Mukaiyama-Michael Reaction Research Articles

Novel C2-symmetric chiral O,N,N,O-tetradentate 2,2-bipyridyldiolpropane ligands: synthesis and application in asymmetric diethylzinc addition to aldehydes

First synthesis of C2-symmetric chiral O,N,N,O-tetradentate 2,2-bipyridyldiolpropane ligands is described. The Mukaiyama–Michael reaction was applied as an important reaction for the synthesis of 2,2-bipyridylpropane 9. Among the ligands synthesized, ligand 11 exhibits excellent chiral induction (up to 97% ee) in diethylzinc addition to various aldehydes. The use of additional Lewis acid such as Ti(OiPr)4 in diethylzinc addition reaction is not required for the present catalytic system.

Support Effect on Stereoselectivities of Vinylogous Mukaiyama–Michael Reactions Catalyzed by Immobilized Chiral Copper Complexes

Chiral bis(oxazoline)- and azabis(oxazoline)-copper complexes, used as homogeneous catalysts or immobilized onto laponite, are able to catalyze vinylogous Mukaiyama–Michael reactions between 2-(trimethylsilyloxy)furan and several electron-deficient alkenes. A study of the support effect has been conducted and different changes on the diastereoselectivities and enantioselectivities has been observed. The behavior of the catalyst is different, depending on the structure of the substrate (Michael acceptor). When diethyl benzylidenemalonate was used, the major diastereomer was that with syn configuration, but the homogeneous and the heterogeneous catalysts lead to opposite enantiomers (−80% ee in solution and 38% ee in the heterogeneous phase). This change represents a support effect of ∼1.8 kcal/mol. With N-(E)-but-2-enoyloxazolidinone, the most relevant change is in the diastereomer preference. In solution, the anti isomer is the major one (anti/syn = 98/2); however, in contrast, syn isomer is preferred wit...

ChemInform Abstract: Enantioselective Mukaiyama—Michael with 2‐Enoyl Pyridine N‐Oxides Catalyzed by PYBOX‐DIPH‐Zn(II)‐Complexes at Ambient Temperature.

A chiral PYBOX-DIPH-Zn(II) catalyzed enantioselective Mukaiyama–Michael reaction of acyclic silyl enol ethers with 2-enoylpyridine N-oxides has been studied in external additive free conditions at ambient temperature. The methodology offers straightforward access to a variety of functionalized chiral 1,5-dicarbonyl compounds, which could easily be elaborated into synthetically viable pyrones via hydrolysis followed by cyclization. A transition state model has been proposed to explain the stereochemical outcome.

Mukaiyama–Michael Reactions with Acrolein and Methacrolein: A Catalytic Enantioselective Synthesis of the C17–C28 Fragment of Pectenotoxins

Mukaiyama–Michael Reactions with Acrolein and Methacrolein: A Catalytic Enantioselective Synthesis of the C17–C28 Fragment of Pectenotoxins

ChemInform Abstract: Enantioselective Mukaiyama—Michael Reaction of Silyl Enol Ethers to 2‐Enoylpyridine N‐Oxides Catalyzed by Copper‐Bis(oxazoline) Complex.

AbstractA variety of silyl enol ethers such as (II) undergo Michael addition with 2‐enoylpyridine N‐oxides (I) to furnish the corresponding Michael adducts (III) in high yields and enantioselectivities.

ChemInform Abstract: Organocatalytic, Highly Enantioselective Vinylogous Mukaiyama—Michael Reaction of Acyclic Dienol Silyl Ethers.

AbstractThis reaction is accomplished for the first time.

Enantioselective Mukaiyama–Michael Reaction of Silyl Enol Ethers to 2‐Enoylpyridine N‐Oxides Catalyzed by Copper‐ Bis(oxazoline) Complex

AbstractA catalytic enantioselective Mukaiyama–Michael reaction of 2‐enoylpyridine N‐oxides has been developed using a simple bis(oxazoline)‐copper complex. A variety of silyl enol ethers undergo smooth Michael addition with 2‐enoylpyridine N‐oxides to furnish the corresponding Michael adducts in high yields with high enantioselectivities (up to 97% ee).

