Allyltrichlorostannane additions to chiral aldehydes

Chiral and achiral allyltrichlorostannanes reacted with chiral β-alkoxy and syn and anti α-methyl-β-alkoxy aldehydes to give the corresponding homoallylic alcohols with moderate to high diastereoselectivities.     

Chiral ferrocenyl amino alcohols for enantioselective additions of diethylzinc to aldehydes

Optically active ferrocenyl amino alcohols have been prepared from commercially available l-alaninol, l-leucinol and l-valinol. They have been utilized as chiral ligands in the catalytic addition of diethylzinc to aldehydes. The influence of the substituents on the stereogenic centers of the ligand has been studied. Enantioselectivities up to 95% have been obtained.     

Amino thiols versus amino alcohols in the asymmetric alkynylzinc addition to aldehydes

A series of modular amino thiol and amino alcohol ligands have been synthesized in enantiopure form from common enantiopure precursors. Their structures have been optimized for performance in the asymmetric alkynylzinc addition to aldehydes, and a direct comparison of the effect of the S and O coordinating atoms on the catalytic outcome of these ligands has been performed. Amino thiols have shown to be superior as ligands for this type of chemistry.     

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.     

Chiral boron enolate aldol additions to chiral aldehydes

We have examined the double-diastereodifferentiating aldol addition reactions of chiral enolborinate 1a with chiral aldehydes leading to the corresponding aldol adducts with excellent levels of 1,5-anti diastereoselection.     

Direct asymmetric aldol reaction of aryl ketones with aryl aldehydes catalyzed by chiral BINOL-derived zincate catalyst

Direct asymmetric aldol reaction of aryl ketones with aryl aldehydes catalyzed by chiral metal complex is reported for the first time herein. Two novel semicrown chiral ligands 1a and 1b were synthesized from (S)- and (R)-BINOL, respectively, and then employed to catalyze the direct asymmetric aldol addition of aryl ketones to aryl aldehydes. Introduced with 2.0 equiv of diethylzinc, 1b had higher enantioselectivity than 1a. Up to 97% yield and up to 80% enantioselectivity were achieved.     

Diastereoselective additions of chiral vinylzinc reagents to alpha-chiral aldehydes

[reaction: see text] Additions of vinylic zinc bromide reagents to alpha-chiral aldehydes (R(1) = CH(2)OTBS, R(2) = Me; R(1) = Me, R(2) = OTBS) in the presence of lithiated (+)- or (-)-N-methylephedrine proceed with predominant reagent control to afford anti or syn adducts stereoselectively, except when the aldehydes possess an alkoxy substituent at the alpha- or beta-positions (R(1) = Me, R(2) = OBn; R(1) = CH(2)OBn, R(2) = Me), in which case chelation-controlled adducts predominate.     

Limonene oxide derived aziridinyl alcohols as highly efficient catalysts for asymmetric additions of organozinc species to aldehydes

The facile synthesis of a series of novel catalysts bearing a tertiary hydroxyl group and an aziridine moiety as chelating centers constructed on the scaffold derived from limonene oxide is described. The newly prepared compounds have been tested for the enantioselective addition of diethylzinc and phenylethynylzinc to aryl and alkyl aldehydes, affording the corresponding chiral alcohols in very high chemical yields (up to 96%) and with excellent ee’s of ca. 95%.     

手性氨基醇在不对称催化中的应用及新进展

综述了手性氨基醇作为配体或催化剂在不对称合成中的应用及最新进展。     

Synthesis of chiral ferrocenyl aziridino alcohols and use in the catalytic asymmetric addition of diethylzinc to aldehydes

A series of novel chiral ferrocenyl aziridino alcohols 5a–i were conveniently synthesized from L-serine and ferrocenecarboxaldehyde. These compounds have been used as chiral catalysts in the asymmetric addition of diethylzinc to aldehydes and the effects of the ligand structures on the enantioselectivity was studied. Enantioselectivities up to 98.8% have been obtained.     

Organocatalyzed asymmetric α-hydroxyamination of α-branched aldehydes: asymmetric synthesis of optically active N-protected α,α-disubstituted amino aldehydes and amino alcohols

Enantioselective direct α-hydroxyamination and α-aminoxylation of α-branched aldehydes using a proline-derived tetrazole catalyst is described herein. α-Hydroxyamination adducts with up to 90% ee were obtained by the reaction of nitrosobenzene with unactivated α-branched aldehydes under mild reaction conditions.     

