、Y4、Y5和Y6独立地选自由氢、卤素、烷基、芳基、硅烷基、和带有如烷氧基和卤素的杂原子的烷基组成的组。R1、R2、R3和R4中至少一个选自由H、CH3、C2H5和伯烷基组成的第一组。如果R1选自第一组,则R2和R3选自由芳基、带有杂原子的芳香基、仲烷基和叔烷基组成的第二组。如果R2选自第一组,则R1和R4选自第二组如果R3选自第一组,则R1和R4选自第二组。如果R4选自第一组,则R2和R3选自第二组。
这样的催化剂可以用在前手性烯烃的对映选择环氧化上。
制备了一种结构上完全不同的催化剂,它们出人意料地具有对某些前手性烯烃的对映选择环氧化作用的催化能力。
A必要时是抗衡离子;
r、s和t分别是0-3,以使得r+s+t在1-3的范围内;
Ra、Rb、Rc分别是氢或CH2OR′,这里R′是氢或有机基团;
B和E分别是氧、CH2、NRd,这里Rd是烷基、氢、烷羰基、或芳羰基或SOn,n是0或整数1或2,前提是B和E不能同时是CH2,当B是氧、NRd或SOn时,则r不能为零,当E是氧、NRd或SOn时,则t不能为零;
R1、R2、R3、R4、R5、R6、R7、 R8、R9和R10分别是H、烷基或烷氧基;
合适的过渡金属离子M包括处于适当氧化状态的Mn、Cr、Fe、Ni、Co、Ti、V、Ru和Os。
优选的过渡金属离子M是二价或三价的Mn。
应当理解在某些情况下,如当M是Mn(Ⅱ)时,不需要抗衡离子。
合适的抗衡离子A包括WO91/14694中提到的阴离子。
优选的A是氯。
合适的有机基团R′包括烷基、烷羰基、芳羰基或芳基衍生基团。
特别的R′基团实例包括取代烷基。
R′的一个实例是三苯甲基。
优选的s和t是零,r是1,Ra是氢,B是氧,E是CH2;或者r、s和t都是1,Ra、Rb和Rc是氢,B和E都是氧,或者s为零,r和t都为1,Ra是氢或三苯甲氧基亚甲基,Rc是氢,B是氧,E是-CH2-;或者r、t都是1,s是零,Ra和Rc是氢,B是NRd,这里Rd是苯基羰基,E是CH2。
合适地,R2、R4、R5和R7都代表氢。
合适地,R1、R3、R6和R8分别为C1-6烷基。
特别地,R1和R8是支链烷基,如叔烷基。
R3和R6有利的也是支链烷基。
R1和R6的一优选实例是叔丁基。
R3和R6的特殊实例是叔丁基和甲基。
R2、R4、R5和R7的实例是氢。
当单独使用或作为其它基团的一部分(如烷氧基或烷羰基)时,术语“烷基”包括直链或支链烷基,它们含有1-12个碳原子,合适的是1-6个碳原子,例如,包括甲基、乙基、正丙基、异丙基、正丁基、异丁基或叔丁基。
在这里使用的术语“芳基”包括任意地被多至5个,优选的是多至3个,选自由卤素、烷基、苯基、烷氧基、卤烷基、烷羰基、苯羰基组成的组的基团所取代的苯基和萘基。
一个优选的芳基是取代或非取代苯基。
过渡金属M包括那些具有氧化态为(Ⅱ)或更高的金属。
合适的芳基的取代基包括烷基、卤素和烷氧基。
可选的烷基的取代基包括这里提到过的芳基的取代基,苯基是一特例。
应当理解,带有标记“*”(星号)的碳原子是手性中心,而本发明包括任何单个的对映体和它们的任何混合物。
本发明还提供了一种通式(Ⅰ)化合物的制备方法,它包括形成如下通式(Ⅱ)的化合物的过渡金属的络合物:其中可变的R1至R10、B、E、r、S、t、Ra、Rb和Rc都按通式(Ⅰ)的定义,如有必要,可以是据此分离的任何对映体。
合适地,过渡金属离子的络合物可以在提高的温度下,通过向处于合适溶剂如乙醇或二氯甲烷中的通式(Ⅱ)的化合物添加合适的过渡金属盐,如醋酸锰(Ⅱ)或(Ⅲ),优选的是醋酸锰(Ⅲ),来形成。任选的抗衡离子的置换或互变都可以通过加入含有所需的抗衡离子的碱金属盐如LiCl来进行。
任何对映体的分离都可以通过传统的技术如衍生物的结晶或色谱法来完成。然而应当理解,对映体分离最好是在过渡金属络合物形成之前完成。
本发明进一步提供了一种通式(Ⅱ)的化合物的制备方法,其中包括以任何顺序逐步使通式(Ⅲ)的化合物:其中r、s、t、Ra、Rb和Rc、E、B都如通式(Ⅰ)的定义,而R11、R12单独代表氢或氨保护基团,R11和R12中至少一个是氢,与通式(Ⅳ)的化合物和通式(Ⅴ)的化合物缩合,并在必要时去除任何保护基团R11和R12,
其中R1至R10都按通式(Ⅰ)的定义,此后,按需要分离所需的化合物,包括必要时分离任何对映体。
通式(Ⅱ)的化合物优选的是从通式(Ⅲ)的旋光纯化合物制备,而通式(Ⅲ)的化合物优选的是从其旋光纯起始原料制备。通式(Ⅱ)或(Ⅲ)的化合物对映体的外消旋物或混合物可以应用本领域内的常规技术如衍生物的结晶或色谱法来把它们拆分。
当所需的通式(Ⅱ)的化合物中,R1、R2、R3、R4和R9有一个或多个与R8、R7、R6、R5和R10中的一个或多个分别不相同时,则通式(Ⅲ)化合物可以通过在惰性溶剂如乙醇中加热通式(Ⅲ)的有适当保护的化合物与通式(Ⅳ)或通式(Ⅴ)的化合物(摩尔比1∶1),以任何顺序分步缩合,必要时,可以提纯得到的通式(Ⅵ)或(Ⅶ)的中间化合物:其中可变的R1-R12、r、s、t、Ra、Rb、Rc、E和B都如通式(Ⅲ)、(Ⅳ)和(Ⅴ)中定义,提纯是应用常规的技术如色谱法来去除任何R11或R12的保护基团,当需要时,使用通式(Ⅳ)或(Ⅴ)的化合物重复这些反应。
合适的保护基团R11或R12包括常规的胺保护基团,如苄基、硅烷基或酰基,如苯甲酰基。
代表保护基团的R11或R12的去除可以根据保护基团的性质用本领域内的常规技术来完成。
应当理解。当R1、R2、R3、R4和R5中的每一个与R8、R7、R6、R5和R10的每一个分别相同时,则通式(Ⅳ)和(Ⅴ)的化合物也相同,因此,在惰性溶剂中,在提高的温度下,如在回流条件下,优选地应用其中R11或R12是氢的通式(Ⅲ)的化合物和二摩尔的通式(Ⅳ)或(Ⅴ)的化合物。
通式(Ⅲ)的化合物可以是已知化合物,或者按已知的方法或类似已知的方法或这里描述的类似的方法制备的化合物,如当通式(Ⅲ)的化合物是3,4-二氨基四氢呋喃时,该化合物可按下述方案,例如描述例1和2中所描述的方法来制备。
5R,6R-二氨基-1,3二噁庚环(dioxepane)可按描述例8-13所描述的步骤制备。
3R,4S-二氨基四氢吡喃可以按描述例15-17所描述的步骤来制备。
3R,4R-二氨基-(2 R)(三苯基甲氧基甲基)四氢呋喃可以按描述例21-24所描述的步骤来制备。
(±)反-1-苄氧基-3,4-二氨基哌啶可以按描述例25-27所描述的步骤制备。
通式(Ⅳ)和(Ⅴ)的化合物可以是市场上买到的,或者已知的化合物,或者按已知的方法或类似已知的方法,如G.Casiraghi等人在J.(Them.SOC.Perkin Transaction I.1980 P1862-1865中描述的方法制备的。
通式(Ⅱ)、(Ⅲ)、(Ⅳ)、(Ⅴ)、(Ⅵ)和(Ⅶ)的新化合物构成了本发明的一个方面。
应当理解,术语手性催化剂指对某一种对映体有优势的通式(Ⅰ)的催化剂,因此,它在从前手性烯烃生产环氧化物时可用来形成某种特殊对映体的优势。
应当理解,通式(Ⅰ)的催化剂优选地以手性形式通过使用已拆分的可用传统技术拆分的通式(Ⅲ)的化合物来制备。通式(Ⅲ)的化合物本身可以通过适当的前体来制备,这些前体,如前面论述过的可以用传统技术拆开或可以拆开形式购买到。此外,通式(Ⅱ)的偶合的化合物可以传统技术拆分。
