Asymmetric aldol reaction using a very simple primary amine catalyst: divergent stereoselectivity by using 2,6-difluorophenyl moiety

Asymmetric aldol reactions of aliphatic ketones or aldehydes with aromatic aldehydes or isatins were catalyzed by a very simple and flexible N-(2,6-difluorophenyl)-l-valinamide. Interestingly, stereochemical course of the reaction of hydroxyacetones or α-branched aliphatic aldehydes as aldol donors was different from that of cycloalkanones.     

Enantioselective butylation of aliphatic aldehydes by mixed chiral lithium amide/n-BuLi dimers

The enantioselective butylation of aliphatic aldehydes with mixtures of n-butyllithium and chiral lithium amides in a diethyl ether–dimethoxymethane solvent mixture is described. Enantiomeric excesses ranging from 91 to 98.5% were observed for several aliphatic alcohols. The asymmetric butylation of the prochiral aldehydes proceeds much faster by the mixed lithium amide/n-BuLi complexes than by tetrameric n-BuLi.     

Aluminum enolates via retroaldol reaction: catalytic tandem aldol-transfer—Tischtschenko reaction of aldehydes with aldol adducts of ketones to ketones

Bidentate aluminum chelates derived from biphenol, binaphthol and catechol were found to be efficient catalysts for aldol-transfer reactions of ketone to ketone aldol adducts with aliphatic or aromatic aldehydes giving rise to the formation of aldol adducts of ketones to the aldehydes. In the presence of an excess of an aliphatic aldehyde, a catalytic tandem aldol-transfer—Tischtschenko reaction is observed. The tandem reaction produces monoesters of 1,3-diols with high anti selectivity and with modest to good chemical yield. 1,2-Unsaturated aldehydes are less reactive in the aldol-transfer reaction and require 2-4 times higher load of the catalyst to be used than aliphatic and aromatic aldehydes. Poor diastereoselectivity was observed in the formation of α-substituted aldols and 2-substituted monoesters of anti-1,3-diols indicating that the aldol-transfer reaction is not diastereoselective with the catalysts studied. The utility of the highly 1,3-anti selective formation of diolmonoesters was found to be limited by acyl migration.     

Erlenmeyer azlactone synthesis with aliphatic aldehydes under solvent-free microwave conditions

2-Phenyl-5(4H)-oxazolone (azlactone) reacts with aliphatic aldehydes upon adsorption on neutral alumina and irradiation with microwaves (<2 min). The corresponding condensation products are obtained in good yields (62-78%), indicating the satisfactory resolution of a long-standing problem plaguing the classical Erlenmeyer synthesis (poor results with aliphatic aldehydes). Plausible mechanistic reasons for the success of the procedure are discussed.     

Synthesis of gem-difluorides from aldehydes using DFMBA

Synthesis of gem-difluorides from aldehydes was effectively achieved using DFMBA and Et₃N-3HF under microwave irradiation or conventional thermal heating. Both aromatic and aliphatic aldehydes could be converted to the corresponding gem-difluorides in good yields.     

Supramolecular interaction controlled and calix[4]arene ligand assisted Pd-catalyzed C(sp3)−H arylation of aliphatic aldehydes

A calix[4]arene ligand assisted direct β-C?H arylation of tertiary aliphatic aldehydes has been developed via a Pd-catalyzed C(sp³)?H functionalization process. This strategy exhibited good functional group compatibility and C?H bond site-selectivity. Mechanism studies have shown that both synergistic effect and cationic-π supramolecular interaction between calixarene cavity and transition-metal catalytic center may play an important role in this catalytic cycle. This complementary method would be used in organic and medical chemistry due to the importance of tertiary aliphatic aldehydes.     

Proline-catalyzed asymmetric aldol reactions of tetrahydro-4H-thiopyran-4-one with aldehydes

Proline-catalyzed enantioselective direct intermolecular aldol reactions of tetrahydro-4H-thiopyran-4-one with various aldehydes give anti adducts with high diastereo- and enantioselectivities in moderate to excellent yields. With the aromatic aldehydes best results were obtained in wet DMF whereas dry DMSO generally was superior with the aliphatic aldehydes. Desulfurization of the adducts with Raney Ni provides products equivalent to aldols from 3-pentanone with potential applications in polypropionate synthesis.     

PmHNL catalyzed synthesis of (R)-cyanohydrins derived from aliphatic aldehydes

Hydroxynitrile lyase from the Japanese apricot (Prunus mume) catalyzes the formation of several aliphatic cyanohydrins in an asymmetric fashion. By employing a biphasic reaction system, aliphatic aldehydes with various structural features can be converted to the corresponding (R)-cyanohydrins with good overall yield and enantiomeric excess.     

Preparation of TMS protected trifluoromethylated alcohols using trimethylamine N-oxide and trifluoromethyltrimethylsilane (TMSCF3)

A catalytic trifluoromethylation of aldehydes using trimethylamine N-oxide and trifluoromethyltrimethylsilane (TMSCF₃) is described. Aromatic, aliphatic and α,β-unsaturated aldehydes provided good to excellent yields of the corresponding trifluoromethylated products.     

