Asymmetric Syn-Selective Henry Reaction Catalyzed by the
Sulfonyldiamine-CuCl-Pyridine System
Takayoshi Arai,*Ryuta Takashita,Yoko Endo,Masahiko Watanabe,and Akira Yanagisawa Department of Chemistry,Graduate School of Science,Chiba Uni V ersity,Inage,Chiba263-8522,Japan
tarai@faculty.chiba-u.jp
Recei V ed February20,2008
A catalytic asymmetric Henry reaction has been developed with u of a sulfonyldiamine-CuCl complex as a catalyst.A ries of new binaphthyl-containing sulfonyldiamine ligands(2a-h)were readily synthesized in two steps starting from commercially available chiral1,2-diamines.The(R,R)-diamine-(R)-binaphthyl ligand(2d)-CuCl complex smoothly catalyzed the enantiolective Henry reaction with the assistance of pyridine to give the corresponding adduct with high enantiomeric excess(up to93%). Moreover,the2d-CuCl-pyridine system promotes the diastereolective Henry reaction in syn-lective manner to give the adduct in up to99%yield with92:8syn/anti lectivity.The enantiomeric excess of the syn-adduct was84%ee.
Introduction手起皮是什么原因
The Henry(nitroaldol)reaction is a powerful and atom-economical carbon-carbon bond-forming reaction that can be ud to create a new stereogenic center at the -position of a nitro functionality.1Becau the resulting -nitro alcohol adducts can be transformed to various biologically important building blocks such as -amino alcohols and R-hydroxy ketones,recent rearch has focud on the catalytic asymmetric version of the Henry reaction.2Since the original pioneering work on hetero-bimetallic multifunctional catalysts containing lanthanoid ele-ments,3various types of chiral metal catalysts(containing metals such as Zn,4Co,5Cu,6Mg,7and Cr8)and organocatalysts9have been developed.Among the,a Cu-bad asymmetric catalyst, examined at room temperature,is particularly promising due to its high catalytic activity and excellent enantiolectivity. Following on from the ground-breaking work of Jørgenn and Evans,6a,b we succeeded in developing a C2-symmetric diamine (1)-CuCl-catalyzed Henry reaction.10However,little rearch has been carried out into Cu-catalyzed diastereolective Henry reactions.11We report herein the development of a syn-lective asymmetric Henry reaction using newly developed sulfonyl-
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10.1021/jo800412x CCC:$40.75 2008American Chemical Society J.Org.Chem.2008,73,4903–49064903 Published on Web05/31/2008
diamine (2)-CuCl catalysts.12Remarkable acceleration effects due to pyridine are also prented.Results and Discussion
As propod by Evans et al.,the Lewis acidity of the Cu atom is important for activating the aldehyde.6b This realization led us to design a new asymmetric ligand in which one of the nitrogen atoms of the 1,2-diamine group was sulfonylated to increa the acidity of the metal complex (Figure 1).
The binaphthyl-containing sulfonyldiamines were readily synthesized in two steps starting from commercially available 1,2-diamines.13Sulfonylation of the appropriate 1,2-diamine,followed by alkylation with chiral 2,2′-dibromomethyl-1,1′-binaphthalene,provided a ries of new sulfonyldiamine ligands,as shown in Scheme 1.(See details in the Experimental Section.)Before examining the diastereolective Henry reaction,the potential of the newly developed sulfonyldiamine ligands 2was examined in an enantiolective reaction by using o -nitroben-zaldehyde (3a ),which have been utilized as a test substrate.10However,it was soon revealed that the reaction of 3a with nitromethane was not smoothly promoted by 2-CuCl.When
we examined straightforward analogues of 1(2a or 2b ),containing an (R ,R )-diamine group and an (
S )-binaphthyl skeleton,the reaction with 2a provided only trace amounts of the adduct (rt,45h);2b -CuCl gave the adduct in 22%yield with only 1%ee (rt,40h).However,the u of the (R ,R )-diamine-(R )-binaphthyl ligand 2d ,an epimer of 2b ,unexpectedly gave the (R )-enriched product in 68%yield with 31%ee (rt,23h);2c -CuCl gave only trace amounts of the adduct.
