有机小分子催化的不对称羟醛缩合反应

总结了近年来用于不对称催化羟醛缩合反应的各种有机小分子催化剂, 简要阐述了每种类型的催化剂的催化机理以及它们的优缺点, 同时对有机小分子催化反应的发展进行了展望.     

Protonated chiral prolinamide catalyzed enantioselective direct aldol reaction in water

Protonated chiral prolinamide organocatalysts have been shown to catalyze an enantioselective direct aldol process in water to provide the aldol product in high yield and good enantioselectivity. The two diastereomeric catalysts (S,R)-4b and (S,S)-4c show different reactivity.     

Role of Adamantane Amide Based on L-Proline Double-H Potential Organocatalyst in Aldol Reaction with Product Separated via Host-guest Interaction

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.     

脯氨酸二肽催化的不对称直接Aldol反应

以(S)-脯氨酸和(R)-脯氨酸为原料合成了二肽H-(S)-Pro-(S)-Pro-OH(1)和H-(S)-Pro(-R)-Pro-OH(2),分别以两种二肽催化了不对称直接A ldol反应,获得了相同立体构型(S)的产物,与(S)-脯氨酸催化所得的产物构型(R)相反.该催化剂的立体选择性不高(ee<21%).理论计算的结果与实验结果吻合.     

Proline-based Amino Pyridine Dipeptides as Efficient Organocatalysts for Direct Aldol Reaction

A series of proline-based amino pyridine dipeptide organocatalysts was synthesized and applied in direct asymmetric intermolecular aldol reaction. These catalysts showed good solubility in organic solvents, good yields (73%―97%) and enantioselectivitives(74%―94%). Among them, dipeptide organocatalyst(2) was found to be the most efficient one for the asymmetric aldol reaction between cyclohexanone and 4-nitrobeznaldehyde. After optimizing the catalytic reaction conditions, we found that the catalyst showed high yield(97%), enantioselectivity(e.e., up to 92%) and anti-diastereoselectivity(up to 95:5) at mild room temperature without any additives.     

Gelatin Protein‐Mediated Direct Aldol Reaction

Gelatin protein was found to catalyze the aldol reaction between cyclohexanone and different aromatic aldehydes under mild reaction conditions. The aldol additions carried out in DMSO at 37° yielded the addition products with moderate diastereoselectivities favoring the syn isomers. Appropriate control experiments demonstrated the activity of the protein in the aldol reaction. The kinetic study of the model reaction between 4‐nitrobenzaldehyde and cyclohexanone established a first‐order rate constant k=(7.4±0.5)×10^?3 h^?1. Moreover, the scale‐up of the process was successfully achieved at 1‐g scale in a yield comparable to that in small scale.     

Chiral Diamine-catalyzed Asymmetric Aldol Reaction

A highly efficient catalytic system composed of a simple and commercially available chiral primary diamine (1R,2R)-cyclohexane-1,2-diamine(6) and trifluoroacetic acid (TFA) was employed for asymmetric Aldol reaction in em-PrOH at room temperature. A loading of 10%(molar fraction) catalyst 6 with TFA as a cocatalyst could catalyze the Aldol reactions of various ketones or aldehydes with a series of aromatic aldehydes, furnishing Aldol pro- ducts in moderate to high yields(up to >99%) with enantioselectivities of up to >99% and diastereoselectivities of up to 99:1.     

L-脯氨酸催化的不对称Aldol缩合反应实验设计

介绍了L-脯氨酸催化的对硝基苯甲醛与丙酮的不对称Aldol反应的实验设计。室温反应2 h后,柱层析得到（R）-4-（4-硝基苯基）-4-羟基-2-丁酮,利用手性高效液相色谱测试得到产物的ee值。学生实验结果显示,收率范围为53%~74%,对映选择性范围为62%~69%。本实验方案将Aldol反应的研究成果设计成综合性实验,不仅强化训练了学生基本的实验技能和操作,同时拓宽了知识面,培养了学生分析问题、解决问题等方面的综合能力。     