本发明还进一步提供一种在有氧气源和通式(Ⅰ)的手性催化剂存在的条件下对映选择地环氧化前手性烯烃的方法。
合适的前手性烯烃包括含有下述基团作为它们的一部分结构的化合物,环乙烯、5,6-二氢-2H-吡喃、1,2,5,6-四氢吡啶、1,2,3,4-四氢吡啶和5,6-二氢-2H-噻喃。
有利的前手性烯烃包括这些化合物,它们的部分结构形式为如下基团:1,2-二氢萘、2 H-苯并吡喃、1,2-二氢喹啉,1,2-二氢异喹啉和2H-1,2苯并硫吡喃。
这些化合物在钾通道(Channel)活化剂领域内是众所周知的。
优选地,前手性烯烃包括EP-A-0376524中提到的那些烯烃,如那里的通式(ⅩⅣ)的化合物,特别是2,2-二甲基-6-五氟乙基-2H-1-苯并吡喃。
应当理解,本发明特别延伸到用这里所述的方法制备通式(Ⅰ)的化合物特别是其特例用的EP-A-0376524中所有的环氧化物前体。
本发明还特别延伸到再把所有环氧化前体转化成EP-A-0376524中的特殊实例,在这些特殊实例中特别是制备(-)反-3,4-二氢-2,2-二甲基-4-(2-氧代哌啶-1-基)-6-五氟乙基-2H-1-苯并吡喃-3-酚。
合适的氧源包括次氯酸钠。
应当理解,生产EP-A-0376524中描述的化合物的环氧化物前体的3S,4S对映体,只需要通式(Ⅰ)的催化剂的一种对映体,这种对映体再生产EP-A-0376524中描述的通式(Ⅰ)的化合物的3S,4R构型。与之相对应,环氧化物前体的3R,4R对映体用来生产EP-A-0376524中描述的通式(Ⅰ)的化合物的3R,4S构型。
下面用描述例和实施例详细说明本发明。描述例1:(±)2,5-二氢-3-硝基呋喃(D1)
在CH2Cl2(2.2L)中的(±)反3-氯汞基-4-硝基-2,5-二氢呋喃1(38.54g,109.6mmol)和Et3N(11.07g,109.6mmol)的混合物在25℃下搅拌1.25h。加入5%的柠檬酸水溶液(1.1L),继续搅拌5min。通过硅藻土过滤混合物,分离后,有机相用5%柠檬酸水溶液(220ml)洗涤,在Na2SO4上干燥,真空浓缩,在用CHCl3-已烷(1∶1->1∶0)洗脱的硅胶(Merck 9385,300g)上用色谱法提纯残留物,得到冷冻结晶的浅黄色油(D1),5.45g(43.2%)。
δ(CDCl3)4.95(4H,S)和7.10(1H,S)
1.P.Bitha和Y-I Lin,J.Heterocyclic Chem.,1985,25,1035-1036。描述例2:(±)3,4-二氨基四氢呋喃(D2)
用经由Bitha和lin1的方法(用DI)制得的(±)4-氨基-3-硝基四氢呋喃(4.66g,35.3mmol)的EtOH(100ml)的溶液,其中包含有载有10%的钯的碳(2.5g),在Parr摇动设备上,在35psi压力下,在25℃加氢65h。过滤悬浮液,用EtOH(100ml)洗涤固体,收集的滤液在真空下蒸发,得到(±)(D2)的无色油,3.26g(81.5%)。
δ(CDCl3)1.40(4H,b5),3.20(2H,m),3.50(2H,dd)和4.08(2H,dd)。描述例3:
(±)3,4-双(3-权丁基-5-甲基亚水杨基氢基(Sal-icylideamino))四氢呋喃(D3)
将外消旋二胺(D2)(855mg,8.38mmol)和3-权丁基-5-甲基水杨醛(3.22mg,16.76mmol)的EtoH(50ml)溶液加热回流1.5h。真空除去溶剂,在用CHCl3作洗脱剂的硅胶(Merck 9385,300g)上用色谱是纯残留物,得到浅黄针状物(±)(D3),13.5g,(35.8%)
δ(CDCl3)1.42(18H,S),2.25(6H,S),3.95-4.10(2H,M),4.43(2H,g),6.90(2H,d),7.15(2H,d),8.30(2H,S)和13.10(2H,bS)。描述例4:(S,S)反3,4-双(甲磺酰氧基)四氢呋喃(D4)
在THF(75ml)和Et2O(75ml)混合物中的1,4-脱水-L-threitol(2.45g,23.5mmol,从Aldrich Chemical公司购得)溶液在0℃下分步用三乙胺(7.2ml,51.7mmol,2.2eq)和甲磺酰氧(3.82ml,49.35mmol,2.1eq)处理。混合物搅拌4h,再在0℃存放过夜(-16h)。
反应物过滤,用THF(20ml)洗涤固体。收集的滤液在真空下蒸发,再在10%的柠檬酸水溶液(60ml)和EtOAC(150ml)之间分配。干燥(MgSO4)并蒸发有机相,得到无色油(D4),5.82g(95%)。
δ(CDCl3)3.12(6H,S)4.00(2H,dd),4.18(2H,dd)和5.25(2H,dd)。描述例5:(S,S)反3,4-二叠氮基四氢呋喃(D5)
在DMSO(60ml)中的二甲磺酰酯(D4)(5.80g,22.3mmol)和锂的叠氮化物(5.46g,111.5mmol,2.5eq)的混合物在100-110℃下加热40h。冷却至室温后,用水(IL)稀释反应物,并用EtoAC(IL,2×0.75L)萃取。用水(0.5L)和盐水(0.5L)洗涤收集的有机相,在MgSO4上干燥,并真空蒸发,得浅黄色油状的标题化合物,2.18g(61.5%)。
δ(CDCl3)3.75(2H,dd)和3.90-4.05(4H,m)。描述例6:(S,S)反3,4-二氨基四氢呋喃
在0℃下,往无水THF(150ml)中的氢化锂铝(2.05g,54mmol)中,在10min内滴加在THF(50ml)中的二叠氮化合物(D5)(2.08g,13.5mmol)。15min后溶液升温至室温,再搅拌16h。
反应混合物再冷却至0℃,分步用水(2ml),15%的NaOH水溶液(2ml),再用水(6ml)骤冷,再升温至室温、搅拌1h后用硅藻土过滤混合物,用THF(2×150ml)漂洗,收集滤液,真空蒸发,得浅黄色油(D6),1.28g(93%)。
δ(CDCl3)1.30(4H,bS),3.20(2H,dd),3.50(2H,dd)和4.08(2H,dd)。描述例7:(S,S)反3,4-双(3-叔丁基-5-甲基亚水杨基氨基)四氢呋喃(D7)
将(S,S)-二胺(D6)(1.26g,12.35mmol)和3-叔丁基-5-甲基水杨醛(4.74g,24.70mmol)的EtOH(75ml)溶液加热回流3.5h。冷却溶液,真空去除溶剂得黄色油状粗产品(5),5.50g(99%)。
粗产品(4.55g)的试样在硅胶(Merck 9385,含CHCl3的己烷梯度洗脱)得纯的黄色泡沫体(D7),4.39g(95.5%产率)。
δ(CDCl3)1.42(18H,S),2.25(6H,S),3.95-4.10(4H,M),4.33(2H,q),6.90(2H,d),7.15(2H,d),8.30(2H,S)和13.15(2H,bs)。描述例8:
(2R,3R)-1,4-二苯氧基-2,3-二甲磺酰氧基丁烷
