Chiral macrocycle-catalyzed highly enantioselective phenylacetylene addition to aliphatic and vinyl aldehydes

The 1,1'-binaphthyl macrocycle (S)-2 is found to be an excellent catalyst for the alkyne addition to aldehydes. In the presence of (S)-2 (20 mol %) and Me2Zn (2 equiv) in THF at room temperature, the addition of phenylacetylene to linear or branched aliphatic aldehydes and vinyl aldehydes gave various propargylic alcohols with 89-96% ee.     

Highly enantioselective addition of dimethylzinc to arylaldehydes catalyzed by (2S)-1-ferrocenyl-methylaziridin-2-yl(diphenyl)methanol

Asymmetric addition of dimethylzinc to a wide variety of aromatic aldehydes is described in the presence of a catalytic amount of chiral β-amino alcohol [(2S)-1-ferrocenyl- methylaziridin-2-yl(diphenyl)methanol], and a reaction enantioselectivity of up to 97.5% ee was achieved in this transformation in the absence of additional metals such as Ti or Ni. The results showed that this particular addition reaction, characterized by the lower reactivity of dimethylzinc with aldehydes, was more sensitive to structural variations in substrate aldehydes than the corresponding diethylzinc addition. A possible transition state for the catalytic asymmetric addition has been proposed on the basis of previous studies.     

酒石酸衍生物促进的醛酮不对称烷基加成反应研究进展

酒石酸分子具有含两个手性碳原子的对称结构, 且价廉易得. 因此, 酒石酸及其衍生物在不对称合成领域被广泛应用, 其中α,α,α’,α’-四苯基-2,2-二甲基-1,3-二氧环戊烷-4,5-二甲醇(简称TADDOL)及其类似物、手性酰氧硼烷(简称CAB)等促进的不对称催化反应研究得更为深入和细致. 综述了近年来TADDOL和CAB等作为手性配体在二乙基锌试剂与醛酮、烯丙基有机金属试剂以及烷基铈试剂与醛的加成反应中的应用, 同时简要地介绍了各手性配体的催化效果.     

Asymmetric multicomponent domino reactions and highly enantioselective conjugated addition of thiols to alpha,beta-unsaturated aldehydes

An organocatalytic asymmetric multicomponent domino and a conjugated addition reaction to alpha,beta-unsaturated aldehydes are presented. The development is based, first, on an organocatalyzed highly enantioselective nucleophilic thiol addition to the beta-carbon atom in the iminium ion intermediate, followed by an electrophilic amination of the alpha-carbon atom to the enamine intermediate. The multicomponent reactions proceed to give enantiopure amino-thiols in moderate to good yields. Furthermore, the organocatalyzed thiol addition to alpha,beta-unsaturated aldehydes takes place in good yields and excellent enantioselectivities.     

Two tandem sequential reactions catalyzed by [Au], N-heterocyclic carbenes (NHC) and organic bases

Herein we describe two coupling reactions of aldehydes and activated alkynes to give chalcones or alkenyl esters depending on the base used. Chalcones were obtained by activation of alkynes by Au^I and of aldehydes by NHC in presence of triethylamine. Alkenyl esters were obtained via generation of gold nanoparticles, aerial oxidation of aldehydes to carboxylates and their subsequent nucleophilic addition to the alkyne functionality.     

Asymmetric diethylzinc addition and phenyl transfer to aldehydes using chiral cis-cyclopropane-based amino alcohols

A new series of amino alcohols with a chiral cyclopropane backbone have been developed and used in the catalytic asymmetric diethylzinc addition and phenyl transfer to various types of aldehydes. These cyclopropane-based chiral amino alcohols show high enantioselectivity in the addition of organozincs to aromatic and aliphatic aldehydes. For diethylzinc addition to aromatic and aliphatic aldehydes, up to 97% ee and 93% ee are obtained, respectively. For the phenyl transfer to aromatic aldehydes, the best enantioselectivity was 89% ee.     

BiBr3-initiated tandem addition/silyl-Prins reactions to 2,6-disubstituted dihydropyrans

A tandem addition/silyl-Prins reaction efficiently affords cis-2,6-disubstituted dihydropyrans (DHPs) using 5 mol % of BiBr3 in CH2Cl2. The reaction occurs between delta-triethylsilyloxyvinyltrimethylsilanes and a variety of aldehydes to give good to excellent isolated yields of DHPs. The diastereoselectivities in the crude products are significantly affected by aldehyde substitution with electron-rich aldehydes, providing 2-3:1 (cis:trans) and neutral (or electron-poor) aldehydes affording dr > or = 19:1 (cis:trans).     

