Recent Advances in the Baylis−Hillman Reaction and Applications

The chemistry of copper is extremely rich because it can easily access Cu0, CuI, CuII, and CuIII oxidation states allowing it to act through one-electron or two-electron processes. As a result, both radical pathways and powerful two-electron bond forming pathways via organmetallic intermediates, similar to those of palladium, can occur. In addition, the different oxidation states of copper associate well with a large number of different functional groups via Lewis acid interactions or π-coordination. In total, these feature confer a remarkably broad range of activities allowing copper to catalyze the oxidation and oxidative union of many substrates.

Oxygen is a highly atom economical, environmentally benign, and abundant oxidant, which makes it ideal in many ways.1 The high activation energies in the reactions of oxygen require that catalysts be employed.2 In combination with molecular oxygen, the chemistry of copper catalysis increases exponentially since oxygen can act as either a sink for electrons (oxidase activity) and/or as a source of oxygen atoms that are incorporated into the product (oxygenase activity). The oxidation of copper with oxygen is a facile process allowing catalytic turnover in net oxidative processes and ready access to the higher CuIII oxidation state, which enables a range of powerful transformations including two-electron reductive elimination to CuI. Molecular oxygen is also not hampered by toxic byproducts, being either reduced to water, occasionally via H2O2 (oxidase activity) or incorporated into the target structure with high atom economy (oxygenase activity). Such oxidations using oxygen or air (21% oxygen) have been employed safely in numerous commodity chemical continuous and batch processes.3

However, batch reactors employing volatile hydrocarbon solvents require that oxygen concentrations be kept low in the head space (typically <5–11%) to avoid flammable mixtures, which can limit the oxygen concentration in the reaction mixture.4,5,6 A number of alternate approaches have been developed allowing oxidation chemistry to be used safely across a broader array of conditions. For example, use of carbon dioxide instead of nitrogen as a diluent leads to reduced flammability.5 Alternately, water can be added to moderate the flammability allowing even pure oxygen to be employed.6 New reactor designs also allow pure oxygen to be used instead of diluted oxygen by maintaining gas bubbles in the solvent, which greatly improves reaction rates and prevents the build up of higher concentrations of oxygen in the head space.4a,7 Supercritical carbon dioxide has been found to be advantageous as a solvent due its chemical inertness towards oxidizing agents and its complete miscibility with oxygen or air over a wide range of temperatures.8 An number of flow technologies9 including flow reactors,10 capillary flow reactors,11 microchannel/microstructure structure reactors,12 and membrane reactors13 limit the amount of or afford separation of hydrocarbon/oxygen vapor phase thereby reducing the potential for explosions.

Enzymatic oxidizing systems based upon copper that exploit the many advantages and unique aspects of copper as a catalyst and oxygen as an oxidant as described in the preceding paragraphs are well known. They represent a powerful set of catalysts able to direct beautiful redox chemistry in a highly site-selective and stereoselective manner on simple as well as highly functionalized molecules. This ability has inspired organic chemists to discover small molecule catalysts that can emulate such processes. In addition, copper has been recognized as a powerful catalyst in several industrial processes (e.g. phenol polymerization, Glaser-Hay alkyne coupling) stimulating the study of the fundamental reaction steps and the organometallic copper intermediates. These studies have inspiried the development of nonenzymatic copper catalysts. For these reasons, the study of copper catalysis using molecular oxygen has undergone explosive growth, from 30 citations per year in the 1980s to over 300 citations per year in the 2000s.

A number of elegant reviews on the subject of catalytic copper oxidation chemistry have appeared. Most recently, reviews provide selected coverage of copper catalysts14 or a discussion of their use in the aerobic functionalization of C–H bonds.15 Other recent reviews cover copper and other metal catalysts with a range of oxidants, including oxygen, but several reaction types are not covered.16 Several other works provide a valuable overview of earlier efforts in the field.17 This review comprehensively covers copper catalyzed oxidation chemistry using oxygen as the oxidant up through 2011. Stoichiometric reactions with copper are discussed, as necessary, to put the development of the catalytic processes in context. Mixed metal systems utilizing copper, such as palladium catalyzed Wacker processes, are not included here. Decomposition reactions involving copper/oxygen and model systems of copper enzymes are not discussed exhaustively. To facilitate analysis of the reactions under discussion, the current mechanistic hypothesis is provided for each reaction. As our understanding of the basic chemical steps involving copper improve, it is expected that many of these mechanisms will evolve accordingly.