向在冰浴中冷却的(2R,3R)-(+)-1,4-二苯氧基-2,3-丁二醇(25.3g,83.7mmol,自Aldrich Chemical公司购得)的二氧甲烷(165ml)溶液中添加甲磺酰氧(13.0ml,167.4mmol),再缓慢添加三乙基胺(23.3ml,167.4mmol),温度不超过5℃。添加完毕后,在有冰浴冷却的情况下搅拌反应物3h。加入水(600ml),分离有机相。再用二氯甲烷(200ml)萃取水相,收集有机相,用水(400ml)和盐水(400ml)洗涤有机相,干燥(MgSO4)蒸去溶剂得浅黄色固体。用***研制得标题化合物(28.2g,74%)的无色结晶,m.p.72-73℃。
1Hn.m.r.(CDDl3):δ3.03(S,6H,2×CH3),3.76(m,4H,2×CH2O),4.48(d,2H,CH2ph),4.57(d,2H,CH2ph),5.00(m,2H,2×CH),7.29-7.39(m,10H,2×ph)。
13Cn,m.r.(CDDl3):δ38.8(2×CH3),68.7(2×CH2),73.7(2×CH2),78.7(2×CH),128.1,128.2,128.6,137.0(2×Ph)。
EI-MS:m/e 459(MH+),367(M+-CH2Ph)。C20H25D8S2计算值:C:52.39,H:5.72%。
实验值:C:52.36,H:5.59%。描述例9:(2R,3R)-二甲磺酰氧基丁烷-1,4-二醇
把(2R,3R)-1,4-二苯氧基-2,3-二甲磺酰氧基丁烷(27.6g,60.3mmol)(D8)溶解在丙酮(500ml)中,添加10%Pd/C(29.9g)的丙酮(300ml)悬浮液,混合物在1atm压力和环境温度下加氢2h。用硅石和硅藻土填充物把混合物过滤三次,蒸去溶剂,得到稻草色的油状标题化合物(14.7g,87%),该油状物存放即固化。
1Hn.m.r.(DMSO-d6):δ3.24(S,6H,2×CH3),3.69(m,4H,2×CH2),4.76(m,2H,2×CH),5.33(t,2H,2×OH)。
13Cn,m.r.(DMSO-d6):δ38.1(2×CH3),59.7(2×CH2),80.3(2×CH)。
EI-MS:m/e279(MH+),261(M+-H2O),183(M+-OMs),165(M+-OMs,H2O)。描述例10:(6R,7R)-二甲磺酰氧基-2,4,9,11-四噁十二烷
将(2R,3R)-二甲磺酰氧基丁-1,4-二醇(14.7g,52.9mmol)(D9)溶解在40℃的二甲氧基甲烷(89.5ml)和二氯甲烷(30ml)中。添加溴化锂(0.91g)和对甲苯磺酸的一水合物(1.01g,5.29mmol),混合物加热回流3h,反应物冷却至室温,再注入饱和碳酸氢钠溶液(200ml),用乙酸乙酯(2×200ml)萃取,干燥(MgSO4)、蒸发得无色油。在硅胶下用柱色谱法纯化,并用含0-1%甲醇的二氯甲烷洗脱,得标题化合物的无色油(8.2g,42%)。
1Hn.m.r.(CDCl):δ3.13S,6H,2×CH3),3.39(S,6H,2×OCH3),3.87(m,4H,2×CH2),4.66(m,4H,2×OCH2O),5.20(m,2H,2×CH)。
13Cn,m.r.(CDCl3):δ38.8(2×SCH3),55.8(2×OCH3)66.1(2×CH2),78.4(2×CH),96.8(2×OCH2O)。
CI-MS:m/e384(MNH4 +)。C10H22O10S2计算值:C:32.78,H:6.05%。
实验值:C:32.22,H:5.62%。描述例11:(5R,6R)-二甲磺酰氧基-1,3-二噁庚环
将(6R,7R)-二甲磺酰氧基-2,4,9,11-四噁十二烷(8.2g,22.4mmol)(D10)和对甲苯磺酸一水合物(0.26g,1.34mmol)的甲苯(165ml)溶液加热回流过夜,蒸去溶剂,棕色残留物用***研制得标题化合物的米白色固体(5.9g,91%)M.P.133-134℃。
1Hn.m.r.(CDCl3):δ3.13(S,6H,2×CH3),3,84(m,2H,CH2),4.06(m,2H,CH2),4.77(S,2H,OCH2O),4.81(m,2H,2×CH)。
13Cn,m.r.(CDCl3):δ38.8(2×CH3),64.1(2×CH2),78.3(2×CH),94.6(OCH2O)。
EI-MS:m/e 291(MNH+),195(M+-OMs)。C7H14O8S2计算值:C:28.96,H:4.86%。
实验值:C:29.22,H:4.61%。描述例12(5R,6R)-二叠氮基-1,3-二噁庚环
在二甲基亚砜(60ml)中的(5R,6R)-二甲磺酰氧基-1,3-二噁庚环D11(5.0g,17.2mmol)和锂的叠氮化合物(4.2g,86mmol)的混合物加热至110-120℃搅拌过夜。冷却混合物,注入水(200ml)中,用乙酸乙酯(2×150ml)萃取。收集有机相,用水(2×150ml)和盐水(150ml)洗涤,干燥(MgSO4),蒸发,得标题化合物的棕色油(2.7g,85%)。
1Hn.m.r.(CDCl3):δ3.49(m,2H,2×CH),3.74(m,2H,2×CH2),3.93(m,2H,CH2),4.73(S,2H,OCH2O)。
13Cn,m.r.(CDCl3):δ64.3(2×CH),64.6(2×CH2),94.3(OCH2O)。EI-MS:m/e185(MH+),157(MH+-N- 2),142(M+-N3)。C5H6N6S2计算值:C:32.61,H:4.38,N:45.63%。
实验值:C:32.33,H:4.67,N:45.38%。描述例13:(5R,6R)-二氨基-1,3-二噁庚环
在0℃和氩气氛中,向氢化锂铝(2.1g,55.3mmol)无水四氢呋喃(70ml)浆液中滴加(5R,6R,)-二叠氮基-1,3-二噁庚环(2.6g,14.1mmol)(D12)的无水四氢呋喃(50ml)溶液。添加过程中,反应温度用冰一盐浴保持在10℃以下。反应完成后,反应混合物升温至室温,再进一步搅拌1.5h。然后再冷却,并用水(2ml),2M NaOH(2ml)和水(4ml)骤冷,用冰一盐浴再把温度维持在10℃以下。骤冷后的反应物再升温至室温,再搅拌2h,然后,用硅藻±和用四氢呋喃洗好的过滤填料过滤,收集滤液,蒸发浓缩,得标题化合物的浅黄色油(1.3g,70%)。
1 Hn.m.r.(CDCl3):δ1.56(6rs,4H,2×NH3),2.62(m,2H,2×CH),3.58(m,2H,CH2),3.77(m,2H,2×CH2),4.72(S,2H,OCH2O)。
13Cn,m.r.(CDCl3):δ57.9(2×CH),67.5(2×CH2),93.8(OCH2O)。C5H12N2O2计算值:C:45.44,H:9.15,N:21.20%。
实验值:C:45.13,H:8.76,N:19.58%。
EI-MS:m/e133(MH+),116(M+-NH2)+,90(M-2NH2)+。描述例14:制备(5R-6R)-二-(3,5-二叔丁基)亚水杨基氨基-1,3-二噁庚环