Becau the Henry reaction is thought to employ basicity to generate the nitronate,the effects of various basic additives in promoting the reaction were examined.
As expected,the addition of basic amines enhanced the 2d -catalyzed Henry reaction,although the enantiomeric excess were diminished (entries 2-6,Table 1).Surprisingly,the addition of pyridine,a weak ba,improved the chemical yield while increasing the enantiomeric excess to 57%(entry 7).When the amount of pyridine was incread to 25equiv to ligand,the adduct was obtained in 97%yield with 67%ee (entry 9);the u of 30equiv of pyridine resulted in a reduction in enanti-olectivity to 55%ee (entry 10).The remarkable acceleration effects with improvement of enantiolectivity were also examined in the Henry reaction by using the other sulfonyl-diamine ligands (2);the results are summarized in Table 2.The u of the cyclohexyldiamine analogue 2c gave the adduct almost racemically (entry 3,Table 2).Ligand 2b ,the diastere-omer of 2d ,was also unsuitable for the enantiolective Henry reaction (entry 2).
(6)(a)Christenn,C.;Juhl,K.;Jørgenn,K.A.Chem.Commun.2001,2222–2223.(b)Evans,D.A.;Seidel,D.;Rueping,M.;Lam,H.W.;Shaw,J.T.;Downey,C.W.J.Am.Chem.Soc.2003,125,12692–12693.(c)Gan,C.;Lai,G.;Zhang,Z.;Wang,Z.;Zhou,M.-M.Tetrahedron:Asymmetry 2006,17,725–728.(d)Maheswaran,H.;Prasanth,K.L.;Krishna,G.G.;Ravikumar,K.;Sridhar,B.;Kantam,M.L.Chem.Commun.2006,4066–4068.(e)Ma,K.;You,J.Chem.Eur.J.2007,13,1863–1871.(f)Bandini,M.;Piccinelli,F.;Tommasi,S.;Umani-Ronchi,A.;Ventrici,C.Chem.Commun.2007,616–618.(g)Qin,B.;Xiao,X.;Liu,X.;Huang,J.;Wen,Y.;Feng,X.J.Org.Chem.2007,72,9323–9328.(h)Bandini,M.;Benaglia,M.;Sinisi,R.;Tommasi,S.;Umani-Ronchi,A.Org.Lett.2007,9,2151–2153.(i)Xiong,Y.;Wang,F.;Huang,X.;Wen,Y.;Feng,X.Chem.Eur.J.2007,13,829–833.(j)Colak,M.;Aral,T.;Hosgo ¨ren,H.;Demirel,N.Tetrahedron:Asymmetry 2007,18,1129–1133.(k)Jiang,J.-J.;Shi,M.Tetrahedron:Asymmetry 2007,18,1376–1382.(l)Blay,G.;Climent,E.;Fera ´ndez,I.;Herna ´ndaz-Olmos,V.;Pedro,J.R.Tetrahedron:Asymmetry 2007,18,1603–1612.(m)Arai,T.;Yokoyama,N.;Yanagisawa,A.Chem.Eur.J.2008,14,2052–2059.
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性感的美女图片(8)Kowalczyk,R.;Sidorowicz,L.;Skarzewski,J.Tetrahedron:Asymmetry 2007,18,2581–2586.
(9)(a)Corey,E.J.;Zhang,F.-Y.Angew.Chem.,Int.Ed.1999,38,1931–1934.(b)Ooi,T.;Doda,K.;Maruoka,K.J.Am.Chem.Soc.2003,125,2054–2055.(c)Marcelli,T.;van der Haas,R.N.S.;van Maarveen,J.H.;Hiemstra,H.Angew.Chem.,Int.Ed.2006,45,929–931.(d)Sohtome,Y.;Hashimoto,Y.;Nagasawa,K.Eur.J.Org.Chem.2006,2894–2897.(e)Mandal,T.;Samanta,S.;Zhao,C.-G.Org.Lett.2007,9,943–945.(f)Uraguchi,D.;Sakaki,S.;Ooi,T.J.Am.Chem.Soc.2007,129,12392–12393.