Asymmetric Hydrative Aldol Reaction (HAR) via Vinyl-Gold Promoted Intermolecular Ynamide Addition to Aldehydes

Herein, we reported an intermolecular asymmetric hydrative aldol reaction through vinyl-gold intermediate under ambient conditions. This tandem alkyne hydration and sequential nucleophilic addition afforded a “base-free” approach to β-hydroxy amides with high efficiency (up to 95 % yields, >50 examples). Vinyl gold intermediate was applied as reactive nucleophile and Fe(acac)₃ was used as the critical co-catalyst to prevent undesired protodeauration, allowing this transformation to proceed under mild conditions with good functional group tolerance and excellent stereoselectivity (>20 : 1 d.r. and up to 99 % ee).     

Direct Asymmetric Aldol Reaction Co-catalyzed by Amphiphilic Prolinamide Phenol and Lewis Acidic Metal on Water

An approach based on combinations of various water compatible Lewis acids and lipophilic group containing amphiphilic prolinamide co‐catalysts has been evaluated for the direct asymmetric Aldol reaction. From the broad screening of chloride salts from alkali metal to transition metal, LiCl, ZnCl₂ and SnCl₂ lead to the highest stereoselectivities. The optimized catalytic conditions (10 mol% prolinamide with 10 mol% MCl₂ or 20 mol% LiCl at room temperature on water) gave anti‐products with improved enantioselectivities (up to 99% ee) compared to the moderately stereoselective procedure based on prolinamide activation only.     

Novel Polycarbonate Copolymer as Organocatalyst for Aldol and Michael Reaction

A new polymeric organocatalyst is prepared by free radical copolymerization of allyl diglycol carbonate (ADC) and Boc-protected allyl prolinate and evaluated as a chiral catalyst for aldol and Michael reaction.     

Aldol Condensation for the Construction of Organic Functional Materials

Aldol condensation is a cost-effective and sustainable synthetic method, offering the advantages of low complexity, substrate universality, and high efficiency. Over the past decade, it has become popular for creating next-generation organic functional materials, particularly rigid-rod conjugated (semi)conductors. This review focuses on conjugated small molecules, oligomers, and polymeric (semi)conductors synthesized through aldol condensation, with emphasis on their remarkable features in advancing n-type organic field-effect transistors (OFETs), organic electrochemical transistors (OECTs), organic photovoltaics (OPVs), and organic thermoelectrics (OTEs) as well as NIR-II photothermal conversion. Coherence character, optical properties, microstructure, and chain conformation are investigated to understand material-property relationships. Future applications and challenges in this area are also discussed.     

Total Synthesis of Lucidumone through Convenient One-pot Preparation of the Tetracyclic Skeleton by Claisen Rearrangement and Subsequent Intramolecular Aldol Reaction

The total synthesis of lucidumone ( 1 ), a Ganoderma meroterpenoid, was accomplished in racemic form from easily prepared 6 and 7 in 10 steps as the longest linear sequence. The synthesis was completed through one-pot preparation of the tetracyclic core skeleton by Claisen rearrangement followed by an intramolecular aldol reaction. The intramolecular aldol reaction allowed for the stereocontrolled construction of the bicyclo [2.2.2] octane skeleton fused to an indanone structure. The enantioselective total synthesis of 1 was also described via a chiral transfer strategy in the Claisen rearrangement.     

