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1.
Kumagai N Matsunaga S Kinoshita T Harada S Okada S Sakamoto S Yamaguchi K Shibasaki M 《Journal of the American Chemical Society》2003,125(8):2169-2178
Full details of our newly developed catalyses with asymmetric zinc complexes as mimics of class II zinc-containing aldolase are described. A Et(2)Zn/(S,S)-linked-BINOL complex was developed and successfully applied to direct catalytic asymmetric aldol reactions of hydroxyketones. A Et(2)Zn/(S,S)-linked-BINOL 1 = 2/1 system was initially developed, which efficiently promoted the direct aldol reaction of 2-hydroxy-2'-methoxyacetophenone (7d). Using 1 mol % of (S,S)-linked-BINOL 1 and 2 mol % of Et(2)Zn, we obtained 1,2-dihydroxyketones syn-selectively in high yield (up to 95%), good diastereomeric ratio (up to 97/3), and excellent enantiomeric excess (up to 99%). Mechanistic investigation of Et(2)Zn/(S,S)-linked-BINOL 1, including X-ray analysis, NMR analysis, cold spray ionization mass spectrometry (CSI-MS) analysis, and kinetic studies, provided new insight into the active oligomeric Zn/(S,S)-linked-BINOL 1/ketone 7d active species. On the basis of mechanistic investigations, a modified second generation Et(2)Zn/(S,S)-linked-BINOL 1 = 4/1 with molecular sieves 3A (MS 3A) system was developed as a much more effective catalyst system for the direct aldol reaction. As little as 0.1 mol % of (S,S)-linked-BINOL 1 and 0.4 mol % of Et(2)Zn promoted the direct aldol reaction smoothly, using only 1.1 equiv of 7d as a donor (substrate/ligand = 1000). This is the most efficient, in terms of catalyst loading, asymmetric catalyst for the direct catalytic asymmetric aldol reaction. Moreover, the Et(2)Zn/(S,S)-linked-BINOL 1 = 4/1 system was effective in the direct catalytic asymmetric aldol reaction of 2-hydroxy-2'-methoxypropiophenone (12), which afforded a chiral tetrasubstituted carbon center (tert-alcohol) in good yield (up to 97%) and ee (up to 97%), albeit in modest syn-selectivity. Newly developed (S,S)-sulfur-linked-BINOL 2 was also effective in the direct aldol reaction of 12. The Et(2)Zn/(S,S)-sulfur-linked-BINOL 2 = 4/1 system gave aldol adducts anti-selectively in good ee (up to 93%). Transformations of the aldol adducts into synthetically versatile intermediates were also described. 相似文献
2.
以N-苄氧羰基-(S)-脯氨酸和5-(1-氨基烷基)四氮唑(烷基: 甲基、乙基、2-苯基乙基)为原料, 经两步反应合成了3个新颖的有机催化剂: (S)-5-脯氨酰胺基甲基四氮唑(3a), (S,S)-5-(1-脯氨酰胺基乙基)四氮唑(3b)和(S,S)-5-(1-脯氨酰胺 基-2-苯基乙基)四氮唑(3c), 并首次将其用于催化丙酮和含吸电子基芳香醛的不对称直接aldol反应. 在室温条件下, 催化剂3b表现出较好的催化活性, 产物的ee值最高可达96%. 相似文献
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[reaction: see text] A simple and efficient method for the synthesis of highly enantiomerically enriched beta-hydroxy-alpha-amino acid derivatives has been developed. Direct asymmetric aldol reactions of a glycine aldehyde (aminoacetaldehyde) derivative have been performed under organocatalysis using l-proline or (S)-5-pyrrolidine-2-yl-1H-tetrazole. The reactions afforded anti-beta-hydroxy-alpha-amino aldehydes in good yield with high diastereoselectivity (dr up to >100:1) and high enantioselectivity (up to >99.5% ee), which were easily transformed into beta-hydroxy-alpha-amino acid derivatives. 相似文献
5.
The organocatalytic asymmetric direct aldol reaction of trifluoroacetaldehyde ethyl hemiacetal with aromatic methyl ketones in the presence of a catalytic amount of (S)-5-(pyrrolidin-2-yl)-1H-tetrazole in dichloroethane at 40 °C proceeds smoothly to produce (R)-4,4,4-trifluoro-1-aryl-3-hydroxy-1-butanones in high yields with up to 90% ee. 相似文献
6.
[reaction: see text] (-)-(6S,7S,8S,9R,10S,2'S)-Membrenone-A and (-)-(6S,7S,8S,9R,10S)-membrenone-B were prepared in 11 steps (3% and 2.4% overall yield, respectively). Key steps included a tin(II)-mediated aldol followed by a syn selective reduction, giving the C7-C9 stereocenters, a second chain extending aldol coupling, and a p-TsOH-promoted cyclization/dehydration giving the common gamma-dihydropyrone precursor. We have thus established that synthetic (-)-(6S,7S,8S,9R,10S,2'S)-membrenone-A, (-)-(6S,7S,8S,9R,10S)-membrenone-B, and (-)-(6S,7S,8S,9R,10S)-membrenone-C are the enantiomers of the natural products. 相似文献
7.