(10)Arai,T.;Watanabe,M.;Fujiwara,A.;Yokoyama,N.;Yanagisawa,A.Angew.Chem.,Int.Ed.2006,45,5978–5981.
(11)A study on Cu-catalyzed anti -lective Henry reaction:Risgaard,T.;Gothelf,K.V.;Jørgenn,K.A.Org.Biomol.Chem 2003,1,153–156.(12)Though we recently report a diastereolective Henry reaction using newly developed diamine -Cu(OAc)2catalyst,it was 80:20syn /anti lectivity:Arai,T.;Watanabe,M.;Yanagisawa,A.Org.Lett.2007,9,3595–3597.
(13)Reprentative reports on chiral sulfonyl-1,2-diamines in asymmetric catalysis:(a)Hashiguchi,S.;Fujii,A.;Takehara,J.;Ikariya,T.;Noyori,R.J.Am.Chem.Soc.1995,117,7562–7563.(b)W
atanabe,M.;Murata,K.;Ikariya,T.J.Am.Chem.Soc.2003,125,7508–7509.(c)Hayes,A.M.;Morris,D.J.;Clarkson,G.J.;Wills,M.J.Am.Chem.Soc.2005,127,7318–7319
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F IGURE 1.Sulfonyldiamine ligands.
对账函模板S CHEME 1.
Synthesis of Sulfonyldiamine Ligands
(2)
T ABLE 1.
Effects of Basic Additives on the 2d -CuCl-Catalyzed
Enantiolective Henry
Reaction
姚起云
无私奉献作文entry ba amount of ba a
time (h)yield (%)ee (%)12368312DBU 12196<13DIPEA 12192274Et 3N
123841552,6-lutidine 102390316DMAP 501784<17Py 101883578Py 201685639Py 2518976710
Py
30
16
94
55
a
Equivalent bad on ligand.
Arai et al.
4904J.Org.Chem.Vol.73,No.13,2008
Regarding the efficient reaction sphere of 2d produced by the combination of (R ,R )-diphenylethylenediamine and (R )-binaphthyl moiety,an analogue of tosyl-(R ,R )-diphenyl-ethylenediamine -biphenyl ligand (2i )was prepared,and applied to the enantiolective Henry reactio
n of 3a .Under similar conditions with 25equiv of py to 2i ,the reaction was smoothly catalyzed to give the adduct in 73%yield with 46%ee,which is superior to the results with 2b (86%yield,3%ee in entry 2,Table 2).This suggests the 2i -CuCl-catalyzed reaction would have a similar transition state to that of 2d -CuCl catalysis,and the appropriate transition state of 2d -CuCl catalysis would be more stable than that of 2b -CuCl.The formation of the 2d -CuCl complex was strongly suggested by ESI mass spectrometry by the obrvation of an ion peak [2d +CuCl +H]+at m /z 742.
The nature of the R 2group substituted at the sulfonyl group had a strong effect on the asymmetric induction ability,and the 2d -CuCl -pyridine system gave the best overall result,with high chemical yield and enantiomeric excess.The scope and limitations of the 2d -CuCl -pyridine catalyst system were examined,and the results are summarized in Table 3.
Various aldehydes were smoothly converted to Henry adducts at room temperature,and in all cas,the (R )-enriched products were obtained by using the tosyl-(R ,R )-diphenylethylenedi-amine -(R )-binaphthyl ligand 2d .The simplest aromatic alde-hyde,benzaldehyde (3c ),was converted to the Henry adduct in 94%yield with 83%ee.Typically,the u of aliphatic aldehydes provided the corresponding adducts with higher enantiolec-tivities than tho obtained with aromatic aldehydes.In par-ticular,R -branched aliphatic aldehydes such as pivalaldehyde (3k )and cyclohexan
ecarboxaldehyde (3l )gave the adducts with excellent enantiolectivity s up to 93%ee s without a significant decrea in reaction rate.Although the role of pyridine is unclear at prent,its effect in accelerating the Henry reaction would suggest that it enforces nucleophilic addition of nitronate to the Cu Lewis acid-activated aldehyde in a cooperative manner.3b
Finally,the optimized catalyst system was applied to the diastereolective Henry reaction;the results are shown in Table 4.