Lactic acid derived aziridinyl alcohols as highly effective catalysts for asymmetric additions of an organozinc species to aldehydes

A straightforward synthetic route to a series of new catalysts bearing secondary hydroxyl and aziridine moieties as nucleophilic centers built on the chiral skeleton of (S)-(+)-lactic acid is described. All of the new compounds have been tested in the enantioselective addition of diethyl- and phenylethynylzinc to aryl and alkyl aldehydes, yielding the corresponding chiral alcohols in high chemical yields (up to 85%) and good ee’s of approximately 85%. The influence of the stereogenic center located at the aziridine subunit on the stereochemical outcome is also discussed.     

Sterically encumbered chiral amino alcohols for titanium-catalyzed asymmetric intramolecular hydroamination of aminoallenes

A variety of sterically encumbered amino alcohol ligands were prepared in a two-step modular synthesis. The titanium complexes of these ligands were prepared in situ and used as catalysts for hydroamination. The intramolecular hydroamination of 6-methyl-hepta-4,5-dienylamine at 135 °C with 5 mol % catalyst gave exclusively 2-(2-methyl-propenyl)-pyrrolidine with enantiomeric excesses up to 16%.     

Diamine-catalyzed asymmetric Michael additions of aldehydes and ketones to nitrostyrene

[reaction: see text] The direct Michael addition of aldehydes and ketones to nitrostyrene, catalyzed by N-i-Pr-2,2'-bipyrrolidine, is described. The desired 1,4-adducts are obtained in excellent yield with enantioselectivities up to 85% ee and dr up to 95:5 of the syn product.     

Direct asymmetric iodination of aldehydes using an axially chiral bifunctional amino alcohol catalyst

A direct asymmetric iodination reaction of aldehydes with NIS was found to be catalyzed by the novel axially chiral bifunctional amino alcohol (S)-1d. This method represents the rare example of the catalytic and highly enantioselective synthesis of optically active alpha-iodoaldehydes.     

Catalyzed asymmetric aryl transfer reactions to aldehydes with boronic acids as aryl source

Chiral diaryl methanols are important intermediates for the synthesis of biologically active compounds. Here, we describe a flexible method for their catalyzed asymmetric synthesis from readily available starting materials. Noteworthy is the fact that with a single catalyst both enantiomers of the product are accessible simply by choosing the appropriate combination of aryl boronic acid or aldehyde as aryl donor and acceptor, respectively. The catalysis with a planar-chiral ferrocene is easy to perform and yields a broad range of products with excellent enantioselectivities (up to 98% ee).     

Efficient asymmetric addition of diethylzinc to aldehydes using C2‐novel chiral pyridine β‐amino alcohols as chiral ligands

A series of novel C₂‐symmetric chiral pyridine β‐amino alcohol ligands have been synthesized from 2,6‐pyridine dicarboxaldehyde, m‐phthalaldehyde and chiral β‐amino alcohols through a two‐step reaction. All their structures were characterized by ¹H NMR, ¹³C NMR and IR. Their enantioselective induction behaviors were examined under different conditions such as the structure of the ligands, reaction temperature, solvent, reaction time and catalytic amount. The results show that the corresponding chiral secondary alcohols can be obtained with high yields and moderate to good enantiomeric excess. The best result, up to 89% ee, was obtained when the ligand 3c (2S,2′R)‐2,2′‐((pyridine‐2,6‐diylbis(methylene))bisazanediyl))bis(4‐methyl‐1,1‐diphenylpentan‐1‐ol) was used in toluene at room temperature. The ligand 3g (2S,2′R)‐2,2′‐((1,3‐phenylenebis(methylene))bis(azanediyl))bis(4‐methyl‐1,1‐diphenylpentan‐1‐ol) was prepared in which the pyridine ring was replaced by the benzene ring compared to 3c in order to illustrate the unique role of the N atom in the pyridine ring in the inductive reaction. The results indicate that the coordination of the N atom of the pyridine ring is essential in the asymmetric induction reaction. Copyright © 2014 John Wiley & Sons, Ltd.     

Sterically encumbered chiral amino alcohols for the titanium catalyzed asymmetric alkylation of benzaldehyde

Sterically encumbered chiral l-amino alcohols with secondary amines and tertiary alcohols catalyze the enantioselective alkylation of benzaldehyde with diethyl zinc. Using 2 mol % of amino alcohol catalyst predominantly gave (R)-1-phenylpropanol with enantiomeric excesses of up to 61%. Using the in situ prepared titanium complex at 2 mol % as catalyst also favored the (R)-enantiomer with enantiomeric excesses of up to 73%. In almost all cases, the addition catalyzed by the titanium complex exhibited higher enantioselectivity than that of the amino alcohol ligand alone.