The synthesis of serricornin [(4S,6S,7S)-7-hydroxy-4,6-dimethylnonan-3-one], a sex pheromone produced by the female cigarette beetle (Lasioderma serricorne F.), in seven steps from readily available racemic 1,4-dioxa-8-thiaspiro[4.5]decane-6-carboxaldehyde (6) is described. The key steps include enantioselective aldol reaction of 6 with tetrahydrothiopyran-4-one catalyzed by 5-[(2S)-pyrrolidine-2-yl]-1H-tetrazole to fabricate the tetrapropionate skeleton, stereoselective Li(s)Bu(3)BH reduction of the resulting aldol adduct, Barton-McCombie deoxygenation, and Raney nickel desulfurization. 相似文献
8.
[reaction: see text] The total synthesis of (2S,3S)-2,3-dihydro-6-[(1'S, 2'R)-2-hydroxy-1-methylbutyl]-3,5-dimethyl-2-[(1'S)-1-methylpropyl]-4H-pyran-4-one (3), the (-)enantiomer of the marine polypropionate, maurenone, was achieved in nine linear steps (13% overall yield) from (R)-2-benzylpentan-3-one ((R)-14) and (R)-2-benzoyloxypentan-3-one ((R)-15). Key fragments were synthesized using highly diastereoselective syn and anti boron aldol reactions and were coupled using a lithium-mediated aldol reaction. Trifluoroacetic acid-promoted cyclization/dehydration was then used to install the gamma-dihydropyrone ring. Eight isomers of one enantiomeric series were synthesized by coupling two ketones with each of four aldehydes. Comparison of the 13C NMR data for the eight isomers with that reported for maurenone established the relative stereochemistry of the natural product. 相似文献
9.
[structure: see text]. 1,1'-Binaphthyl-2,2'-diamine-based (S)-prolinamides in the presence of stearic acid were able to promote the direct aldol condensation of cyclohexanone and other ketones with different aldehydes in the presence of a massive amount of water in very good yields, high diastereoselectivity, and up to 99% ee. The behavior of both C2- and C1-symmetric catalysts in combination with different additives was investigated, and a preliminary experiment of recovering and recycling of the catalytic system was also attempted. 相似文献
10.
The aldol reaction of acetone with aldehydes in aqueous medium under catalysis by zinc-proline (Zn(L-Pro)2) and secondary amines such as proline, (2S,4R)-4-hydroxyproline (Hyp) and (S)-(+)-1-(2-pyrrolidinomethyl)pyrrolidine (PMP) is shown to proceed by an enamine mechanism, as evidenced by reductive trapping of the iminium intermediate, while the aldol reaction of dihydroxyacetone (DHA) under catalysis by zinc-proline and by general bases such as N-methylmorpholine (NMM) is shown to occur under rate-limiting deprotonation of the alpha-carbon and formation of an enolate intermediate. 相似文献
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[reaction: see text] Asymmetric aldol addition reactions have been conducted with (1R,2S)-ephedrine-derived 3,4,5,6-tetrahydro-2H-1,3,4-oxadiazin-2-one (2). Diastereoselectivities range from 75:25 to 99:1 for the formation of the crude non-Evans syn adducts 8a-h. The facial selectivity of the enolate is directed by the stereogenic N(4)-methyl substituent. Aldol adduct 8a is readily cleaved by acid hydrolysis to afford (2S,3S)-3-hydroxy-2-methyl-3-phenylpropionic acid (9) in >95% ee. 相似文献
13.
Garrabou X Calveras J Joglar J Parella T Bujons J Clapés P 《Organic & biomolecular chemistry》2011,9(24):8430-8436
Aldol addition reactions of dihydroxyacetone (DHA) to N-Cbz-amino aldehydes catalyzed by L-rhamnulose-1-phosphate aldolase (RhuA) in the presence of borate buffer are reported. High yields of aldol adduct (e.g. 70-90%) were achieved with excellent (>98?:?2 syn/anti) stereoselectivity for most S or R configured acceptors, which compares favorably to the reactions performed with DHAP. The stereochemical outcome was different and depended on the N-Cbz-amino aldehyde enantiomer: the S acceptors gave the syn (3R,4S) aldol adduct whereas the R ones gave the anti (3R,4R) diastereomer. Moreover, the tactical use of Cbz protecting group allows simple and efficient elimination of borate and excess of DHA by reverse phase column chromatography or even by simple extraction. This, in addition to the use of unphosphorylated donor nucleophile, makes a useful and expedient methodology for the synthesis of structurally diverse iminocyclitols. The performance of aldol additions of dihydroxyacetone phosphate (DHAP) to N-Cbz-amino aldehydes using RhuA and L-fuculose-1-phosphate aldolase (FucA) catalyst in borate buffer was also evaluated. For FucA catalysts, including FucA F131A, the initial velocity of the aldol addition reactions using DHAP were between 2 and 10 times faster and the yields between 1.5 and 4 times higher than those in triethanolamine buffer. In this case, the retroaldol velocities measured for some aldol adducts were lower than those without borate buffer indicating some trapping effect that could explain the improvement of yields. 相似文献
14.