把(5R,6R)-二氨基-1,3-二噁庚环(1.0g,7.6mmol)(D13)和3,5-二叔丁基水杨醛(3.6g,15.4mmol,2eq)溶解在乙醇(100ml)中,溶液搅拌回流3h。然后使反应混合物冷却,蒸去溶剂,用硅胶柱色谱纯化残流物,并用含4%***的己烷洗脱。得标题化合物的鲜黄色泡沫体(3.5g,82%)。
1 Hn.m.r.(CDCl3):δ1.23(S,18H,6×CH3),1.41(S,18H,6×CH3),3.85(m,2H,CH2),4.07(m,2H,CH2),4.87(S,2H,OCH2O),6.99(d,2H,Ar),7.33(d,2H,Ar),8.33(S,2H,2×CH=N),13.20(drs,2H,2×OH)。
13Cn,m.r.(CDCl3):δ29.4(6×CH3),31.4(6×CH3),34.1(2×CCH3),35.0(2×CCH3),67.7(2×CH),73.8(2×CH2),94.2(OCH2O),117.6,126.4,127.4,136.6,140.3,157.9(Ar),168.4(2×C=N)。C35H52N2O4计算值:C:74.43,H:9.28,N:4.96%。
实验值:C:74.56,H:9.15,N:4.92%。CI-MS:m/e565(MH+)。描述例15:(3R,4R)-二乙酰氧基四氢吡喃(D15)
在大气压和25℃下,氢化含有PtO2(400mg)的3,4-二-O-乙酰基-D-木糖醛(11.16g)的50%乙醇水(400ml)溶液3.5h。用硅藻土过滤悬浮液,再用50%乙醇水溶液(50ml)和水(50ml)洗涤,收集滤液,真空浓缩,得标题化合物的无色油,9.6g(85%)。
δ(CDCl3):1.30-1.50(1H,m),2.10(6H,S),2.10-2.20(1H,m),3.35-3.60(2H,m),3.80-4.00(2H,m)和4.80-5.00(2H,m)。2,《有机化合物词典》,第5版,1982,Chapmar & Hall,London,579和其参考资料。描述例16:(3R,4R)-二甲磺酰氨基四氢吡喃(D16)
在室温下将钠(-50mg)溶解于甲醇100ml)中。向该溶液中添加二酯(D15)(9.56g,47.3mmol)的甲醇(100ml)溶液,混合物搅拌72h。再加入AmberLite IR 120H+树脂(20g),过滤混合物。真空浓缩滤液,得无色油状二醇。把二醇溶解于四氧呋喃(220ml)和二***(220ml)混合液中。加入三乙胺(10.86g,107.5mmol),溶液冷却至0℃。在0℃滴加甲磺酰氟(11.76g,102.7mmol),溶液再搅拌1小时,再在4℃存放16h。过滤悬浮液,用四氢呋喃(2×95ml)和二***(2×180ml)洗涤固体;真空蒸发收集的滤液,残留物在乙酸乙酯(200ml)和10%柠檬酸水溶液(200ml)之间分配。有机相经干燥(MgSO4)、过滤、真空浓缩得标题化合物的无色泡沫体12.07g(93%)。
δ(CDCL3):3.10(6H,S),2.00-2.40(2H,m),3.40-4.20(4H,m),4.55-4.65(1H,m),和4.70-4.85(1H,m)。描述例17:(3R,4S)-二氨基四氨吡喃(D17)
将二甲磺酰酯(D16)(12.07g,44mmol)溶解于二甲亚砜(88ml)中,用锂的叠氮化物(10.8g,220mmol)处理。混合物在100℃下加热40h,冷却至室温,注入水(1.03L)中,用乙酸乙酯萃取(1.03L,2×0.59L)。收集的有机相用水(300ml)和盐水(300ml)洗涤,在MgSO4上干燥,真空浓缩,得棕色油状的粗二叠氮化物3.7g。将这些化合物溶解于四氢呋喃(45ml)中,再滴加到冷的(0℃)氢化锂铝(3.34g,88mmol)的四氢呋喃(220ml)悬浮液中,并维持温度低于10℃。添加完毕后,在0℃搅拌悬浮液0.5h,再升温至室温搅拌16h。
混合物再冷却至0℃,并用含水(3.34ml)的四氢呋喃(5ml)、15%的氢氧化钠水溶液(3.34ml)和水(10ml)骤冷。混合物再升温至室温,搅拌1h,尔后用硅藻土过滤,用四氢呋喃(2×400mml)漂洗。将收集的滤液真空浓缩得无色油状标题的二胺(3),2.62g(51%)。
δ(CDCL3):1.20-1.90(6H,m),2.40-2.50(2H,m),2.90-3.40(2H,m)和3.80-4.00(2H,m)。描述例18:(3R,4S)-双-(3.5-二叔丁基亚水杨基氨基)四氢呲喃,(D18)
向含有二胺(D17)(2.55g,22mmol)的乙醇(220ml)中添加3.5-二叔丁基水杨醛(10.3g,44mmol)。混合物回流加热2h,冷至室温,真空干燥结晶产品,得黄色结晶标题化合物,4.81g(40%)。
δ(CDCl3):1.20(18H,S),1.40(18H,S),1.50-2.20(2H,m),3.50-3.70(4H,m),4.00-4.15(2H,m),7.00(2H,bs),7.35(2h,bs),8.33(1H,S),8.37(1H,S)和13.20(2H,bs)。描述例19:(3R,4S)-双-(3-叔丁基-5-甲基亚水杨基氨基)四氢吡喃(D19)。
将二胺(D17)(0.62g,5.35mmol)和3-叔丁基-5-甲基水杨醛(2.05g,10.7mmol)的乙醇(40ml)溶液加热回流2h。冷却溶液再在4℃存放70h,得黄色沉淀物。过滤,用冷95%乙醇水溶液(5ml)洗涤,真空干燥,得标题化合物,1.22g(49%)。
δ(CDCl3):1.4b(18H,S),1.80-2.20(2H,m),2.20(6H,s),3.40-3.70(4H,m),4.00-4.20(2H,m),6.80(2H,bs),7.05(2H,bs),8.27(1H,S),8.30(1H,S)和13.30(2H,bs)。描述例20:(3S,4S)-双(3,5-二叔丁基亚水杨基氨基)四氢呋喃(D20)
将(S,S)-二胺(D6)(0.96g,9.4mmol)和3,5-二叔丁基水杨醛(4.4g,18.8mmol)的乙醇(90ml)溶液加热回流2h。混合物冷却至0℃,过滤,用冷乙醇洗涤固体物并干燥,得到标题化合物的黄色晶体,3.07g(61%)。δ(CDCl3):1.27(18H,S),1.45(18H,S),3.95-4.10(4H,m),4.30-4.40(2H,m),7.05(2H,d),7.40(2H,d),8.35(2H,S)和13.20(2H,S)。描述例21:(3S,4R)-二羟基-(2R)-(羟甲基)四氢吡喃(D21)
D-己烯糖(16.0g,0.11mmol)的50%乙醇水(500ml)溶液用氧化铂(0.75g)处理,并在室温和大气压下加氢5h。悬浮液用木炭(50g)处理,通过硅藻±(200g)过滤,固体用50%乙醇水溶液(300g)洗涤。收集的滤液在真空下蒸发,在P2O5上干燥,得无色油状标题化合物,16.0g(99%)。