Cyanide ion cocatalysis in Ti(salen) catalysed asymmetric cyanohydrin carbonate synthesis

In the presence of potassium cyanide or the potassium cyanide/18-crown-6 complex as a cocatalyst, 1-2 mol% of titanium(salen) complex catalyses the asymmetric addition of achiral cyanoformates to aldehydes, giving cyanohydrin carbonates with high enantiomeric excesses; and catalyses the diastereoselective addition of chiral cyanoformates derived from alpha-methylbenzyl alcohol to aldehydes, a reaction which exhibits double asymmetric induction.     

Reaction of N-vinylic phosphazenes with alpha,beta-unsaturated aldehydes. Azatriene-mediated synthesis of dihydropyridines and pyridines derived from beta-amino acids

Aza-Wittig reaction of N-vinylic phosphazenes (1,2 addition), derived from diphenylmethylphosphine or derived from trimethylphosphine with alpha,beta-unsaturated aldehydes, leads to the formation of 3-azatrienes through a [2 + 2]-cycloaddition-cycloreversion sequence. The presence of an alkyl substituent in position 3 of N-vinylic phosphazenes increases the steric interactions, and [4 + 2] periselectivity (1,4 addition) is observed. Reaction of azatrienes with alpha,beta-unsaturated aldehydes yields pyridines.     

Direct enantioselective Michael addition of aldehydes to vinyl ketones catalyzed by chiral amines

Chiral amines such as (S)-2-[bis(3,5-dimethylphenyl)methyl]pyrrolidine and the C(2)-symmetric (2S,5S)-2,5-diphenylpyrrolidine can catalyze the direct enantioselective Michael addition of simple aldehydes to vinyl ketones. The conditions for this organocatalytic reaction have been optimized and it has been found that the chiral amines catalyze the formation of optically active substituted 5-keto aldehydes in good yields and enantioselectivities, using aldehydes and, e.g., methyl vinyl ketone as starting compounds. Taking into account that the chiral amine can activate the aldehyde and/or the enone, the mechanism for the reaction has been investigated. On the basis of intermediate synthesis, nonlinear effect, and theoretical investigations, the mechanism for the catalytic direct enantioselective Michael addition of aldehydes to vinyl ketones is discussed.     

One-pot enol silane formation-Mukaiyama aldol reactions: Crossed aldehyde-aldehyde coupling,thioester substrates,and reactions in ester solvents

Trimethylsilyl trifluoromethanesulfonate (TMSOTf) and a trialkylamine base promote both in situ enol silane/silyl ketene acetal formation and Mukaiyama aldol addition reactions between a variety of reaction partners in a single reaction flask. Isolation of the required enol silane or silyl ketene acetal is not necessary. For example, crossed aldol reactions between α-disubstituted aldehydes and non-enolizable aldehydes yield β-hydroxy aldehydes in good yield. In a related reaction, the common laboratory solvent ethyl acetate functions as both an enolate precursor and a green reaction solvent. When thioesters are employed as enolate precursors, high yields for additions to non-enolizable aldehydes are routinely observed.     

Furanoside phosphite-phosphoroamidite: new ligand class for the asymmetric nickel-catalyzed trialkylaluminium addition to aldehydes

We have described the first successful application of bidentate ligands in the asymmetric Ni-catalyzed trialkylaluminium addition to several aldehydes. The ligands are prepared from inexpensive d-(+)-xylose and d-(+)-glucose and have the advantage of carbohydrate and phosphite/phosphoroamidite moieties. After systematic variation of the position of the phosphoroamidite group at either C5 or C-3, the configuration of C-3 and the substituents in the biaryl phosphite/phosphoroamidite moieties, enantioselectivities up to 84% and high yields were obtained in the Ni-catalyzed trialkylaluminium addition to several aldehydes.     

The use of bifunctional catalyst systems in the asymmetric addition of alkynylzinc to aldehydes

The bifunctional ligand 2a showed a more enhanced reactivity than that of the corresponding amino alcohol ligand in the asymmetric addition of alkynylzinc to benzaldehyde. The bifunctional ligand 2a can catalyze the addition of phenylacetylene to various types of aldehydes including aromatic aldehydes, aliphatic aldehydes, and α,β-unsaturated aldehydes with high enantioselectivity (81–98% ee). The conditions of this catalytic process are both mild and simple.     