[reaction: see text] A concise and enantioselective synthesis of (S)-2-cyclohexyl-2-phenylglycolic acid as a key intermediate for (S)-oxybutynin is reported. The crucial asymmetric tetrasubstituted carbon center was constructed with excellent stereoselectivity through the proline-catalyzed direct asymmetric aldol reaction between cyclohexanone and ethyl phenylglyoxylate under mild conditions. 相似文献
15.
WANG Rui WEI Zhonglin GUO Jing FENG Yusha XU Enjie DUAN Haifeng LIN Yingjie YANG Qingbiao DU Jianshi LI Yaoxian 《高等学校化学研究》2018,34(2):180-185
Chiral organocatalysts of 4-adamantane amide based on L-proline with double hydrogen potential were synthesized and used in asymmetric aldol reactions. The reactions were evaluated in toluene under -20℃. A series of aldol products was obtained from moderate to good yields(up to 98%) with excellent diastereoselectivities(up to >99:1) and enantioselectivities(up to >99%). The aldol products in the system were separated by α-cyclodextrin via host-guest interaction and determined by chiral HPLC. The catalyst could be reused up to five times. The 4-substitution position played an important role in diastereoselectivity and enantioselectivity. 相似文献
16.
Rodríguez-Cisterna V Villar C Romea P Urpí F 《The Journal of organic chemistry》2007,72(17):6631-6633
Stereoselectivity of TiCl4-mediated aldol reactions from (S)-2-benzyloxy-3-pentanone is dramatically improved when the reaction is carried out in the presence of 1.1 equiv of tetrahydrofuran (THF) or 1,2-dimethoxyethane (DME). The resultant 2,4-syn-4,5-syn adducts are then obtained in diastereomeric ratios up to 97:3, which proves that the appropriate choice of the Lewis acid (TiCl4-THF or DME vs Ti(i-PrO)Cl3) engaged in the process permits access to both syn-aldol adducts. 相似文献
17.
Methods allowing control of stereoselectivity in aldol reactions of enolates derived from 1,3-dioxan-5-ones (4) are described. Boron enolates, generated in situ, react with benzaldehyde to give the corresponding anti aldol selectively (the anti:syn ratio of up to 96:4) and in high yield. Lithium enolates give high anti selectivity only with aldehydes branched at the alpha-position. Enantioselective deprotonation of C(S) symmetrical dioxanones (e.g., 4b) can be accomplished efficiently, with enantiomeric excess of up to 90%, with chiral lithium amide bases of general structure PhCH(Me)N(Li)R (9, 10) if the R group is sufficiently bulky (e.g, R = adamantyl) or is fluorinated (e.g., R = CH2CF3). Dioxanone boron and lithium enolates react readily with glyceraldehyde derivatives (19), yielding protected ketohexoses (20 and 21). 相似文献
18.
Direct asymmetric aldol reaction of aryl ketones with aryl aldehydes catalyzed by chiral metal complex is reported for the first time herein. Two novel semicrown chiral ligands 1a and 1b were synthesized from (S)- and (R)-BINOL, respectively, and then employed to catalyze the direct asymmetric aldol addition of aryl ketones to aryl aldehydes. Introduced with 2.0 equiv of diethylzinc, 1b had higher enantioselectivity than 1a. Up to 97% yield and up to 80% enantioselectivity were achieved. 相似文献
19.
A simple and commercially available chiral 1,2-diaminocyclohexane as catalyst, hexanedioic acid as co-catalyst could efficiently catalyze the asymmetric aldol reaction in MeOH-H2O. Cyclic ketones as aldol substrates gave the anti-β-hydroxyketone products with moderate to good yields, diastereoselectivity and enantioselectivity (up to 78% yield, >20:1 anti/syn, 94% ee). Hydroxyacetone as aldol substrate afforded the syn-α, β-dihydroxyketones as major products in up to 85% yield with good enantioselectivity (up to >20:1 syn/anti, 93% ee). 相似文献
20.
Alternative titanium-mediated aldol procedures based on several protected beta-hydroxy ethyl ketones have been surveyed. Eventually, enolization of (S)-1-benzyloxy-2-methyl-3-pentanone (1) with (i-PrO)TiCl3/i-Pr2NEt provided a very reactive enolate that afforded the corresponding 2,4-syn-4,5-syn aldol adducts in high yields and diastereomeric ratios with a broad range of aldehydes. 相似文献