An efficient synthesis of pyrimidines from beta-amino alcohols

[reaction: see text] Pyrimidinones 3 were chemoselectively reduced by using metal-catalyzed hydrogenation and stereoselectively substituted by various nucleophiles. Starting from beta-amino alcohols 1, the overall process allows efficient access to substituted pyrimidines 4 and 6.     

An efficient synthesis of isocarbacyclin starting from furfural

Two synthetic routes to isocarbacyclin starting from furfural are described. One route involves the regioselective hydrogenation of the disubstituted olefin in the presence of two other olefinic double bonds, and the other includes the highly regioselective organocopper coupling with the allylic etectrophile as a key step.     

Highly enantioselective synthesis of beta-amino alcohols

[reaction: see text] N,N-Dialkyl-beta-amino alcohols derived from alpha-amino acids can be rearranged enantiospecifically by using TFAA/Et3N/NaOH to give 1,2-amino alcohols with enantiomeric excess up to 99%.     

Dynamic kinetic resolution of beta-azido alcohols. An efficient route to chiral aziridines and beta-amino alcohols

Enzymatic resolution of beta-azido alcohols in combination with ruthenium-catalyzed alcohol isomerization led to a successful dynamic kinetic resolution. A variety of racemic beta-azido alcohols were efficiently transformed to the corresponding enantiomerically pure acetates (ee up to 99% and conversion up to 98%). The synthetic utility of this procedure has been illustrated by the practical synthesis of (S)-propanolol I and (R)-beta-azido-alpha-(4-methoxyphenyl)ethanol ((R)-1c), a direct precursor of denopamine II.     

Highly enantioselective synthesis of beta-amino alcohols: a catalytic version

Highly enantioselective rearrangement of beta-amino alcohols was realized by using a catalytic amount of trifluoroacetic anhydride.     

An efficient synthesis of the natural tetrahydrofuran pachastrissamine starting from D-ribo-phytosphingosine

[reaction: see text] The natural product pachastrissamine, an anhydrophytosphingosine derivative isolated from various sponges and endowed with cytotoxic activity against several human carcinoma cell lines, was synthesized in three steps and with 72% overall yield from d-ribo-phytosphingosine.     

Chemistry of N-Boc-N-tert-butylthiomethyl-protected alpha-aminoorganostannanes: diastereoselective synthesis of primary beta-amino alcohols from alpha-aminoorganostannanes

Reaction of N-Boc-N-tert-butylthiomethyl-protected alpha-aminoorganostannanes with n-BuLi generates the corresponding alpha-aminoorganolithiums. Reactions of these organolithiums with aromatic aldehydes provides N-protected beta-amino alcohols with diastereoselectivities up to >99:1 anti/syn; with aliphatic aldehydes, diastereoselectivities were typically 1:1. Diastereoselectivities varied depending on the amount of aldehyde used. The N-protected beta-amino alcohols could be deprotected to primary amines by treatment with NaH to generate oxazolidinones followed by basic hydrolysis. Alternatively, treatment of the protected amino alcohols with acid furnished cyclic acetals that could be deprotected to primary amines with BF(3).OEt(2) and HS(CH(2))(3)SH. Transmetalation of enantiomerically enriched organostannanes with n-BuLi at -95 degrees C provided organolithiums that, although less configurationally stable than N-Boc-N-methyl-protected alpha-aminoorganolithiums, could be trapped with aldehydes with near-complete retention of configuration.     

Lewis acid promoted highly stereoselective rearrangement of 2,3-aziridino alcohols: a new efficient approach to beta-amino carbonyl compounds

A new Lewis acid promoted rearrangement reaction of 2,3-aziridino alcohols was discovered, which involved the highly stereoselective construction of a diastereogenic quaternary carbon center and efficient formation of beta-amino carbonyl compounds in excellent yields. A wide variety of Lewis acids were proved to be effective for the reaction, and a possible reaction mechanism was also discussed.     

An efficient synthesis of dihydrofuranyl spirooxindoles from isatin-derived propargylic alcohols and 1,3-dicarbonyls

Various dihydrofuranyl spirooxindoles have been synthesized via montmorillonite K-10-catalyzed propargylation of 1,3-dicarbonyl compounds with isatin-derived propargylic alcohols and subsequent base-mediated 5-exo-dig cyclization.     

An efficient regioselective synthesis of endocrocin and structural related natural anthraquinones starting from emodin

Endocrocin and related naturally occurring anthraquinone pigments like cinnalutein could be synthesized regioselectively via a Marschalk type reaction, starting from the natural hydroxy anthraquinone emodin. Furthermore, the new tri-O-methyl protected emodin-2-carbaldehyde may serve as a promising synthon for new bathochromically shifted, higher generation photodynamically active hypericin derivatives.     

Copper-catalyzed arylation of beta-amino alcohols

[reaction: see text] Methods for synthesizing N-aryl beta-amino alcohols and O-aryl beta-amino alcohols are described. The presence of a neighboring hydroxyl or amino group, respectively, is thought to activate beta-amino alcohols toward these transformations. These protocols significantly increase access to a variety of arylated beta-amino alcohols.     

