Diastereoselective Coupling Research Articles

Diastereoselective Three-Component Coupling Synthesis of Homoallylic Amines

Diastereoselective Three-Component Coupling Synthesis of Homoallylic Amines

‘GaI’: A new reagent for chemo- and diastereoselective C–C bond forming reactions

The potential of ‘GaI’ as a reductant in organic transformations, in particular C–C bond forming reactions involving α-functionalised ketones, has been investigated. Of most interest are the diastereoselective aldol coupling reactions of the α-alkoxy ketones, PhC(O)C(H)(OR)Ph, R = Me, Et or iPr, which give the novel γ-alkoxy, β-hydroxy ketones, PhC(O)C(H)(Ph)C(OH)(Ph)C(H)(OR)Ph, containing three contiguous stereogenic centres. The diastereostereoselectivity of these reactions was established from NMR spectroscopic and X-ray crystallographic studies of the products. When R = Me, the 2R,3S,4R/2S,3R,4S-enantiomeric pair is formed, whereas when R = Et or iPr, 2R, 3R, 4S/2S, 3S, 4R-diastereoisomers result. These differences are rationalised in terms of the likely transition states of the reactions. The same products are not formed when higher oxidation salts of gallium, or InI, are employed as the inorganic reagent. The reactivity of “GaI” towards α-halo ketones, a 1,2-diketone and α,β-unsaturated ketones has also been explored. Again, the outcomes of these reactions have been compared to those involving Ga(II) and Ga(III) reagents.

Highly Diastereoselective Preparation of anti-1,2-Diols by Catalytic Addition of Alkynylsilanes to α-Silyloxyaldehydes

The catalytic, diastereoselective coupling of alpha-silyloxy aldehydes and alkynylsilanes catalyzed by a nickel(0) N-heterocyclic carbene complex provides an effective entry to anti-1,2-diols. The scope of couplings and extent of diastereoselection are excellent across a range of substrates.

Studies on the Generation of Enolate Anions from Butane‐2,3‐diacetal Protected Glycolic Acid Derivatives and Subsequent Highly Diastereoselective Coupling Reactions with Aldehydes and Acid Chlorides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Studies Towards the Total Synthesis of Batzelladine A.

Application of a diastereoselective three-component coupling to the bicyclic core of the batzelladine alkaloids is described. The synthesis features the elaboration of glutamic acid by use of Eschenmoser sulfide contraction. An earlier approach is also included, which shows some limitations of dithiane chemistry when applied to the particular compounds required for this target.

Rh-catalyzed amination of ethereal Calpha-H bonds: a versatile strategy for the synthesis of complex amines.

Intramolecular CH insertion with sulfamates catalyzed by rhodium complexes offers an effective method for the preparation of N,O-acetals, which function as iminium ion precursors and undergo smooth diastereoselective coupling with nucleophiles under Lewis acidic conditions (see scheme). These findings advance the versatility of catalytic CH amination for the assembly of structurally complex nitrogen-containing products. Tf=trifluoromethanesulfonyl. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z460791_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Control of Diastereoselectivity in the Crotylation and Cinnamylation of Aldehydes by the Selection of Ligands on Allylic Indium Reagents.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Diastereomeric excess upon cleavage and reformation of diastereomeric alkoxyamines.

The thermal reactions of several TEMPO and DEPN (N-(2-methylpropan-2-yl)-N-(1-diethylphosphono-2,2-dimethylpropyl)-aminoxyl) based alkoxyamines were studied by means of (1)H and (31)P NMR spectroscopy aiming to distinguish the contributions of diastereoselective homolysis and coupling to the total equilibrium diastereomeric distribution. The TEMPO-based compounds reveal no diastereomeric excess while DEPN based compounds show a moderate excess both upon homolysis and coupling. The diastereomeric preference of homolysis for DEPN-(propionate-like) adducts does not depend on the ester group and it is mainly affected by the size of beta-substituents. The diastereoselective coupling is sensitive to the total recombination rate constant k(c) and diastereoselectivity increases with the decrease of k(c). Small diastereoselective coupling is found in the recombination of DEPN with sec-butyl isobutyrate radical, where no prochiral centers are formed upon cleavage of corresponding alkoxyamine.