Although the reaction with nitroethane was slow,the reaction of 3f without the u of ethanol as a solvent provided the adduct with moderate syn -lectivity.This syn -lectivity was in contrast with the results of Jørgenn’s bis(oxazoline)-Cu(OTf)2-catalyzed anti -lective Henry reaction with silyl nitronate.11Diastereolectivity was also dramatically improved
when R -branched aliphatic aldehydes were ud;for example,the reaction of 3l with nitroethane gave the product in 99%yield with 92:8syn /anti lectivity.The enantiomeric excess of the syn -adduct was 84%(entry 4).14
To explain the syn -lectivity of the reaction,a plausible transition state is shown in Scheme 2.The formation of this Cu-containing cyclic transition state species would result in syn -lectivity due to st
eric hindrance.15In the Newman projections,the structure S1,which leads to the syn -adduct,is the most favorable.
(14)2i -CuCl-catalyzed diastereolective Henry reaction of 3l with nitro-ethane gave the adduct in 58%yield with 82:18syn /anti lectivity.The enantiomeric excess of the syn -adduct was 60%.
(15)Sasai,H.;Tokunaga,T.;Watanabe,S.;Suzuki,T.;Itoh,N.;Shibasaki,M.J.Org.Chem.1995,60,7388–7389.
T ABLE 2.
Enantiolective Henry Reaction Catalyzed by
2-CuCl -
Pyridine
entry sulfonyldiamine
time (h)Yield (%)
ee (%)12a 4053<122b 1686332c 4098142d 18976752e 23862762f 1792<172g 20993582h 2090639
2i
27
73
46
a
25equiv of py to ligand.
T ABLE 3.
2d -CuCl-Catalyzed Enantiolective Henry
Reaction
entry aldehyde time (h)yield (%)ee (%)13a 18976723b 23897033c 23948343d 18946053e 15995963f 22728373g 18968783h 17978093i 189585103j 219892113k 20799312
3l
16
90
93
a
25equiv of py to ligand.
T ABLE 4.
2d -CuCl-Catalyzed Diastereolective Henry Reaction
a
entry aldehyde R ′time (h)yield (%)syn /anti ee [%]syn /anti
学习不好怎么办
13f Me 165580/2066/2223i Me 437073/2764/2733j Me 948985/1582/3043l Me 419992/884/4353l Et 426391/981/5563m Me 669076/2480/2273m Et 969274/2668/238
3n
Me
14
81
90/10
81/32
a
25equiv of py to ligand.
Asymmetric Syn-Selecti V e Henry Reaction
J.Org.Chem.Vol.73,No.13,20084905
Conclusion
In conclusion,we have succeeded in developing a new chiral sulfonyldiamine ligand as part of a catalyst system for diastereo-and enantiolective Henry reactions.With the assistance of pyridine,the reactions proceeded smoothly to provide the corresponding adducts with high syn -lec
tivity and high enantiomeric excess.Further detailed elucidation of the reaction mechanism is currently in progress.Experimental Section
Preparation of (1R ,2R )-N -(R )-Binaphtyl-N ′-tosyl-1,2-diphe-nylethanediamine (2d).A solution of (1R ,2R )-1,2-diphenyl-ethanediamine (212mg,1.0mmol),p -toluenesulfonyl chloride (191mg,1.0mmol),and triethylamine (154µl,1.1mmol)in dichlo-romethane (5.0mL)was stirred at room temperature for 28h under Ar.The reaction was quenched by the addition of distilled water,and the aqueous layer was extracted with dichloromethane.The organic pha was washed with brine,and then dried over sodium sulfate.After removal of the solvent under reduced pressure,the residue was purified by column chromatography (using neutral silica gel,n -hexane/ethyl acetate )1:1)to give (1R ,2R )-N -tosyl-1,2-diphenylethanediamine (265mg,72%yield,as a white solid).A solution of (1R ,2R )-N -tosyl-1,2-diphenylethanediamine (160mg,0.437mmol),(R )-2,2′-dibromomethyl-1,1′-binaphthalene (211mg,0.481mmol),and triethylamine (134µL,0.960mmol)in dichloromethane (2.2mL)was stirred at room temperature.After being stirred for 67h under Ar,the reaction was quenched by the addition of distilled water,and the aqueous layer was extracted with dichloromethane.The organic pha was washed with brine,and dried over sodium sulfate.After removal of the solvent under reduced pressure,the residue was purified by column chromatog-raphy (using neutral silica gel,n -hexane/ethyl acetate )5:1)to give 2d (280mg,99%yield,as a pale yellow solid).