δ(CDDCl3):1.50-1.70(1H,m),1.80-2.20(1H,m),3.00-3.20(2H,m),3.30-3.70(3H,m),3.80-4.00(2H,m)和4.90(3H,bs)。3、《有机化合物词典》,第5版,1982,Chapman和Hall London,2754,和其参考资料。描述例22:(3S,4R)-二羟基-(2R-)-(三苯基甲氧基甲基)四氢吡喃(D22)
用三苯甲基氯(3.31g,11.9mmol)和4-(二甲基氨基)吡啶(50mg)处理三醇(D21)(17.6g,11.9mmol)的吡啶(20ml)溶液。加入二异丙基乙基胺(1.92g,14.8mmol,1.25eq),溶液在室温下搅拌4h。
把混合物注入水(200ml)中,用二***萃取(2×200ml)。收集的有机相用10%柠檬酸水溶液(100ml)和盐水(100ml)洗涤,在MgSO4上干燥,并真空浓缩成油。残留物在硅胶(洗脱剂:含甲醇的氯仿梯度洗脱剂)上用色谱法提纯,得无色泡沫体的标题化合物,3.70g(79.7%)
δ(CDDCl3):1.60-1.80(1H,m),1.90-2.00(1H,m),2.70(2H,bs,D2Oexch),3.25-3.50(5H,m),3.60-3.70(1H,m),3.90-4.00(1H,m)和7.20-7.50(15H,m)。描述例23:(3R,4R)-二甲磺酰氧基-(2R)-(三苯甲氧基甲基)四氢吡喃(D23)
向二***和四氢呋喃(2∶1,150ml)的混合物中的二醇(D22)(3.10g,7.95mmol)中添加三乙胺(1.76g,17.5mmol)。混合物冷至0℃,加入甲磺酰氯(1.91g,16.7mmol)。2h后,过滤悬浮液,真空浓缩滤液,然后再溶解在乙酸乙酯(200ml)中。溶液用10%柠檬酸水溶液(100ml)和盐水(50ml)洗涤。再在MgSO4上干燥。真空去除溶剂,干燥残留物,得(12)无色固体,4.25g,(95%)。
δ(CDDCl3):2.20-2.50(2H,m),2.50(3H,m),3.10(3H,s),3.20-3.30(1H,m),3.40-3.60(3H,m),3.95-4.10(1H,m)4.70-4.80(2H,m)和7.20-7.50(15H,m)。描述例24:(3S,4S)-双(3.5-二叔丁基亚水杨基氨基)-(2R)-三苯甲氧基甲基四氢吡喃(D24)
使二甲亚砜(20ml)中的二甲磺酰酯(D23)(2.85g,5.22mmol)和锂的叠氮化物的混合物在100-110℃下加热24h。冷却溶液,注入水(200ml)中,用乙酸乙酯(2×300ml)萃取。收集的有机相用水(2×300ml)和盐水(300ml)洗涤,在MgSO4上干燥,去除溶剂,得二叠氮中间产物的黄色泡沫体(1.52g)。
在0℃将含1.40g的一份二叠氮化物的四氢呋喃(10ml)加入到含氢化锂铝(470mg),12.4mmol)的四氧呋喃(30ml)悬浮液中,在0℃搅拌1h后,混合物升温至室温,再搅拌16h。悬浮液再冷却至0℃,分别用水(0.5ml)、15%氢氧化钠水溶液(0.5ml)、水(1.5ml)骤冷。升温至室温并搅拌1h后,过滤混合物,用四氢呋喃(2×20ml)洗涤固体,蒸发收集的滤液得粗二胺的泡沫体(1.28g)。
将乙醇(30ml)中的一份二胺(1.18g)和3.5-二叔丁基水杨醛(1.42g,6.08mmol)加热回流4h,再冷至室温,真空去除溶剂,在硅胶上(洗脱剂:含氧仿的已烷梯度洗脱剂)用色谱法提纯残留物得黄色粉未状标题化合物210mg,从(D23)的总收率为8.4%。
δ(CDCl3):1.25(9H,m),1.30-1.60(2H,m),1.32(9H,S),1.40(9H,S),1.50(9H,S),2.40-2.55(1H,S),2.70-2.80(1h,S),3.30-3.60(2H,m),3.90-4.30(3H,m)6.85(1H,bs),7.00-7.35(16H,m),7.38(1H,bs),7.45(1H,bs)8.30(1H,s),8.50(1H,bs),13.25(1H,S)和13.50(1H,S)。描述例25:(±)反-1-苯甲酰基-3,4-双(甲磺酰氧基)哌啶(D25)
将(±)反-1-苯甲酰基哌啶-3,4-二醇(3g,13.6mmol)悬浮在二氧甲烷(70ml)中,加入三乙胺(5.74ml,43mmol)。混合物冷至-10℃,在5min期间加入甲磺酰氯(2.6ml,34mmol)。过15min后,将混合物注入冰水(50ml)中,用15%的柠檬酸水溶液(30ml)洗涤有机相。溶液经在MgSO4上干燥、真空浓缩得泡沫体,5.3g(100%)。
δ(CDCl3):1.95(2H,m),2.30(2H,m),3.15(6H,S),4.70(2H,m),4.85 2H,m)和7.45(5H,m)。4,V.Petrow和0.Stepehnson,J Pharm.Pharmacol,1962,14,360-314。描述例26:(±)反-1-苯甲酰基-3,4-二叠氨基哌啶(D26)
将二甲亚砜(36ml)中的二甲磺酰酯(D25)(5.3mg,14mmol)和锂的叠氮化物(3.4mg,69mmol)的混合物在100℃加热回流18h。冷却后,反应混合物在二氯甲烷(200ml)和水(50ml)之间分配。分离出水相,用二氯甲烷(100ml,50ml)萃取,收集的有机萃取液用水(3×50ml)洗涤,在MgSO4上干燥并真空浓缩。残留物在硅胶(洗脱剂:含甲醇的二氯甲烷梯度洗脱剂)上用色谱法提纯,得标题化合物的无色固体,900mg(24%)。
δ(CDCl3):1.60(2H,m),2.10(2H,m),3.05(2H,m),3.20(2H,m)和7.40(5H,m)。描述例27:(±)反-1-苯甲酰基-3,4-二氨基哌啶(D27)
二叠氨(D26)(450mg,1.7mmol)的乙醇(30ml)溶液用Lind-lar催化剂(5%pd/CaCO3,250mg)处理,在氢气(1atm)中搅拌24h。过滤混合物,真空去除溶剂得油状标题化合物,350mg(94%)。
δ(CDCl3):1.20(1H,m),1.65-1.80(2H,m),2.20(2H,m),2.70(1H,m),3.00(1H,m),3.30(1H,m),4.40(2H,m)和7.40(5H,m)。描述例28(-)反-l-苯甲酰基-3,4-双(3,5-二叔丁基亚水杨基氨基)哌啶(D28)
将胺(D27)(350mg,1.6mmol)和3,5-二叔丁基水杨醛(960g,4.1mmol)的乙醇(40ml)溶液加热回流3h。混合物冷却,过滤,得外消旋双亚胺,625mg(63%)。
将100mg样品用手性高压液相色谱(CHIRALPAKAD,含2%乙醇的己烷洗脱)提纯,得标题化合物的单一对映体,[α]D 25=228°(C=0.13,CHCl3)。
δ(CDCl3):1.20(18H,S),1.45(18H,S),2.00(2H,m),3.25(2H,m),3.45(1H,m),3.55(1H,m),4.35(2H,m),6.95(2H,S),7.40(7H,m),8.30(2H,S)和13.15(2H,bs)。实施例1(±)3,4-双(3-叔丁基-5-甲基亚水杨基氨基)四氢呋喃氯化锰(Ⅲ)(E1)