Iron-catalyzed sulfonylimine synthesis under neutral conditions

A convenient FeCl₃-catalyzed synthesis of N-sulfonylimines via the condensation of aldehydes with N-sulfonylamides in mild and neutral conditions (in ethanol at room temperature) is reported. This procedure constitutes the first iron-catalyzed synthesis of N-sulfonylimines and is adapted to the condensation of both aromatic and aliphatic aldehydes.     

Application of biphasic reaction procedure using ferric chloride dissolved in an imidazolium salt and benzotrifluoride (FeIm-BTF procedure) to aza-Prins cyclization reaction

Aza-Prins cyclization reaction of N-tosyl-3-butenylamine with aliphatic and aromatic aldehydes was performed using a combination of FeCl₃ and 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF₆) or 1-butyl-3-methylimidazolium tetrachloroferrate (BmimFeCl₄) in benzotrifluoride (BTF). The desired N-tosyl-4-chloro-2-substituted piperidines were obtained from aliphatic aldehydes in comparable yields to those for the previously reported reactions in which FeCl₃ was used in CH₂Cl₂. On the other hand, significant progress for the piperidine synthesis from aromatic aldehydes has been achieved, particularly when BmimFeCl₄ was used with FeCl₃ in BTF.     

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.     

Synthesis of (−)-(5R,6S)-6-acetoxyhexadecanolide based on l-proline-catalyzed asymmetric aldol reactions

A convenient method for proline-catalyzed asymmetric aldol reactions using synthons of straight-chain aliphatic aldehydes, and aldehydes bearing a 1,3-dithiane moiety at the β-position, has been developed. This method was successfully applied to the synthesis of (−)-(5R,6S)-6-acetoxyhexadecanolide, an oviposition attractant pheromone of the female Culex mosquito.     

Intramolecular-Prins-cyclization: a novel synthesis of hexahydro-2H-furo[3,2-c]pyran derivatives

p-Toluenesulfonic acid is found to catalyze the coupling of (Z)-hex-3-ene-1,6-diol with a series of aldehydes by means of intramolecular-Prins-cyclization to provide the corresponding hexahydro-2H-furo[3,2-c]pyran derivatives in good yields with complete cis-selectivity, whereas the coupling of (E)-hex-3-ene-1,6-diol with aliphatic aldehydes gave trans-fused bicyclic furopyrans.     

Molecular iodine: An efficient and environment-friendly catalyst for the synthesis of calix[4]resorcinarenes

Iodine catalyzes the cyclocondensation of various aldehydes with resorcinol to give tetrameric cyclic products, resorcinarenes. Through the reaction of resorcinol with aromatic aldehydes, the product is obtained as a mixture of two isomers, the all-cis isomer (rccc) and the cis-trans-trans isomer (rctt), whereas a single diastereomer, the all-cis, is formed with aliphatic aldehydes. Besides excellent isolated yields, the use of iodine makes this procedure simple, convenient, cost-effective and practical.     

Stereoselective Wittig olefination reactions employing a novel ortho-P-aryl alkoxide effect

Non-stabilized ortho-P-alkoxy-substituted ylides react with aromatic and aliphatic aldehydes providing (E)-olefins with high stereocontrol, also allowing easy phosphine oxide removal in certain cases.     

Self-assembly of organocatalysts for the enantioselective Michael addition of aldehydes to nitroalkenes

A proline–thiourea self-assembled organocatalyst is described as a good catalyst for the enantioselective nitro-Michael addition of aldehydes to nitroalkenes. The reaction is efficient with 5% of the thiourea, to give moderate to good enantioselectivity (up to 76% ee). High syn-selectivity was obtained with both branched and unbranched aliphatic aldehydes. This is the first example of self-assembly of organocatalysts with an achiral additive in a Michael addition wherein aldehydes are utilized as donors.     

A highly enantio- and diastereoselective 1,3-dimethylallylation of aldehydes

A highly enantio- and diastereoselective pentenylation of aldehydes is described. The homoallylic alcohol derived from 1,3-dimethylallylation of (-)-menthone undergoes an efficient allyl-transfer reaction with a wide range of aliphatic aldehydes in the presence of an acid catalyst to give rise to the corresponding 4-methyl-2(E)-penten-4-yl-5-ol products in good yields with high enantio- and 4,5-syn-selectivities.     

A simple method for the oxidation of primary alcohols with o-iodoxybenzoic acid (IBX) in the presence of acetic acid

A simple method for the oxidation of primary alcohols to aldehydes using o-iodoxybenzoic acid (IBX) with the addition of stoichiometric acetic acid has been developed. Addition of acetic acid significantly accelerated the reaction rate. Under these conditions, primary aliphatic, benzylic, and allylic alcohols are smoothly converted to aldehydes in high yields (90-97%).     

A new Yb-catalyzed pinacol and imine-coupling reaction

Ytterbium triflate, Yb(OTf)₃, catalyzes the intermolecular reductive homocouplings of imines, aldehydes, and ketones at loadings of 5 mol % in the presence of Mg and Me₃SiCl to give isolated yields of up to 95%. Diastereoselectivity of up to 4/96 (dl/meso) is achieved for aromatic aldehydes, up to 100% dl for aliphatic aldehydes, and 100% dl for an intramolecular imine coupling.