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Aerobic Copper-Catalyzed Organic Reactions

Reactivity of Dioxygen−Copper Systems

The baylis-hillman reaction : a novel carbon-carbon bond forming reaction

2. Essential Components: Earlier Developments 5449 2.1. Activated alkenes/alkynes 5450 2.1.1. Acyclic activated alkenes/ alkynes 5450 2.1.2. Cyclic activated alkenes 5451 2.2. Electrophiles 5451 2.3. Catalysts 5452 3. Essential Components: Recent Developments 5452 3.1. Activated Alkenes/Alkynes 5452 3.2. Electrophiles 5460 3.3. Catalysts 5477 4. Asymmetric Baylis-Hillman Reaction: Earlier Developments 5495

Recent contributions from the Baylis-Hillman reaction to organic chemistry.

Enhancement of the Enantioselectivity in Lipase-Catalyzed Kinetic Resolutions of 3-Phenyl-2H-azirine-2-methanol by Lowering the Temperature to −40 °C

Asymmetric reduction of the prochiral carbonyl group of aliphatic .gamma.- and .delta.-keto acids by use of fermenting bakers' yeast

The stereoelectronic considerations and the molecular modeling using an X-ray structure of Rhizomucor miehei lipase suggested that the lipase-catalyzed reactions proceed under the stereoelectronic control. This suggestion was supported by the semiempirical MO (MNDO-PM3) calculations carried out on the imidazole-catalyzed transesterification as a model reaction. The stereoelectronic effect operates at the transition state (TS) more effectively than at the tetrahedral intermediate (THI). The stabilization energy due to the stereoelectronic effect operating at the TS was estimated to be ca. 5 kcal mol−1. The enantioselectivities for 1-phenylethanol, 1-phenyl-2-propanol, and 1-cyclohexylethanol were estimated in terms of the lipase-induced strain caused at the TS. A TS model generally applicable to chiral secondary alcohols is proposed. The kinetic study supported the TS model. The result that the enantioselectivity in the lipase-catalyzed transesterifications arises from the difference in Vmax between the tw...

Origin of the Enantioselectivity of Lipases Explained by a Stereo-Sensing Mechanism Operative at the Transition State

Low-temperature method for enhancement of enantioselectivity in the lipase-catalyzed kinetic resolutions of solketal and some chiral alcohols

DABCO-catalyzed condensations of ethyl 2,3-butadienoate (1a) with aldehydes at -6 to 25 o C gave 3-hydroxy-2-vinylidenealkanoates 3 in 41-54% yields. Butyllithium-promoted condensations of 1a with aldehydes at -105 to -70 o C afforded 3 in 56-67% yields. Reaction of ethyl 2,3-heradienoate (1k) with 1-heptanal in the presence of butyllithium gave ethyl 3-hydroxy-2-(1-butenylidene)nonanoate (3k) in 64% yield; however, when the butyllithium-promoted condensation of 1k with aldehydes was carried out at -90 to -70 o C and then treated in the same pot with wet THF for 11-27 h at room temperature, ethyl (E)-2-(1-alkynyl)-2-alkenoates 7 (12-36% yields) were obtained along with 3 (14-26% yields)

Masanori Utaka

Papers

Enhancement of the Enantioselectivity in Lipase-Catalyzed Kinetic Resolutions of 3-Phenyl-2H-azirine-2-methanol by Lowering the Temperature to −40 °C

Asymmetric reduction of the prochiral carbonyl group of aliphatic .gamma.- and .delta.-keto acids by use of fermenting bakers' yeast

Origin of the Enantioselectivity of Lipases Explained by a Stereo-Sensing Mechanism Operative at the Transition State

Low-temperature method for enhancement of enantioselectivity in the lipase-catalyzed kinetic resolutions of solketal and some chiral alcohols

A new aldol condensation of .alpha.-allenic esters with aldehydes, including a one-pot synthesis of enyne compounds