Intermolecular Cross-Acyloin Reactions by Fluoride-Promoted Additions of O-Silyl Thiazolium Carbinols

The addition of acyl anion equivalents to aliphatic aldehydes (crossed-acyloin reaction) has been developed. Cesium fluoride with isopropanol as solvent promotes the addition of O-silyl thiazolium carbinols to various aliphatic aldehydes in moderate to good yields. These reactions represent a general procedure for the selective coupling of aliphatic aldehydes by an acyl anion reaction which have been problematic until now.     

Novel functionalized trisubstituted allylboronates via Hosomi-Miyaura borylation of functionalized allyl acetates

[reaction: see text] A series of novel functionalized achiral and chiral allylboronates have been synthesized via the nucleophilic addition of boronates on allyl acetates derived via vinylalumination or Baylis-Hillman reaction of aldehydes. These reagents, upon allylboration with aldehydes, furnish beta-substituted-alpha-methylene-gamma-butyrolactones stereoselectively.     

Reduction of Aromatic Aldehydes,Ketones with Acyloxy Substituent at the Ortho-position by NaBH4 in the Presence of Waters

n unusual reduction of some aromatic aldehydes, ketones by sodium borohydride was discovered. In a THF/H₂O or DMSO/H₂O solvent system the aromatic aldehydes, ketones with acyloxy substituent on the ortho-position to the carbonyl group can be reduced to the corresponding alkyl phenols. This unusual reduction is applicable also to the corresponding alcohols of all the above aldehydes, ketones. A putative mechanism was suggested. In addition to the above aldehydes, ketones, benzyl alcohols, certain 4-acyloxybenzyl esters(probably also the 2-substituted analogues) such as 4-benzoyloxybenzyl benzoate was also found to be reduced to methylphenol by this unusual reduction.     

A novel synthesis of 1,2,4-oxadiazoles and isoxazoles

A novel synthesis of 1,2,4-oxadiazoles and isoxazoles is described by utilizing the reactions between amidoximes and α,β-alkynic aldehydes and/or ketones. Conjugate addition products, obtained from amidoximes and α,β-alkynic aldehydes and/or ketones, afford 1,2,4-oxadiazoles and isoxazoles when treated with bases and acids, respectively. 1,2,4-Oxadiazoles can also be synthesized directly from amidoximes and α,β-alkynic aldehydes in a one-pot manner under basic conditions. The reactions are general for a variety of starting compounds and tolerate the presence of aryl, heteroaryl and alkyl groups.     

Stereoselective aldol additions of achiral ethyl ketone-derived trichlorosilyl enolates

Methods for the preparation of geometrically defined enoxy(trichlorosilanes) derived from ethyl ketone enolates have been developed. The addition of enoxy(trichlorosilanes) (trichlorosilyl enolates) to aldehydes proceeds with good yields in the presence of catalytic amounts of chiral phosphoramides. The reaction of Z-trichlorosilyl enolates to aryl aldehydes affords aldol products with good to excellent diastereo- and enantioselectivities. Phosphoramide-catalyzed aldol additions lacked substrate generality providing modest selectivities with unsaturated and aliphatic aldehydes. In all cases, the phosphoramide-catalyzed aldol addition of E-trichlorosilyl enolates to aldehydes provided good yields with moderate to good stereoselectivities.     

Titanium fluoride complexes as catalysts for the enantioselective addition of Me3Al to aldehydes

We report a Ti(IV) catalyst prepared in situ from TiF₄ for the asymmetric addition of trimethylaluminum to aldehydes. The process we detail herein does not necessitate the use of excess trimethylaluminum or Ti(IV) reagent. Good enantioselectivities are achieved with a variety of aromatic and heteroaromatic aldehydes with the products isolated in high yield.     

Highly stereoselective three-component reactions of phenylselenomagnesium bromide,acetylenic sulfones,and saturated aldehydes/ketones or alpha,beta-unsaturated enals or enones

beta-Phenylseleno-alpha-tolylsulfonyl-substituted alkenes were synthesized via the three-component conjugate-nucleophilic addition of acetylenic sulfones, phenylselenomagnesium bromide, and carbonyl compounds, such as aldehydes, aliphatic ketones, or alpha,beta-unsaturated enals or enones. The reaction is highly regio- and stereoselective with moderate to good yields. Functionalized allylic alcohols were obtained in the case of aldehydes and aliphatic ketones. In the case of alpha,beta-unsaturated enones, functionalized allylic alcohols or functionalized gamma,delta-unsaturated ketones were obtained, depending on the structures of the ketones.