Asymmetric Organocatalyzed Michael Addition of Nitromethane to a 2‐Oxoindoline‐3‐ylidene Acetaldehyde and the Three One‐Pot Sequential Synthesis of (−)‐Horsfiline and (−)‐Coerulescine

(?)‐Horsfiline and (?)‐coerulescine were synthesized through three one‐pot operations in 33 and 46 % overall yield, respectively. Key to the success was the efficient use of a diarylprolinol silyl ether to catalyze the asymmetric Michael addition of nitromethane to a 2‐oxoindoline‐3‐ylidene acetaldehyde. This allowed the all‐carbon quaternary, spirocyclic carbon stereocenter to be constructed in good yield with excellent enantioselectivity.     

One‐Pot Synthesis of (−)‐Oseltamivir and Mechanistic Insights into the Organocatalyzed Michael Reaction

The one‐pot sequential synthesis of (?)‐oseltamivir has been achieved without evaporation or solvent exchange in 36 % yield over seven reactions. The key step was the asymmetric Michael reaction of pentan‐3‐yloxyacetaldehyde with (Z)‐N‐2‐nitroethenylacetamide, catalyzed by a diphenylprolinol silyl ether. The use of a bulky O‐silyl‐substituted diphenylprolinol catalyst, chlorobenzene as a solvent, and HCO₂H as an acid additive, were key to produce the first Michael adduct in both excellent yield and excellent diastereo‐ and enantioselectivity. Investigation into the effect of acid demonstrated that an acid additive accelerates not only the E–Z isomerization of the enamines derived from pentan‐3‐yloxyacetaldehyde with diphenylprolinol silyl ether, but also ring opening of the cyclobutane intermediate and the addition reaction of the enamine to (Z)‐N‐2‐nitroethenylacetamide. The transition‐state model for the Michael reaction of pentan‐3‐yloxyacetaldehyde with (Z)‐N‐2‐nitroethenylacetamide was proposed by consideration of the absolute configuration of the major and minor isomers of the Michael product with the results of the Michael reaction of pentan‐3‐yloxyacetaldehyde with phenylmaleimide and naphthoquinone.     

One‐Pot Consecutive Catalysis by Integrating Organometallic Catalysis with Organocatalysis

The present study integrates two types of catalysis, namely, organometallic catalysis and organocatalysis in one reaction pot. In this process, the product of the first catalytic cycle acts as catalytic component for next catalytic cycle. The abnormal N‐heterocyclic carbene–copper‐based organometallic catalyst acts as an efficient catalyst for a click reaction to provide triazole, which, in turn, acts as an efficient organocatalyst for different organic transformations, for example, aza‐Michael addition and multicomponent reactions, in a consecutive fashion in the same reaction pot.     

A simple recipe for sophisticated cocktails: organocatalytic one-pot reactions--concept, nomenclature, and future perspectives

Asymmetric organocatalysis has been successfully incorporated in many multistep one-pot sequences to provide simple access to structurally complex target molecules in a highly stereoselective fashion. The key feature behind this success is the ability of organocatalyzed reactions to proceed efficiently in the presence of large amounts of spectator reagents. Additionally, owing to their organic nature and substoichiometric presence, organocatalysts are also expected to become innocent bystanders in subsequent transformations. In this Minireview, an easy-to-use classification and nomenclatural system that is capable of systematically and informatively describing each one-pot reaction is introduced, and selected important contributions within the field of organocatalytic one-pot reactions are reviewed according to this new system. Finally, future developments and perspectives in the field are discussed.     

"一锅法"合成戊二烯甲酯

以丙烯醛和丙二酸为原料,经缩合反应制得戊二烯酸,产率52．2％。采用“一锅法”合成了戊二烯酸甲酯,产率52．8％。其结构经^1H NMR和IR确证。     

One‐Pot Synthesis of Pentasubstituted Cyclohexanes by a Michael Addition Followed by a Tandem Inter–Intra Double Henry Reaction

Michael, Henry, and Henry : A new one‐pot reaction of α,β‐unsaturated aldehydes and β‐dicarbonyls, which involves a Michael reaction catalyzed by diarylprolinol ethers and an inter–intramolecular Henry tandem reaction catalyzed by TBAF (see scheme), has been developed. The reaction proceeds in high enantio‐ and diastereoselectivity for a wide range of unsaturated aldehydes and β‐dicarbonyl reagents.