外消旋配位体(D3)(690mg,1.53mmol)的EtOH(25ml)悬浮液与Mn(OAC)2·4H2O(750mg,3.60mmol)一起加热回流18h。加入LiCl(195mg,4.49mmol)继续回流0.5h。真空去除溶剂,残留物在硅胶(Merck 9385,100g)上用色谱法提纯,用含MeOH的CHCl3梯度洗脱,得标题化合物的棕色粉末(90mg,11%)和未反应的(D3),420mg(61%回收)。实施例2使用(E1)使2,2-二甲基-6-五氟乙基-2H-1-苯并吡喃环氧化为(±)2,2-二甲基-3,4-环氧-6-五氟乙基-2H-1-苯并吡喃(E2)
用H2O稀释次氯酸钠水溶液(16.75%W/V,4.44ml,2eg)到12.5ml,加入0.05M NaHPO4(aq)(5ml),将P H值调节至11.3。所得溶液冷却至0℃,把它加入到2,2-二甲基-6-五氟乙基-2H-1-苯并吡喃(1.39g,5mmol)和催化剂(E1)(45mg,0.1mmol,2mol%)的CH2Cl2(5ml)溶液中。混合物在0℃下搅拌1h,升温至室温再搅拌16h。
加入己烷(50ml)和水(25ml),分离有机相。用己烷(50ml)洗涤水相,收集的有机相在Mg2SO4上干燥,真空浓缩,得浅黄色油,1.42g。
高压液相色谱定量分析显示,包含有1.08g(74%)的所需环氧化物(E2),同时还有痕量(<5%回收率)的原始材料,两种化合物都与真实样品相同(1Hnmr)。实施例3(S,S)反3,4-双(3-叔丁基-5-甲基亚水杨基氨基)四氢呋喃氯化锰(Ⅲ)(E3)方法A(使用醋酸锰(Ⅱ))
使D7(0.95g,2.11mmol)和Mn(OAC)2·4H2O(1.03g,4.22mmol)的EtOH(40ml)溶液加热回流17h。加入氯化锂(268mg,6.33mmol),继续回流0.5h。冷至室温后,真空去除溶剂,在硅胶(meck 9385,梯度洗脱剂为含MeOH的CHCl3)上用色谱法提纯残留物,得棕色粉末(E3)26mg(2.3%)和未反应的(D7)883mg(72%)。方法B(使用醋酸锰(Ⅲ))5.
在CH2Cl2(17ml)和MeOH(17ml)混合物中的(D7)(1.53g,3.4mmol)溶液用Mn(OAC)3·2H2O(0.01g,3.4mmol)处理。混合物加热回流3h,冷却至室温,用氯化锂(0.21g,5.1mmol)处理。搅拌16h后,用真空减少溶剂至约8ml,加入Et2O(70ml),悬浮液搅拌1h。过滤混合物,用Et2O(3×20ml)洗涤固体,真空干燥,得(E3)棕色粉末,1.57g(86%)。
5T.Matsushita和T.Shono,Bull.Chem.Soc.Japan,1981,
54,3743-3748。实施例4使用(E3)使2,2-二甲基-6-五氟乙基-2H-1-苯并吡喃手性环氧化得到(3R,4R)-2,2-二甲基-3,4-环氧-6-五氟乙基-2H-1-苯并吡喃(E4)
用H2O稀释次氯酸钠水溶液(16.75% W/V,8.9ml 20.0mmol)到25ml。加入0.05m NaH2PO4(aq)(10ml),调节PH值至11.3。所得溶液冷却至0℃,加入到2,2-二甲基-6-五氟乙基-2H-1-苯并吡喃(2.78g,10.0mmol)和催化剂(E3)(0.108g,0.2mmol,2mol%)的二氯甲烷(10ml)溶液中。混合物在0℃下搅拌1h,升温至室温再搅拌20h。
加入己烷(100ml)和水(50ml),分离有机相。用己烷(100ml)洗涤水相,收集的有机相在Mg2SO4上干燥,真空浓缩,得浅黄色油,2.86g。
用高压液相色谱(HPLC)定量分析显示,它包含有2.09g(71%)的所需环氧化物(E4)和少量(约10%)的起始原料,两种化合物都是与真实样品相同,(1H NMR,TLC,HPLC),e.e.=66%,由手性高压液相色谱测定。实施例5制备(R,R)-5,6-双-(3,5-二叔丁基亚水杨基氨基-1,3-二噁庚环)-氧化锰(Ⅲ)
(5R,6R)-二-(3,5-二叔丁基)亚水杨基氨基-1,3-二噁庚环(1.0g,1.77mmol)(D14)和四水合醋酸锰(Ⅱ)(2.l7g,8.87mmol)悬浮在95%乙醇(50ml)中。混合物搅拌回流过夜。加入氯化锂(0.38g,8.96mmol),再继续加热30分钟。冷却反应物,加水(60ml),通过硅藻土过滤。深色沉淀用水洗净,再溶解在二氧甲烷(80ml)中,干燥(MgSO4),蒸去溶剂,得标题化合物的深棕色固体(0.9g,78%)。C35H50N2O4 MnCl计算值:C:64.36.H:7.72.N:4.29%。
实验值:C:64.57,H:7.57,N:4.09%。CI-MS:m/e565(MH-MnCl)+,235(3,5-二叔丁基水杨醛H)+。实施例6用由(R,R)-5,6-双-(3,5-二叔丁基亚水杨基氨基)-1,3-二噁庚环)氯化锰(Ⅲ)催化的次氧酸钠氧化2,2-二甲基-6-五氟乙基-2H-1-苯并吡喃制备(3S,4S)-2,2-二甲基-3,4-环氧-6-五氟乙基-2H-1-苯并吡喃
用水把次氯酸钠溶液(11.4% W/V,13.1ml,2eq)稀释至25ml,再加入0.05mol磷酸二氢钠(10ml)。用2mol含水氢氧化钠将溶液的PH值调至11.3,再加到2,2-二甲基-6-五氟乙基-2H-1-苯并吡喃(2.78g,10mmol)和(R,R)-[1,2-双-(3,5-二叔丁基甲基亚水杨基氨基)-1,3-二噁庚环]-氧化锰(Ⅲ)(0.131g,2mol%)的二氧甲烷(10ml)溶液中,并用冰浴冷却。反应混合物升温至室温,搅拌22h,这时反应基本完成。
用水(50ml)和己烷(100ml)稀释反应物,通过硅藻土过滤,分离有机相,并用另一份己烷(100ml)萃取水相。收集的有机相经干燥(MgSO4)、蒸发得标题化合物的淡黄色固体(2.6g,88%)。用HpLc测定粗产品的手性纯度为e.e=86.0%。粗产品经己烷重结晶得无色晶体m.p.72-73℃。
1Hn.m.r.(CDCl3):δ1.29(S,3H,CH3),1.59(S,3H,CH3),3.53(d,1H,H-3),3.94(d,1H,H-4),6.9(dd,1H,H-8),7.46(dd,1H,H-7),7.57(dd,1H,H-5)。
13Cn,m.r.(CDCl3):δ22.9(CH3),25.5(CH3),50.4(C-3),62.5(C-4),74.1(C-2),113.4(tq,CF3),118.4(C-8),119.1(qt,CF3),120.4(C-4′),121.1(t,C-6),128.1,128.6(2×t,C-5,7),155.7(C-8′)。EI-MS:m/e 294 M+,279(M-CH3)+。C13H11F5O2计算值:C:53.07,H:3.77%。