Enantioselective Mukaiyama–Michael with 2-enoyl pyridine N-oxides catalyzed by PYBOX-DIPH-Zn(ii)-complexes at ambient temperature

A chiral PYBOX-DIPH-Zn(II) catalyzed enantioselective Mukaiyama-Michael reaction of acyclic silyl enol ethers with 2-enoylpyridine N-oxides has been studied in external additive free conditions at ambient temperature. The methodology offers straightforward access to a variety of functionalized chiral 1,5-dicarbonyl compounds, which could easily be elaborated into synthetically viable pyrones via hydrolysis followed by cyclization. A transition state model has been proposed to explain the stereochemical outcome.

Iodine catalyzed Mukaiyama–Michael reaction: experimental evaluation of catalytic effect in conjunction with computational study of the reaction mechanism

The catalytic effect of iodine on Mukaiyama–Michael reaction has been evaluated experimentally taking three representative silyl enolates, which react effectively with various α,β‐unsaturated ketones in the presence of 10 mol% of iodine giving 1,5‐dicarbonyl products in 74%–87% yield. A study on the mechanism of the iodine catalyzed reaction has been carried out by density functional theory at the Becke, three‐parameter, Lee–Yang–Parr/6‐31G* level considering trihydrosilyl enol ether and acrolein as model system. Although the uncatalyzed reaction occurs through an asynchronous concerted bond formation process, two energetically competitive pathways (one concerted and the other stepwise) are possible for the catalyzed process. Iodine catalyzed MM reaction between methyl vinyl ketone and 1‐phenyl‐1‐(trimethylsilyloxy)‐ethylene involves a very low activation barrier compared with that of the simple trihydrosilyl enol ether/acrolein system. Catalytic effect of iodine was further confirmed by highest occupied molecular orbital–lowest unoccupied molecular orbital analysis and reactivity analysis using conceptual density functional theory based reactivity descriptors at Becke, three‐parameter, Lee–Yang–Parr/6‐31G** level. Copyright © 2012 John Wiley & Sons, Ltd.

Organocatalytic, Highly Enantioselective Vinylogous Mukaiyama–Michael Reaction of Acyclic Dienol Silyl Ethers

Now also acyclic: The first catalytic, enantioselective, vinylogous Michael reaction of linear, acyclic dienol silyl ethers was achieved. The reaction, based upon the principle of iminium ion catalysis, delivered 1,7-dioxo compounds in one step with good yields, complete regio-, and excellent enantioselectivity. γ-Substituted dienol silyl ethers furnished products with two new stereogenic centers with good diastereoselectivity. Ms = mesityl, PNBA = para-nitrobenzoic acid.

Mukaiyama–Michael Reactions with Acrolein and Methacrolein: A Catalytic Enantioselective Synthesis of the C17–C28 Fragment of Pectenotoxins

Enantioselective iminium-catalyzed reactions with acrolein and methacrolein are rare. A catalytic enantioselective Mukaiyama-Michael reaction that readily accepts acrolein or methacrolein as substrates, affording the products in good yields and 91-97% ee, is presented. As an application of the methodology, an enantioselective route to the key C17-C28 segment of the pectenotoxin using the Mukaiyama-Michael reaction as the key step is described.

Michael addition/pericyclization/rearrangement – a multicomponent strategy for the synthesis of substituted resorcinols

The combination of methyl 3,7-dioxo-2-diazo-4-octenoate from the zinc triflate catalyzed Mukaiyama-Michael reaction of methyl 3-tert-butylsilyloxy-2-diazobutenoate and 4-methoxy-3-buten-2-one with Michael acceptors (methyl vinyl ketone, N-phenylmaleimide, β-nitrovinylarenes) in the presence of a catalytic amount of base provides convenient access to highly substituted resorcinol derivatives. This transformation is achieved in an efficient one-pot multi-component transformation by the sequential addition of the reagents.

ChemInform Abstract: Highly Enantioselective Synthesis of γ‐Substituted Butenolides via the Vinylogous Mukaiyama—Michael Reaction Catalyzed by a Chiral Scandium(III)‐N,N′‐dioxide Complex.

AbstractThe e.e.