聚氯乙烯负载L-脯氨酸催化不对称Aldol反应的研究

以聚氯乙烯为载体,合成两种负载型催化剂水解聚氯乙烯四乙烯五胺负载L-脯氨酸催化剂(HPTP)和聚氯乙烯四乙烯五胺负载L-脯氨酸催化剂(PTP),催化剂中脯氨酸负载量分别为2.46 mmol/g和1.52 mmol/g。两种催化剂均可实现对不对称Aldol反应的催化,但HPTP的活性和选择性均较PTP的高。HPTP在水中可以催化多种苯甲醛与丙酮的不对称Aldol反应,取得中等的ee值。HPTP经过回收还可以重复利用,显示了较好的性能。在合适的反应条件下,HPTP催化对硝基苯甲醛和丙酮的反应,获得最高75%的产率和39%的ee值。     

脯氨酸催化丙酮与异丁醛不对称直接Aldol反应的DFT研究

采用密度泛函DFT-B3LYP方法计算研究了(S)-脯氨酸催化丙酮和异丁醛的不对称直接羟醛缩合(A l-dol)反应,得到了两种烯胺中间体及立体控制步骤中的四个立体异构过渡态的优化构型和相对能量,解释了该不对称反应的立体选择性.     

杂双金属复合物ZABDP催化芳香酮与芳香醛的直接不对称Aldol反应

合成了新型的手性铝/锌杂双金属复合物(R,S,S)-3,3'-二[(N-二苯基脯氨醇)甲基]-2,2'-二羟基-1,1'-联萘酚铝/锌复合物(ZABDP).在催化芳香酮与芳香醛的羟醛缩合(Aldol)反应中,该复合物中的铝作为路易斯酸活化醛,锌的烷氧化物作为Br?nsted碱,使苯乙酮形成活性锌的烯醇化物,2种金属的应用使得芳香醛与芳香酮的直接不对称Aldol反应顺利进行,反应的对映选择性最高达90%,产率最高达99%.     

Catalytic Microwave-Promoted Direct Aldol Condensation Using Resin-Bound Secondary Amine

A series of polystyrene-supported imino group-bearing catalysts were prepared. A highly efficient combination of recyclable catalysts and microwave irradiation was developed as a green protocol for the direct aldol reaction. Notably, microwaves greatly shorten the reaction times to only 20 min and improve the yield significantly. Catalyst loading was reduced as well. Different aromatic aldehydes as aldol donors were subjected to our catalyst system and afforded the corresponding products in satisfactory yields. Additionally, the polymer-supported catalysts could be recovered by simple filtration and were reusable for at least four times without significant loss of reactivity.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

氟分子与乙烯反应的直接动力学模拟

Direct dynamics within the framework of DFT was used to study the long-time puzzling mechanism of the reaction between F2 and ethylene. Three types of reactions are widely accepted : F atom elimination reaction, HF elimination reaction and the addition reaction. Several reaction mechanisms have been proposed, but only the radical mechanism can reasonably explain the initial reaction at low temperature. In this article, our calculations support the radical mechanism and the reaction mechanisms of the three reactions, and they are described in detail by trajectory simulation. The reactions in a cryogenic matrix with the reaction mechanism were also discussed.     

Directed Aldol Condensations

The present article describes the discovery of a new procedure for aldol condensations for the preparation of α,β-unsaturated carbonyl compounds

1 G. Wittig, H. Pommer, and W. Stilz, German Patent 1199252 (April 5, 1963), BASF; Chem. Abstr. 63, P 1739c (1965).

. The scope of this process is demonstrated by many examples, including some from the natural products sector; at the same time, however, these examples also mark its limitations. The metalated Schiff's bases may be classified as ambident anions; this also explains acylations on the nitrogen. A comparison of the new directed aldol condensation with the formation of unsaturated carbonyl compounds through olefination via phosphorylids shows that the latter method fails when a ketone is used as the substrate. This is where the described procedure using metalated Schiff's bases proves its value.     

(4S)-苯氧基-(S)-脯氨酸催化直接不对称羟醛缩合反应

N-乙氧羰基-(4R)-羟基-(S)-脯氨酸甲酯与苯酚的Mitsunobu反应给出N-乙氧羰基-(4S)-苯氧基-(S)-脯氨酸甲酯,后者经皂化和盐酸水解后得标题氨基酸.这一化合物(5 mol%)对映选择性催化丙酮和取代苯甲醛的羟醛缩合反应,产率67.4%～89.9%,ee最高达76.5%.