Spectral data for 2d:.[R ]20D +28.6(c 0.95,CHCl 3).IR (ATR)3263,3035,2339,1508,1456,1317,1157,1066,928,812,752,696,667cm -1.1H NMR (400MHz,CDCl 3)δ2.29(s,3H),3.58(d,J )12.1Hz,2H),3.85(d,J )12.3Hz,2H),3.96(d,J )10.6Hz,1H),4.92(d,J )10.6Hz,1H),6.80-7.03(m,12H),7.16-7.22
(m,2H),7.31-7.43(m,8H),7.73(d,J )8.5Hz,2H),7.84(d,J )8.2Hz,2H).13C NMR (100MHz,CDCl 3)δ21.3,52.1,58.4,74.9,125.3,125.5,126.8,126.9,127.2,127.3,127.48,127.53,127.6,127.7,127.8,128.0,128.15,128.20,128.4,128.8,129.2,130.9,132.8,133.2,134.6,135.4,137.7,137.8,142.6.HRMS (FAB +)calcd for C 43H 37N 2O 2S (M ++H)645.2576,found 645.2527.
General Procedure of the 2d -CuCl-Catalyzed Enantiolec-tive Henry Reaction.The catalyst was prepared by a complex formation of ligand 2d (12.9mg,0.02mmol)with CuCl (1.8mg,0.018mmol)in anhydrous dichloromethane (1.0mL)under Ar.After the solution was stirred overnight at room temperature,solvent was removed under reduced pressure.Then,the residue was dissolved in EtOH (0.72mL).To the resulting clear green solution were added nitromethane (196µL,3.64mmol),pyridine (40µL,0.5mmol),and cyclohexanecarboxaldehyde (44µL,0.364mmol)under Ar.After the reaction was stirred for 16h at room temperature,the volatile components were removed under reduced pressure and the residue was purified by column chromatography (using neutral silica gel,n -hexane/ethyl acetate )4:1)to afford the adduct (56.6mg,90%yield).The enantiomeric excess was determined by H
PLC analysis.
2d -CuCl-Catalyzed Diastereolective Henry Reaction (En-try 4,Table 4).The catalyst was prepared by a complex formation of ligand 2d (12.9mg,0.02mmol)with CuCl (1.8mg,0.018mmol)in anhydrous dichloromethane (1.0mL)under Ar.After the reaction was stirred an overnight at room temperature,solvent was removed under reduced pressure.To the residue were added nitroethane (261µL,3.64mmol),pyridine (40µL,0.5mmol),and cyclohexanecar-boxaldehyde (44µL,0.364mmol)under Ar.After the reaction was stirred for 41h at room temperature,the volatile components were removed under reduced pressure and the residue was purified by column chromatography (using neutral silica gel,n -hexane/ethyl acetate )6:1)to afford the adduct (67.8mg,99%yield).Diastereolectivity was determined by 1H NMR spectroscopy and the enantiomeric excess was determined by HPLC analysis.
Acknowledgment.This work was supported by the Industrial Technology Rearch Grant Program (2006)from the New Energy and Industrial Technology Development Organization (NEDO)of Japan,a Grant-in Aid for Scientific Rearch from the Ministry of Education,Culture,Sports,Science.We thank Prof.K.Nagasawa at the Tokyo University of Agriculture and Technology for providing the analytical data for the diastereo-lective Henry reactions.We thank Mr.Y.Taneda and Ms.K.Suzuki for technica
l support.
Supporting Information Available:HPLC conditions for analyzing Henry adducts and copies of 1H and 13C NMR spectra for all new compounds.This material is available free of charge via the Internet at
JO800412X
S CHEME 2.Plausible Transition Structure for the Syn -Selective Henry
Reaction
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4906J.Org.Chem.Vol.73,No.13,2008情感吧
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