Highly diastereoselective Michael addition of alpha-hydroxy acid derivatives and enantioselective synthesis of (+)-crobarbatic acid

[reaction: see text]. Michael addition of enolates of 2a and 2b to alpha,beta-unsaturated esters took place selectively on different faces (Si and Re, respectively) of the double bond to give the corresponding products 4 and 5, respectively, with >98% de. Subsequent hydrolysis of these Micheal adducts gives 3,4-disubstituted gamma-lactones with high enantiomeric excesses.     

Enantioselective solution- and solid-phase synthesis of glutamic acid derivatives via Michael addition reactions

The enantioselective conjugate addition of Schiff base ester derivatives to Michael acceptors either in solution (56–89% e.e.) or on solid-phase (34–82% e.e.) gave optically active unnatural α-amino acid derivatives. The reaction was conducted in the presence of chiral, non-racemic quaternary salts derived from the cinchona alkaloids using neutral, non-ionic phosphazene bases.     

Organocatalytic sequential Michael reactions: stereoselective synthesis of multifunctionalized tetrahydroindan derivatives

Multifunctionalized tetrahydroindan derivatives with four stereocenters were constructed via two sequential Michael reactions between cyclic γ,δ-unsaturated-β-ketoester and nitroalkenes initiated with 0.5-2 mol % of cinchona alkaloid based bifunctional organocatalysts and then with 1 equiv of tetramethylguanidine for cyclization. The desired products could be obtained in high yields (up to 99% yield) with excellent enantioselectivities (95-99% ee) as well as diastereoselectivities (up to >99:1 dr) even on a gram scale.     

Acyclic stereoselective boron alkylation reactions for the asymmetric synthesis of beta-substituted alpha-amino acid derivatives

Optically active syn- or anti-beta-substituted-alpha-amino acid derivatives are prepared in 94 to >/=99% ee and 66-98% ds by reaction of the Schiff base acetate of glycine tert-butyl ester with chiral, nonracemic B-alkyl-9-BBN derivatives in the presence of the Cinchona alkaloid, cinchonidine (CdOH) or cinchonine (CnOH), base, and lithium chloride.     

CamTHP*OH: a camphor-derived delta-lactol auxiliary for the effective desymmetrization of attached glycinamide residues. Asymmetric synthesis of alpha-amino carbonyl compounds

Stereoselective allylation of camphor and subsequent terminal hydroformylation affords a new delta-lactol auxiliary (camTHP*OH) on multigram scale. Stereoselective condensation with glycine dimethylamide and Cbz protection affords a camTHP*-desymmetrized glycinamide building block which undergoes efficient and highly diastereoselective metal enolate alkylation reactions. Acid-mediated deprotection affords the N-Cbz-protected alpha-amino amide products which may be converted directly to alpha-amino ketones on treatment with Grignard or organolithium reagents without loss of stereochemical integrity. [reaction: see text]     

Highly stereoselective synthesis of 1,3-aminoalcohols via Mannich reactions

Diastereoselective synthesis of β-amino ketones by a one-pot Mannich reaction and their subsequent reduction afforded sterically congested enantiomerically pure 1,3-aminoalcohols in high diastereoselectivity: dr up to >98:<2 over two steps. The absolute configurations of the newly created stereogenic centers were assigned by NMR spectroscopy and chemical correlation.     

Asymmetric wolff rearrangement reactions with alpha-alkylated-alpha-diazoketones: stereoselective synthesis of alpha-substituted-beta-amino acid derivatives

Photoinduced asymmetric Wolff rearrangement reactions were performed with alpha-amino-alpha'-methyl-alpha'-diazoketones to afford alpha-methyl-beta-amino acid esters with good stereoselectivity. Factors that may influence the stereochemistry were examined, including steric effects and temperature dependence, which had a great impact on the stereochemistry.     

Highly stereoselective synthesis of trisubstituted vinylcyclopropane derivatives via arsonium ylides

[reaction: see text] Alkylidene or arylidene malonates reacted with arsonium allylides to give trans-disubstituted cyclopropane-1,1-dicarboxylates with high stereoselectivity in high yields. The mechanism of the cyclopropanation reactions has also been investigated.     

First highly stereoselective synthesis of anti-alpha-trifluoromethyl-beta-amino acid derivatives

The Reformatsky-type reaction of 2-bromo-3,3,3-trifluoropropanoic imide with various types of imines, in the presence of ZnBr2 as a Lewis acid in THF at 0 degrees C for 3 h, gave the corresponding alpha-trifluoromethyl-beta-amino acid derivatives in a highly anti-selective manner.     

Highly stereoselective addition reactions of metallated trans-1,3-dithiane-1,3-dioxide to aldehydes

The sodium anion of trans-1,3-dithiane-1,3-dioxide reacts with unhindered aromatic and heteroaromatic aldehydes to give adducts with 95:5 to 97:3 diastereoselectivity.     