Studies on the generation of enolate anions from butane-2,3-diacetal protected glycolic acid derivatives and subsequent highly diastereoselective coupling reactions with aldehydes and acid chlorides

Highly diastereoselective coupling reactions of enolates derived from butane-2,3-diacetal protected glycolic acids 1 and 2 and their alkylated derivatives with aldehydes are reported together with their efficient acid-catalysed deprotection to yield enantiopure anti-2,3-dihydroxyesters. A procedure to provide the corresponding syn-2,3-dihydroxyesters is also described in two cases, proceeding via an acylation-reduction sequence. An usual double addition reaction of butane-2,3-diacetal protected glycolic acid to small aliphatic acid chlorides provides a synthetically useful, densely-functionalised lactone after acidic deprotection.

Palladium‐Catalyzed α‐Arylation of Esters and Amides under More Neutral Conditions.

Two procedures for the alpha-arylation of carbonyl compounds under conditions that are more neutral than those of reactions of aryl halides with alkali metal enolates are reported. The first procedure rests upon the development of catalysts bearing the hindered pentaphenylferrocenyl di-tert-butylphosphine (Q-phos) and the highly reactive dimeric Pd(I) complex {P(t-Bu)3]PdBr}2. By this procedure, zinc enolates prepared from alpha-bromo esters and amides react with aryl halides to form alpha-aryl esters and amides in high yields under mild conditions with 1-2 mol % catalyst and with remarkable functional group tolerance. By the second procedure, silyl ketene and silyl ketimine acetals react with aryl bromides in the presence of substoichiometric zinc fluoride, 1 mol % Pd(dba)2, and 2 mol % P(t-Bu)3 in DMF solvent at 80 degrees C. Reactions of zinc tert-butyl acetate and propionate enolates and trimethylsilyl ketene acetals of tert-butyl propionate and methyl isobutyrate with aryl bromides bearing electron-donating and potentially reactive, base-sensitive electron-withdrawing groups and with pyridyl bromides are reported. In addition, the diastereoselective coupling of phenyl bromide with an imide enolate bearing the Evans auxiliary is reported, and this study shows that racemization of base-sensitive stereocenters does not occur during the coupling process under these more neutral conditions.

A short and efficient synthesis of (+)-prelactone B

The asymmetric total synthesis of (+)-prelactone B, a biologically important natural β-hydroxy-δ-lactone derivative that contains a 2,3- trans-dialkylpyran ring system, is described. This approach involves the use of a very efficient oxazolidinone-mediated anti-aldol reaction, and a diastereoselective coupling between a ketene silyl acetal with an aldehyde followed by lactonization.

Palladium-Catalyzed α-Arylation of Esters and Amides under More Neutral Conditions

Two procedures for the alpha-arylation of carbonyl compounds under conditions that are more neutral than those of reactions of aryl halides with alkali metal enolates are reported. The first procedure rests upon the development of catalysts bearing the hindered pentaphenylferrocenyl di-tert-butylphosphine (Q-phos) and the highly reactive dimeric Pd(I) complex {P(t-Bu)3]PdBr}2. By this procedure, zinc enolates prepared from alpha-bromo esters and amides react with aryl halides to form alpha-aryl esters and amides in high yields under mild conditions with 1-2 mol % catalyst and with remarkable functional group tolerance. By the second procedure, silyl ketene and silyl ketimine acetals react with aryl bromides in the presence of substoichiometric zinc fluoride, 1 mol % Pd(dba)2, and 2 mol % P(t-Bu)3 in DMF solvent at 80 degrees C. Reactions of zinc tert-butyl acetate and propionate enolates and trimethylsilyl ketene acetals of tert-butyl propionate and methyl isobutyrate with aryl bromides bearing electron-donating and potentially reactive, base-sensitive electron-withdrawing groups and with pyridyl bromides are reported. In addition, the diastereoselective coupling of phenyl bromide with an imide enolate bearing the Evans auxiliary is reported, and this study shows that racemization of base-sensitive stereocenters does not occur during the coupling process under these more neutral conditions.