实验值:C:52.69,H:3.82%。实施例7(3R,4S)-双-(3,5-二叔丁基亚水杨基氨基)-四氢吡喃-氯化锰(Ⅲ)(E7)
配位体(D18)(4.81g,8.8mmol)的二氯甲烷-甲醇(1∶1,88ml)溶液用二水三醋酸锰(2.35g,8.8mmol)处理,并加热回流4h。加入氯化锂(0.56g,13.2mmol),继续加热回流1h。冷却混合物,真空浓缩,残留物用二***(220ml)研制。过滤出固体产品,用二***(2×65ml)洗涤,干燥,得(5)棕色粉末,5.3g(94%)。实施例8用(E7)使2,2-二甲基-6-五氟乙基-2H-1-苯并吡喃手性环氧化得到(3S,4S)-2,2-二甲基-3,4-环氧-6-五氟乙基-2H-1-苯并吡喃(E8)
用水稀释次氯甲钠水溶液(15.24%W/V,9.8ml,20mmol)至25ml 。加入0.05M NaH2PO4(aq)(10ml),调节PH值至11.3。所得溶液冷却至0℃,并加到2,2-二甲基-6-五氟乙基-2H-1-苯并吡喃(2.78g,10mmol)和催化剂(E7)(127mg,0.2mol%)的二氯甲烷(10ml)溶液中。混合物在0℃搅拌1h,再升温至室温继续搅拌18h。
加入已烷(100ml)和水(50ml),分离有机相。水相用己烷(100ml)洗涤,收集的有机相在MgSO4上干燥,真空浓缩,得黄色固体(2.60g)。
用hplc定量分析显示它含有2.47g(84%)所需环氧化物(E8),与真实样品相同(′Hnmr,tlc,hpLc),用手性hpLc分析ee=88.4%。实施例9(3R,4S)-双-(3-叔丁基-5-甲基亚水杨基氨基)四氢吡喃-氯化锰(Ⅲ)(E.9)
配位体(D19)(928mg,2mmol)的二氯甲烷-甲醇(1∶1,20ml)溶液用二水三醋酸锰(536mg,2mmol)处理,并加热回流3h。混合物冷却至室温,加入氯化锂(128mg,3mmol),搅拌溶液1h。真空浓缩反应混合物,残留物用二***(40ml)研制。过滤出固体产品,用二***(2×15ml)洗涤,真空干燥,得标题化合物的棕色粉未,1.0g(98%)。实施例10使用(E9)使2,2-二甲基-6-五氟乙基-2H-1-苯并吡喃手性环氧化得到(3S,4S)-2,2-二甲基-3,4-环氧-6-五氟乙基-2H-1-苯并吡喃(E8)
用水将次氧酸钠水溶涤(15.24% W/V,9.8ml,20mmol)稀释至25ml,加入0.05M NaH2PO4(aq)(10ml),调节P H至11.3。所得溶液冷至0℃,加到2,2-二甲基-6-五氨乙基-2H-1苯并吡喃(2.78g,10mmol)和催化剂(E9)(111mg,0.2mmol,2mol%)的二氯甲烷(10ml)溶液中。混合物在0℃搅拌1h,再升温至室温,继续搅拌18h。
加入已烷(100ml)和水(50ml),分离有机相。用己烷(100ml)洗涤水相,收集的有机相在MgSO4上干燥,真空浓缩,得(E8)黄色油(2.72g,93%),与真实样品相同(1Hnmr,tlc,hpLc),用手性hpLc分析ee=73%。实施例11(3R,4S)-双-(3,5-二叔丁基亚水杨基氨基)-四氢呋喃-氯化锰(Ⅲ)(E11)
使配位体(D20)(1.07g,2mmol)和二水三醋酸锰(536mg,2mmol)在二氯甲烷和甲醇(1∶1,20ml)中的溶液加热回流6.5h。溶液冷却至室温,加入氯化锂(128mg,3mmol),搅拌混合物16h。真空浓缩反应混合物,用二***(50ml)研制残留物。过滤出固体产品,用二***(2×15ml)洗涤,真空干燥,得标题化合物的棕色粉末,1.12g(89%)。实施例12用(E11)使2,2-二甲基-6-五氟乙基-2H-1-苯并吡喃手性环氧化得到(3S,4R)-2,2-二甲基-3,4-环氧-6-五氟乙基-2H-1-苯并吡喃(E4)
用水将次氯酸钠水溶液(15.24% W/V,9.8ml,20mmol)稀释至25ml,加入0.05M NaH2PO4(aq)(10ml)并调节PH至11.3。所得溶液冷却至0℃,加入到2,2-二甲基-6-五氟乙基-2H-1-苯并吡喃(2.78g,10mmol)和催化剂(E11)(124.5mg,0.2mmol,2mo1%)的二氯甲烷(10ml)溶液中。混合物在0℃搅拌1h,再升温至室温,搅拌过夜。
加入己烷(100ml)和水(50ml),分离有机相。用己烷(100ml)洗涤水相,收集的有机相经MgSO4干燥,真空浓缩,得黄色油,2.73g。
用hpLc定量分析显示它含有2.47g(84%)所需环氧化物(E4),与真实样品相同(1Hnmr,tlc,hpLc),经手性hpLc分析ee=85.6%。实施例13(3R,4S)-双-(3,5-二叔丁基亚水杨基氨基)-(2R)(三苯甲氧基甲基)四氢吡喃-氯化锰(Ⅲ)(E13)
向配位体(D24)(160mg,195μmol)的二氯甲烷-甲醇(3∶2,5ml)溶液中添加NaOH(0.93ml 0.417摩尔浓度的甲醇,390μmol)和二水三醋酸锰(52.5mg,195μmol)。溶液加热回流3h,加入氧化锂(12.5mg,300μmol),搅拌混合物搅拌15h。
真空去除溶剂,残留物用二***(10ml)研制。过滤出固体产品,用二***(2×2ml)洗涤,干燥后得标题化合物的棕色粉未,136mg(77%)。实施例14用(E13)手性环氧化2,2-二甲基-6-五氟乙基-2H-1-苯并吡喃得到(3S,4S)-2,2-二甲基-3,4-环氧-6-五氟乙基-2H-1-苯并吡喃(E8)
用水将次氯酸钠水溶液(11.4%W/V,2.6ml,4mmol)稀释至5ml,加入0.05M NaH2PO4(aq),调节PH至11.3。所得溶液冷却至0℃,并在0℃加入到2,2-二甲基-6-五氟乙基-2H-1-苯并吡喃(560mg,2mmol)和催化剂(E13)(36mg,0.04mmol)的二氯甲烷(2ml)溶液中。反应物在0℃搅拌1h,再在室温下过夜。
加入已烷(20ml)和水(10ml),分离有机相。再用已烷(20ml)萃取水相,收集的有机相经干燥MgSO4、真空去初溶剂得(E8)黄色油,(0.55g)。
hpLc定量分析显示它含有0.496g(84%)所需环氧化物(E8),与真实样品相同(1Hnmr,tlc,hpLc),经手性hpLc分析,ee=84%。实施例15(-)反-1-苯甲酰基-3,4-双-(3,5-二叔丁基亚水杨基氨基)-哌啶-氯化锰(Ⅲ)(E15)
使在二氯甲烷-甲醇(3∶2,5ml)中的(-)配位体(D28)(20mg,0.013mmol)和二水三醋酸锰(10mg,0.037mmol)的混合物加热回流4h。加入氧化锂(1.6mg,0.038mmol),继续回流1h。
真空去除溶剂,残留物在硅胶(洗脱剂:含10%甲醇的二氯甲烷)上用色谱法提纯,得标题化合物的棕色粉末,22mg(97%)。实施例16用(E15)手性环氧化2,2-二甲基-6-五氟乙基-2H-1-苯并吡喃得到(3S,4R)-2,2-二甲基-3,4-环氧-5-五氟乙基-2H-1-苯并吡喃(E4)