Studies in asymmetric synthesis. Highly stereoselective reactions of organosulfur compounds

The history of and need for asymmetric syntheses are reviewed briefly with special mention of recently developed methods of high efficiency. The conditions for a viable asymmetric synthesis are stated. Highly stereoselective syntheses involving sulfonium salts and 1,3-dithianes are detailed.     

Iminium ion cyclizations. Highly stereoselective synthesis of substituted tetrahydroisoquinoline derivatives

Cationic cyclizations of acyliminium ions $\text{2}$ (R₁  phenyl) occur with high stereo-selectivity, which is suggested to originate in the intermediate arenium ions.     

Highly regio- and stereoselective synthesis of indene derivatives via electrophilic cyclization

[reaction: see text] Indene or naphthalene derivatives are readily prepared in moderate to excellent yields with high regio- and stereoselectivity under very mild reaction conditions by the reaction of acetylenic malonates and ketones with I2, ICl, or NIS. The resulting iodides can be further elaborated using palladium-catalyzed coupling reactions.     

Michael addition approach for the synthesis of novel spiro compounds and 2-substituted malonic acid derivatives from Meldrum’s acid

Novel routes for the synthesis of spiro derivatives of Meldrum’s acid and 2-substituted malonic acid derivatives have been developed. Meldrum’s acid was monoalkylated using a Michael addition reaction. Mono-Michael adducts were then alkylated using substituted haloalkanes, which on condensation gave spiro derivatives of Meldrum’s acid. Bis Michael addition of Meldrum’s acid with 1,5-diaryl-1,4-pentadien-3-one gave directly a spiro derivative of Meldrum’s acid. These compounds and bis alkylated Meldrum’s acid derivatives, on acidic methanolysis gave 2-substituted malonic acids.     

Photoinduced diastereoselective addition of perfluoroalkyl iodides to acrylic acid derivatives for the synthesis of fluorinated amino acids

Photoinduced diastereoselective addition of perfluoroalkyl iodides in the presence of an aqueous solution of Na2S2O3 was an excellent method for iodoperfluoroalkylation of acrylic acid derivatives bearing a chiral auxiliary, with moderate to good stereoselectivities and with no detectable side products. The iodoperfluoroalkylation of N-acyloylcamphorsultam provided a convenient route for preparing chiral fluorine-containing amino acids.     

Highly regio- and stereoselective synthesis of tricyclic frameworks using Baylis-Hillman derivatives

A simple and convenient synthetic route for the synthesis of tricyclic chromeno[4,3-b]pyrrolidine frameworks using Baylis-Hillman bromides involving in situ formation of an imine, decarboxylation and a [3+2] cycloaddition sequence is described.     

Highly stereoselective aldol reaction for the synthesis of gamma-lactones starting from tartaric acid

A simple stereoselective process for the synthesis of highly substituted gamma-lactones was developed based on aldol reactions between the enolate of dioxanes derived from tartaric acid and aldehydes. A range of aromatic and aliphatic aldehydes were reacted, in most cases achieving good yields and stereoselectivity. The limitations of this reaction were identified and a transition state is proposed.     

Highly stereoselective addition of stannylcuprates to alkynones

The addition of stannylcuprate reagents such as (Bu3Sn)(PhS)CuLi to alkynones has been found to proceed in high yield and with excellent stereoselectivity for the Z isomer of the product (>95%). The behavior of the stannylcuprates is thus very different from that of their "carbocuprate" counterparts such as Me2CuLi or Me2Cu(CN)Li2 which are nonstereoselective. Furthermore, in contrast to the reactions of (R3Sn)(PhS)CuLi with the corresponding alkynoates, the presence of a proton source in the reaction medium has no effect on the stereoselectivity of the reaction of alkynones.     

The efficient enantioselective synthesis of dihydropyrans via organocatalytic Michael addition reactions

An asymmetric Michael addition of α-cyanoketones to α,β-unsaturated aldehydes to form chiral dihydropyrans catalyzed by l-diphenylprolinol trimethylsilyl ether is presented. A series of 3,4-dihydropyrans were obtained in excellent yields (up to 91%) and enantioselectivities (up to 98% ee). A plausible mechanism for this process is proposed.     

Asymmetric synthesis of 3-methylthio alcohols by intramolecular Michael addition reactions

Chiral 3-methylthio alcohols have been synthesized through a known intramolecular sulfur transfer reaction that has been carried out in di- and trisubstituted α,β-unsaturated N-enoyl oxazolidinethiones as substrates, giving rise to syn/anti-diastereomers. The anti-diastereomer is favored and obtained via a highly diastereoselective protonation step.