     

Synthesis of the Heparin‐Based Anticoagulant Drug Fondaparinux

Fondaparinux, a synthetic pentasaccharide based on the heparin antithrombin‐binding domain, is an approved clinical anticoagulant. Although it is a better and safer alternative to pharmaceutical heparins in many cases, its high cost, which results from the difficult and tedious synthesis, is a deterrent for its widespread use. The chemical synthesis of fondaparinux was achieved in an efficient and concise manner from commercially available D ‐glucosamine, diacetone α‐D ‐glucose, and penta‐O‐acetyl‐D ‐glucose. The method involves suitably functionalized building blocks that are readily accessible and employs shared intermediates and a series of one‐pot reactions that considerably reduce the synthetic effort and improve the yield.     

Enantioselective Synthesis of (−)‐Halenaquinone

The efficient, 12–14 step (LLS) total synthesis of (?)‐halenaquinone has been achieved. Key steps in the synthetic sequence include: (a) proline sulfonamide‐catalyzed, Yamada–Otani reaction to establish the C6 all‐carbon quaternary stereocenter, (b) multiple, novel palladium‐mediated oxidative cyclizations to introduce the furan moiety, and (c) oxidative Bergman cyclization to form the final quinone ring.     

One‐Pot Organocatalytic Asymmetric Synthesis of 3‐Nitro‐1,2‐dihydroquinolines by a Dual‐Activation Protocol

Generally, amine‐catalyzed enantioselective transformations rely on chiral enamine or unsaturated iminium intermediates. Herein, we report a protocol involving dual activation by an aromatic iminium and hydrogen‐bonding. An enantioselective aza‐Michael–Henry domino reaction of 2‐aminobenzaldehydes with nitroolefins has been developed through this protocol using primary amine thiourea catalysts to provide a variety of 3‐nitro‐1,2‐dihydroquinolines in moderate yields and with up to 90 % ee. The mechanism for the catalytic enantioselective reaction was confirmed by ESI mass spectrometric detection of the reaction intermediates. The products formed are substructures found in skeletons of important biological and pharmaceutical molecules.     

Asymmetric Triple Relay Catalysis: Enantioselective Synthesis of Spirocyclic Indolines through a One‐Pot Process Featuring an Asymmetric 6π Electrocyclization

A rare example of a one‐pot process that involves asymmetric triple relay catalysis is reported. The key step is an asymmetric [1,5] electrocyclic reaction of functionalized ketimines. The substrates for this process were obtained in situ in a two‐step process that involved the hydrogenation of nitroarenes with a Pd/C catalyst to yield aryl amines and their subsequent coupling with isatin derivatives in a Brønsted acid catalyzed ketimine formation reaction. The electrocyclization was catalyzed by a bifunctional chiral Brønsted base/hydrogen bond donor catalyst. The one‐pot process gave the desired products in good yields and with excellent enantioselectivity.     

Asymmetric synthesis of β-adrenergic blockers through multistep one-pot transformations involving in situ chiral organocatalyst formation

Two birds one stone: A new atom-economical one-pot approach to enantioselective chiral drug synthesis, involving in situ multistep organocatalyst formation and the application of the reaction for multistep sequential synthesis of β-adrenergic blockers is disclosed (see scheme).     

One‐Pot Protection‐Glycosylation Reactions for Synthesis of Lipid II Analogues

(2,6‐Dichloro‐4‐methoxyphenyl)(2,4‐dichlorophenyl)methyl trichloroacetimidate ( 3 ) and its polymer‐supported reagent 4 can be successfully applied to a one‐pot protection‐glycosylation reaction to form the disaccharide derivative 7 d for the synthesis of lipid II analogues. The temporary protecting group or linker at the C‐6 position and N‐Troc protecting group of 7 d can be cleaved simultaneously through a reductive condition. Overall yields of syntheses of lipid II ( 1 ) and neryl‐lipid II N^ε‐dansylthiourea are significantly improved by using the described methods.     

A One‐Pot O‐Phosphinative Passerini/Pudovik Reaction: Efficient Synthesis of Highly Functionalized α‐(Phosphinyloxy)amide Derivatives

A one‐pot O‐phosphinative Passerini/Pudovik reaction has been developed, based on reacting aldehydes, isocyanides, and phosphinic acids followed by the addition of second aldehydes to form the corresponding α‐(phosphinyloxy)amide derivatives. This is the first reported instance of a Passerini‐type, isocyanide‐based multicomponent reaction using a phosphinic acid instead of a carboxylic acid. The nucleophilicity of the phosphinate group allows a subsequent catalytic Pudovik‐type reaction, affording the highly functionalized α‐(phosphinyloxy)amide derivative in high yield. A wide range of aldehydes and isocyanides are applicable to this reaction.