ChemInform Abstract: Vinylogous Mukaiyama—Michael Reactions Between 2‐Silyloxyfurans and Cyclic Enones or Unsaturated Oxo Esters.

AbstractIn the presence of SnCl4, cyclic enones and silyloxyfurans (II) undergo vinylogous Mukaiyama—Michael reactions to afford γ‐butenolides preferentially with anti stereoselectivity.

Highly enantioselective synthesis of γ-substituted butenolides via the vinylogous Mukaiyama–Michael reaction catalyzed by a chiral scandium(iii)–N,N′-dioxide complex

A highly efficient catalytic asymmetric vinylogous Mukaiyama-Michael reaction of the 2-silyloxyfuran with chalcone derivatives, catalyzed by a chiral N,N'-dioxide-scandium(III) complex, has been accomplished which tolerates a wide range of substrates. The reaction proceeds with complete regioselectivities, excellent diastereoselectivities (up to >99 : 1 dr) and good to excellent enantioselectivities (up to 94% ee) under mild conditions, delivering highly functionalized enantiomerically enriched anti-γ-substituted butenolides. The process is air-tolerant and easily manipulated with available reagents. In order to illustrate the synthetic potential of this reaction, the gram-scale synthesis and the elaboration of the butenolides have been explored. On the basis of the experimental results, a possible catalytic cycle and favorable stereorecognition model have been proposed.

ChemInform Abstract: First Sequential Mukaiyama—Michael Reaction/Crossed‐Claisen Condensation Using Two Molar Ketene Silyl Acetals and One Molar α,β‐Unsaturated Esters Promoted by a NaOH Catalyst.

AbstractA sequential Mukaiyama—Michael reaction and regioselective crossed‐Claisen condensation to afford 1,3,7‐tricarbonyl scaffolds is developed using two equivalents of ketene silyl acetals (II)/(IV) and one equivalent α,β‐unsaturated esters (I) in either a stepwise or one‐pot procedure.

A Short, Catalytic, Asymmetric Synthesis of Diospongins A and B by a One‐Pot, Sequential Hetero‐Diels–Alder/Mukaiyama–Michael Reaction Process

AbstractA new route to the diarylheptanoid diospongins A and B was developed. The key step is a novel, one‐pot, sequential dirhodium(II) tetrakis[(S)‐3‐(benzo‐fused phthalimido)‐2‐piperidinonate] [Rh2(S‐BPTPI)4] catalyzed enantioselective hetero‐Diels–Alder/TMSOTf‐catalyzed Mukaiyama–Michael reaction process. The sign of the optical rotation of natural diospongin B was determined to be (+) and not (–) as was originally reported.

ChemInform Abstract: Development of N,N‐Bis(perfluoroalkanesulfonyl)squaramides as New Strong Broensted Acids and Their Application to Organic Reactions.

AbstractN,N′‐Bis(triflyl)squaramide (Ia) is prepared and successfully applied in various Mukaiyama and Mukaiyama—Michael reactions.

Vinylogous Mukaiyama–Michael Reactions between 2‐Silyloxyfurans and Cyclic Enones or Unsaturated Oxo Esters

AbstractLewis acid catalyzed vinylogous Mukaiyama–Michael (VMM) reactions between 2‐(trialkylsilyloxy)furans 1 and α,β‐unsaturated cyclic enones 2 or oxo esters 4 have been investigated. Both substrates proved to be useful Michael acceptors in the title reaction, giving the butenolides 3 and 5 in good yields. A comparative study between the α,β‐unsaturated cyclic enones 2 and the oxo esters 4 as Michael acceptors showed better diasterecontrol with the latter class of compounds. In both series, crystal structures of the major isomers revealed anti relationships of newly formed stereogenic centers. From these data, two types of transition states could be proposed: an open TS with antiperiplanar orientation or a Diels–Alder‐like TS with exo approach.

ChemInform Abstract: The Mukaiyama Aldol and Mukaiyama—Michael Reactions Promoted by Commercially Available Molecular Sieves.

AbstractThe Mukaiyama aldol reactions of aldehydes (I) and (IV) with silyl ketene acetals or silyl enol ethers (II) proceed smoothly in the presence of pulverized mol.