l-Proline amides catalyze direct asymmetric aldol reactions of aldehydes with methylthioacetone and fluoroacetone

Direct aldol reactions of aldehydes with methylthio- and fluoroacetone catalyzed by proline amides have been investigated. l-Prolinamide 5e was found to be the best catalyst. Under the optimized reaction conditions, a series of aromatic and aliphatic aldehydes reacted smoothly with methylthioacetone, to generate 1-methylthio-4-hydroxyketones 3 in good yields and with high regio- and enantioselectivities. Excellent enantioselectivities of up to 98% ee were observed for aromatic aldehydes and even higher enantioselectivities of >99% ee were observed for aliphatic aldehydes. Asymmetric direct aldol reactions of fluoroacetone with aldehydes in the presence of 20 mol % of 5e preferentially occurred at the fluoromethyl group, yielding products with high enantioselectivities (up to 98% ee).     

Me3Ga-mediated alkynylation of aldehydes

The trimethylgallium reagent was found to promote the addition of phenylacetylene to various aromatic and aliphatic aldehydes. This reaction was efficiently carried out in anhydrous CH₂Cl₂ at room temperature under mild conditions and the corresponding propargylic alcohols were obtained in good to excellent yields up to 98%.     

Highly enantioselective hetero- Diels-Alder reaction of trans-1-methoxy- 2-methyl-3-trimethylsiloxybuta-1,3-diene with aromatic and aliphatic aldehydes catalyzed by 3-substituted BINOL-titanium complex

3-diphenylhydroxymethyl-substituted BINOL-titanium complex prepared in situ was found to be a highly efficient catalyst for hetero-Diels-Alder reaction of diene 1 with both aromatic and aliphatic aldehydes to give 2,5-disubstituted dihydropyrone in up to 99% yield and 99% ee.     

Direct organocatalytic asymmetric epoxidation of α,β-unsaturated aldehydes

The organocatalytic asymmetric epoxidation of α,β-unsaturated aldehydes with peroxides or sodium percarbonate is presented. Chiral pyrrolidine derivatives, proline and amino acid derived imidazolidinones mediate the asymmetric epoxidation of α,β-unsaturated aldehydes. For example, commercially available protected α,α-diphenyl-2-prolinol catalyzes the asymmetric formation of 2-epoxy-aldehydes in 81-95% conversion with up to 96:4 dr and 98% ee. The use of non-toxic catalysts, aqueous solvents and hydrogen peroxide or sodium percarbonate as the oxygen sources makes the reaction environmentally benign.     

多相CeO2催化剂上氧化吲哚与醛的选择性C3烯基化反应

本文报道了将市售CeO2作为一种高活性和可重复使用的催化剂用于无溶剂条件下氧化吲哚与醛的C3选择性烷基化反应.这种催化方法一般适用于不同的芳香族和脂肪族醛,得到3-烷基二烯-辛醇,产率高(87%–99%),立体选择性高(79%–93%为E-异构体).这是从氧化吲哚与各种脂肪族醛催化合成3-烯基氧化吲哚的首例.采用原位红外光谱研究了CeO2上Lewis酸位点与苯甲醛之间的Lewis酸-碱相互作用.不同粒径CeO2催化剂的构效关系研究表明,无缺陷CeO2表面是该反应的活性中心.     

Highly enantioselective phenylacetylene additions to both aliphatic and aromatic aldehydes

The readily available and inexpensive BINOL in combination with Ti(O(i)Pr)(4) is found to catalyze the reaction of an alkynylzinc reagent with various types of aldehydes including aliphatic aldehydes, aromatic aldehydes, and other alpha,beta-unsaturated aldehydes to generate chiral propargyl alcohols with 91-99% ee at room temperature. No previous chiral catalysts have exhibited such a broad scope of enantioselectivity with respect to the type of aldehydes for this reaction. [reaction: see text]     

Catalytic enantioselective addition of diethylzinc to aldehydes using aziridine based chiral ligands

The readily available ferrocenyl substituted aziridinylmethanol 1 (FAM-1) was used as a chiral catalyst in the diethylzinc addition reaction to aromatic and aliphatic aldehydes to give secondary alcohols in high yields and up to 99% enantiomeric excess at room temperature. The catalyst can be recovered and used without losing its activity.     

Comparaison entre le role de l'eau et celui d'un ether couronne dans le cadre de la reaction de wittig realisee en milieu heterogene : liquide-solide

The similar results issued from the use of water and the 18-crown 6 ether for the Wittig reaction (in liquid-solid two-phase systems) allowed us to obtain very high yields in olefin starting from aromatic as well as aliphatic aldehydes.     