Diastereoselective aldolization of alpha-aminonitriles. Diastereoselective synthesis of beta-amino alcohols and beta,gamma-diamino alcohols

Aldolization performed by addition of lithiated N-benzyl-N-tert-butylaminoacetonitrile to aldehydes provides diastereomerically pure anti-beta-hydroxy-alpha-aminonitriles. They are transformed into syn,anti-protected beta,gamma-diamino alcohols by a two-step procedure, involving addition of a Grignard reagent and reduction. The cleavage of the N-tert-butyl group is achieved by a simple acidic treatment. The application of this methodology to chiral, nonracemic aldehydes is studied. Starting from D-isopropylideneglyceraldehyde, an anti, anti, syn, anti-(2R,3S,4S,5R,6R)-diaminotriol is prepared in acceptable yield and with a good level of diastereoselectivity.     

A mild and efficient synthesis of thiolesters from alcohols

Numerous functionally diverse thiolesters are prepared in high yield in a mild “one-pot” synthesis from activated alcohols and thiolacids under Lewis acid catalysis.     

Reduction of 2,3-dihydroisoxazoles to beta-amino ketones and beta-amino alcohols

[chemical reaction: see text]. We report the reduction of 2,3-dihydroisoxazoles to beta-amino ketones and beta-amino alcohols. The latter are obtained in high diastereoselectivity with preference for the syn isomer.     

Silver-catalyzed efficient synthesis of enaminones from propargyl alcohols and amines

Enaminones are used as the key intermediates to construct heterocyclic compounds with various bioactivities. In this study, a simple and efficient approach for the synthesis of enaminones via amination of propargyl alcohols was developed. Under the catalysis of Ag₂CO₃, the reaction proceeded smoothly to afford the desired products in good yields. Preliminary mechanism experiments showed that Ag₂CO₃ played an essential role in the procedure of the reaction.     

Biginelli reaction starting directly from alcohols

An efficient of one-pot oxidative access to 3,4-dihydropyrimidin-2-(1H)-ones directly from aromatic alcohols under mild conditions is reported. The protocol involves 1-methylimidazolium hydrogen sulphate [Hmim]HSO₄ catalyzed oxidation of aromatic alcohols to aromatic aldehydes with NaNO₃ followed by their cyclocondensation with 1,3-dicarbonyl compounds and urea in the same reaction vessel at 80 °C within 2-4 h to afford 3,4-dihydropyrimidin-2-(1H)-ones in 55-97% overall yields. Thus, the present work utilizing alcohols instead of aldehyde in Biginelli reaction is a valid and green alternative to the classical synthesis of 3,4-dihydropyrimidin-2-(1H)-ones.     

A new synthesis of sultams from amino alcohols

The base-mediated cyclization of N,O-dimesylate derivatives of cyclic and acyclic amino alcohols provides a simple access to five- and six-member sultams: isothiazolidine-1,1-dioxides and thiazinane-1,1-dioxides respectively.     

Stereoselective synthesis of 1,2-disubstituted beta-amino alcohols by nucleophilic addition to N-tert-butanesulfinyl alpha-alkoxyaldimines

N-tert-Butanesulfinyl alpha-alkoxyaldimines are readily prepared from protected (S)-lactals without epimerization at the alpha-stereocenter. Addition of ethyl and phenyl Grignard reagents, as well as the titanium enolate of methyl acetate, to the N-tert-butanesulfinyl aldimines provides 1,2-disubstituted beta-amino alcohols in good yields (73-98%) and with high diastereoselectivities. Either syn- or anti-amino alcohol products can be obtained by the appropriate choice of alcohol protecting groups and/or reaction conditions. Finally, deprotection of the addition products provides straightforward access to either syn- or anti-1,2-amino alcohols.     

A highly efficient and direct approach for synthesis of enantiopure beta-amino alcohols by reductive cross-coupling of chiral N-tert-butanesulfinyl imines with aldehydes

A highly efficient and practical approach for the synthesis of optically pure beta-amino alcohols by the SmI2-induced reductive cross-coupling of chiral N-tert-butanesulfinyl imines with aldehydes was developed. This method allows the preparation of a broad range of chiral beta-amino alcohols, including functionalized ones under mild conditions. It provides a straightforward access to enantiopure beta-amino alcohols that are widely applicable in asymmetric synthesis.     

Highly efficient synthesis of chiral beta-amino acid derivatives via asymmetric hydrogenation

The Rh-TangPhos complex is an efficient hydrogenation catalyst for making chiral beta-amino acid derivatives. With the Rh-TangPhos system, high enantioselectivities (up to 99.6%) and turnover numbers have been obtained in the hydrogenation of E/Z isomeric mixtures of both beta-alkyl and beta-aryl beta-(acylamino)acrylates. [reaction: see text]