2,2-二甲基-6-五氟乙基-2H-1-苯并吡喃(560mg,2mmol)和催化剂(E15)(22mg,0.03mmol)的二氯甲烷(2ml)溶液冷至0℃。加入次氯酸钠水溶液(11.4%W/V,2.6ml,4mmol)和0.05M NaH2PO4(aq)(2mL,PH调至11.3)的混合物。混合物在0℃搅拌1h,升温至室温再搅拌过夜。
混合物用水(10ml)稀释,用己烷(4×20ml)萃取。收集的有机相用水(10ml)洗涤,在NaSO4上干燥,蒸发,得所需环氧化物,492mg(83%)。手性hplc分析显示ee=77%。
Claims (12)
2.根据权利要求1的化合物,其中M是Mn。
3.根据权利要求2的化合物,其中Mn处于氧化状态(Ⅱ)或(Ⅲ)。
4.根据权利要求1的化合物,其中A是氯。
5.根据权利要求1-4中任一权项的化合物,其中s和t是零,r是1,Ra是氢,B是氧,E是CH2;或r、s和t是1,Ra、Rb和Rc是氢,B和E都是氧;或s是零,r和t都是1,Ra是氢或三苯甲氧基亚甲基,Rc是氢,B是氧,E是-CH2-;或者r和t都是1,s是零,Ra和Rc是氢,B是NRd,其中Rd是苯羰基,E是CH2。
6.根据权利要求1-5中任一权项的化合物,其中R1和R8是叔丁基,R3和R6是叔丁基或甲基,R2、R4、R5和R7是氢。
7.一种化合物,它选自:
(±)3,4-双-(3-叔丁基-5-甲基亚水杨基氨基)四氢呋喃氯化锰(Ⅲ);
(S,S)反3,4-双-(3-叔丁基-5-甲基亚水杨基氨基)四氢呋喃氯化锰(Ⅲ);
(R,R)-5,6-双-(3,5-二叔丁基亚水杨基氨基)-1,3-二噁庚环-氯化锰(Ⅲ);
(3R,4S)-双-(3,5-二叔丁基亚水杨基氨基)-四氢吡喃-氯化锰(Ⅲ);
(3R,4S)-双-(3-叔丁基-5-甲基亚水杨基氨基)-四氢吡喃-氯化锰(Ⅲ);
(3S,4S)-双-(3,5-二叔丁基亚水杨基氨基)-四氢呋喃-氯化锰(Ⅲ);
(3R,4S)-双-(3,5-二叔丁基亚水杨基氨基)-(2R)-(三苯甲氧基甲基)四氢吡喃-氯化锰(Ⅲ);
(-)反-1-苯甲酰基-3,4-双-(3,5-二叔丁基亚水杨基氨基)哌啶-氯化锰(Ⅲ)。
8.一种在有氧源和根据权利要求1所定义的通式(Ⅰ)的手性催化剂存在时对映选择地环氧化前手性烯烃的方法。
9.根据权利要求8的方法,其中前手性烯烃包含下组中的一个基团作为其部分结构:环己烯、5,6-二氢-2H-吡喃、1,2,5,6-四氢吡啶、1,2,3,4-四氢吡啶和5,6-二氢-2H-噻喃。
10.根据权利要求8或9的方法,其中前手性烯烃包含作为其部分结构的下组中的一个基团:1,2-二氢萘、2H-苯并吡喃、1,2-二氢喹啉、1,2-二氢异喹啉和2H-1,2-苯并硫吡喃。
11.根据权利要求8-10中任一权项的方法,其中前手性烯烃是2,2二甲基-6-五氟乙基-2H-1-苯并吡喃。
12.根据权利要求11的方法,其中2,2-二甲基-6-五氟乙基-苯并吡喃(3S,4S)-环氧化物产品进一步转化为反-6-五氟乙基-3,4-二氢-2,2-二甲基-4R-(哌啶-2-酮-1-基)-2H-1-苯并吡喃-3S-醇。
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EP0813447B1 (en) * | 1995-03-08 | 1998-10-21 | Shell Internationale Researchmaatschappij B.V. | Bridged bis-amido group 4 metal compounds in a catalyst composition |
US6713045B1 (en) | 1995-06-02 | 2004-03-30 | Research Corporation Technologies, Inc. | Targeted magnetic resonance imaging agents for the detection of physiological processes |
ATE295408T1 (de) | 1997-03-07 | 2005-05-15 | Procter & Gamble | Bleichmittelzusammensetzungen |
ZA981883B (en) * | 1997-03-07 | 1998-09-01 | Univ Kansas | Catalysts and methods for catalytic oxidation |
US20030017941A1 (en) | 1997-03-07 | 2003-01-23 | The Procter & Gamble Company | Catalysts and methods for catalytic oxidation |
TWI246520B (en) | 1997-04-25 | 2006-01-01 | Mitsui Chemicals Inc | Processes for olefin polymerization |
US5981424A (en) * | 1997-07-31 | 1999-11-09 | Sunoco, Inc. (R&M) | Catalysts for hydroxylation and ammination of aromatics using molecular oxygen as the terminal oxidant without coreductant |
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US6656450B2 (en) | 2000-07-17 | 2003-12-02 | California Institute Of Technology, Inc. | Macrocyclic magnetic resonance imaging contrast agents |
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Title |
---|
J.AM.CHEM.SOC 1986,108,2309-2320 1986.1.1 EPOLDATION of olefis witllt catioic(sale) Mn complex * |
J.AM.CHEM.SOC 1986,108,2309-2320 1986.1.1 EPOLDATION of olefis witllt catioic(sale) Mn complex;J.AM.CHEM.SOC 1990,112,2801-2803 1990.3.1 W.Zang Enanllcosedtive epoxydation of uivfuction * |
J.AM.CHEM.SOC 1990,112,2801-2803 1990.3.1 W.Zang Enanllcosedtive epoxydation of uivfuction * |
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