A SeCSe-Pd(II) pincer complex as a highly efficient catalyst for allylation of aldehydes with allyltributyltin

An air- and moisture-stable SeCSe-Pd(II) pincer complex was synthesized and found to catalyze the nucleophilic allylation of aldehydes with allyltributyltin. The allylation of a variety of aromatic and aliphatic aldehydes to give the corresponding homoallyl alcohols was performed at room temperature to 60 degrees C in yields ranging from 50% (for typical aliphatic aldehydes) to up to 97% (for aromatic aldehydes) using 5 x 10(-3) to 1 mol % of the Pd catalyst. NMR spectroscopic study indicated that a sigma-allylpalladium intermediate was formed and possibly functions as the nucleophilic species that undergoes addition to the aldehydes.     

5-Amino-4-sulfanylphthalhydrazide as a chemiluminescence derivatization reagent for aromatic aldehydes in liquid chromatography

5-Amino-4-sulfanylphthalhydrazide (ASPH) was synthesized as a chemiluminescence derivatization reagent for aromatic aldehydes in liquid chromatography (LC). Benzaldehyde, 4-tolualdehyde, 4-chlorobenzaldehyde, 4-formylbenzoic acid, 4-hydroxybenzaldehyde and vanillin were used as model compounds to optimize the derivatization conditions. This reagent, ASPH, reacts selectively with aromatic aldehydes in the presence of sodium sulfite and disodium hydrogenphoshite in acidic medium at 100 degrees C to give the corresponding highly chemiluminescent 2-arylbenzothiazole derivatives. The resulting derivatives generated intense chemiluminescence by reaction with hydrogen peroxide and potassium hexacyanoferrate(III) in alkaline solution. The ASPH derivatives of aromatic aldehydes were separated by reversed-phase liquid chromatography with isocratic elution, and detected chemiluminometrically after mixing with oxidizing agents. The detection limits (signal-to-noise ratio = 3) for aromatic aldehydes are in the range 0.2-4.0 fmol for a 20-microl injection volume. Currently, the method is not effective for aliphatic aldehydes because of interfering LC peaks.     

Enantioselective BINOL-phosphoric acid catalyzed Pictet-Spengler reactions of N-benzyltryptamine

Optically active tetrahydro-beta-carbolines were synthesized via an ( R)-BINOL-phosphoric acid-catalyzed asymmetric Pictet-Spengler reaction of N-benzyltryptamine with a series of aromatic and aliphatic aldehydes. The tetrahydro-beta-carbolines were obtained in yields ranging from 77% to 97% and with ee values up to 87%. The triphenylsilyl-substituted BINOL-phosphoric acid proved to be the catalyst of choice for the reaction with aromatic aldehydes. For the aliphatic aldehydes, 3,5-bistrifluoromethylphenyl-substituted BINOL-phosphoric acid was identified as the best catalyst.     

Successful Baylis-Hillman reaction of acrylamide with aromatic aldehydes.

Acrylamide and aromatic aldehydes were found to undergo the Baylis-Hillman reaction at ambient temperature in an aqueous medium in the presence of a stoichiometric amount of base catalyst, DABCO, to give the corresponding 3-hydroxy-2-methylenepropionamides in 61-99% yield. A faster competing, but reversible, non-Baylis-Hillman reaction was initially observed under the conditions to form N-acylhemiaminals, which later disappeared, as the desired Baylis-Hillman adduct was formed as the major product over an extended period of time (12-48 h). This represents the first demonstration of the Baylis-Hillman reaction of aldehydes with acrylamides, which were thought to be inert under atmospheric pressure and at ambient temperature.     

Chromium-catalyzed asymmetric synthesis of 1, 3-diols

An efficient,chromium-catalyzed highly enantioselective preparation of protected 1,3-diols has been achieved.In the presence of a chiral chromium catalyst using the carbazole-based bisoxazoline as the chiral ligand,a variety of optically pure 1,3-diols were synthesized in 34%-87%yields with up to 98%ee.The benzyl as well as silyl ethers were suitable substitutions for the hydroxyl group.Meanwhile,aromatic,aliphatic and α,β-unsaturated aldehydes are well tolerated under the mild reaction conditions.     

Very efficient phosphoramidite ligand for asymmetric iridium-catalyzed allylic alkylation

[reaction: see text] Linear or branched allylic carbonates or acetates undergo enantioselective iridium-catalyzed allylic substitution with sodium malonate. The reaction is wide in scope and affords the branched product in high yield and with high regio- (up to >99:1) and enantioselectivity (up to 98%). Ten aromatic or aliphatic substrates were successfully tested.     

Highly enantioselective cyanosilylation of aldehydes catalyzed by novel beta-amino alcohol-titanium complexes

The beta-amino alcohol 1b-Ti(Oi-Pr)(4) complex has been shown to catalyze the enantioselective cyanosilylation of aldehydes efficiently. In the presence of 5 mol % of 1b-Ti(Oi-Pr)(4) complex catalyst, the aromatic, conjugated, heteroaromatic, and aliphatic aldehydes were converted to their corresponding trimethylsilyl ethers of cyanohydrins in 90-99% yields with up to 94% ee under mild conditions.     

Catalytic enantioselective allylation of aldehydes via a chiral indium(III) complex in ionic liquids

The ionic liquid [hmim][PF₆] has been demonstrated as an efficient and environmentally-friendly reaction medium for the enantioselective allylation of aldehydes via a chiral indium(III) complex. The allylation of a variety of aromatic, α,β-unsaturated and aliphatic aldehydes resulted in moderate to good yields and enantioselectivities (upto 92% ee).     

Zirconium-catalyzed asymmetric Kabachnik–Fields reactions of aromatic and aliphatic aldehydes

An effective catalyst has been developed for the three-component reaction of aldehydes, anilines and phosphites in an asymmetric catalytic Kabachnik–Fields reaction to give α-aminophosphonates. A catalyst was sought that would give high asymmetric inductions for aromatic and, and more particularly, for aliphatic aldehydes since there has not previously been an effective catalyst developed for this class of aldehydes. The optimal catalyst is prepared from three equivalents of the 7,7′-di-t-butylVANOL ligand, one equivalent of N-methylimidazole and one equivalent of zirconium tetraisopropoxide. This catalyst was most efficient in the presence of 10 mol% benzoic acid. Optimal conditions for aryl aldehydes required the use of 3,5-diisopropyl-2-hydroxyaniline and gave the aryl α-aminophosphonates in up to 96% yield and 98% ee over 11 different aryl aldehydes. The best aniline for aliphatic aldehydes was found to be 3-t-butyl-2-hydroxyaniline and gave the corresponding phosphonates in up to 83% yield and 97% ee over 18 examples. The asymmetric inductions for aliphatic aldehydes were comparable with those for aromatic aldehydes with a mean induction of 90% ee for the former and 91% ee for the latter. The best method for the liberation of the free amine from the aniline substituted α-aminophosphonates involved oxidation with N-iodosuccinimide.

An effective catalyst has been developed for the three-component reaction of aldehydes, anilines and phosphites in an asymmetric catalytic Kabachnik–Fields reaction to give α-aminophosphonates.     

Straightforward access to chiral diol bidentate ligands: their efficient enantioselective induction in the addition of diethylzinc to aromatic aldehydes

Enantiopure C₂‐symmetric diol bidentate ligands have been synthesized in a straightforward manner through a three‐step reaction with good yields. The synthesized C₂‐symmetric diol bidentate ligands were used in the addition of diethylzinc to various aromatic aldehydes, a general catalytic benchmark reaction, in order to assess their enantioselective induction properties. The enantioselective addition of diethylzinc to 1‐naphthaldehyde and 3‐chlorobenzaldehyde was achieved with an enantiomeric excess (ee) of up to 98%. All synthesized ligands were also evaluated in the addition of diethyzinc to aromatic aldehydes including an extra metal such as Ti(IV) (up to 99% ee). Copyright © 2014 John Wiley & Sons, Ltd.     

Asymmetric hydrophosphonylation of aldehydes catalyzed by bifunctional chiral Al(III) complexes

A new bifunctional chiral Al(III) complex of BINOL derivative, which contained tert-amine at 3,3′-position of the BINOL, has been developed for the effective enantioselective hydrophosphonylation of aldehydes. A variety of aromatic, heteroaromatic, condensed-ring, α,β-unsaturated, and aliphatic aldehydes were found to be suitable substrates for the reaction, and the desired α-hydroxy phosphonate were obtained in good to excellent yields (up to 99%) with moderate to good enantioselectivities (up to 87% ee) under mild conditions (at 0 °C). A possible catalytic cycle based on the experimental results was proposed.     

New highly asymmetric Henry reaction catalyzed by Cu(II) and a C(1)-symmetric aminopyridine ligand, and its application to the synthesis of miconazole

A new catalytic asymmetric Henry reaction has been developed that uses a C(1)-symmetric chiral aminopyridine ligand derived from camphor and picolylamine. A variety of aromatic, heteroaromatic, aliphatic, and unsaturated aldehydes react with nitromethane and other nitroalkanes in the presence of DIPEA (1.0 equiv), Cu(OAc)(2)*H(2)O (5 mol %), and an aminopyridine ligand (5 mol %) to give the expected products in high yields (up to 99 %), moderate-to-good diastereoselectivites (up to 82:18), and excellent enantioselectivities (up to 98 %). The reaction is air-tolerant and has been used in the synthesis of the antifungal agent miconazole.