Diastereoselective Synthesis of Quaternary Substituted Thioindolines from Sulfur Ylide Intermediates.

AbstractFor Abstract see ChemInform Abstract in Full Text.

New Synthetic Methods Using the TiCl4‐NR3 Reagent System

AbstractFor Abstract see ChemInform Abstract in Full Text.

Diastereoselective synthesis of quaternary substituted thioindolines from sulfur ylide intermediates

We have examined the coupling reactions of 2-thioindoles with vinyl diazoacetates in the presence of Rh(II) catalysts. While attempted enantio- and/or diastereoselective couplings using chiral catalysts and/or chiral auxiliaries on the vinyl diazoacetate have been largely unsuccessful, substrates having resident chirality on fused thiopyrans gave thioindolines with moderate to high diastereoselectivities.

An Asymmetric Synthesis of 3‐Aryl‐1,4‐oxazin‐2‐ones: Synthesis of a Key Intermediate of an NK1 Receptor Antagonist.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Control of diastereoselectivity in the crotylation and cinnamylation of aldehydes by the selection of ligands on allylic indium reagents.

Diastereoselective couplings of salicylaldehyde, anisaldehyde and 2-pyridylaldehyde with crotyl- and cinnamylindium reagents were studied. The syl/anti selectivity was found to depend largely on the ligands on the indium atom of the allylic indium reagents. A syn-selective cinnamylation of salicylaldehyde was realized by the combination of cinnamyl acetate and indium(I) iodide, whereas an anti-selective coupling with salicylaldehyde was achieved by the indium trichloride/aluminium-mediated cinnamylation.

New synthetic methods using the TiCl4-NR3 reagent system

Abstract The TiCl4-NR3 reagent system is useful for carbon-carbon bond forming reactions such as the aldol and related condensation reactions, the diastereoselective coupling of phenyl acetic acid derivatives, the conversion of aryl alkyl ketimines and ketoximes to pyrroles, ketazines to dihydrodiazines, enamines to aromatic amines, N,N-dialkylanilines to the corresponding benzidine derivatives, trialkylamines to unsaturated aldehydes, diarylcyclobutanones, diarylcyclobutylamine derivatives via iminium ion intermediates and for the reductive coupling of aromatic aldehydes, aldimines and intramolecular reductive coupling of chiral diimine derivatives. In all cases, the organic products are obtained in moderate to good yields, in singlepot operations under ambient reaction conditions. Hence, these synthetic methods have considerable synthetic potential.

Solid-phase synthesis of beta-mannosides.

The linkage of S-phenyl 2,3-di-O-benzyl-alpha-D-thiomannopyranoside to a cross-linked polystyrene support in the form of its 4,6-O-polystyrylborinate ester is described. The activation of this polymer-supported mannosyl donor is achieved at -60 degrees C in dichloromethane in the presence of 2,4,6-tri-tert-butylpyrimidine with the combination 1-benzenesulfinyl piperidine and trifluoromethanesulfonic anhydride. Addition of the donor alcohol at -60 degrees C followed by warming to room temperature and subsequent cleavage from the resin by gentle heating in aqueous acetone yields anomerically pure 2,3-di-O-benzyl-beta-D-mannopyranosides in excellent yield. Successful, diastereoselective coupling is demonstrated with a range of primary, secondary, and tertiary glycosyl acceptors, including typical carbohydrates and threonine derivatives.

Synthesis of an influenza neuraminidase inhibitor intermediate via a highly diastereoselective coupling reaction.

[reaction: see text]. A highly diastereoselective coupling reaction between TBSOP (3) and trityl sulfenimine 4 was developed which provided influenza neuraminidase inhibitor intermediate 7 in 80% yield and >99% de after crystallization. The reaction was shown to be reversible with the high diastereoselectivity resulting from a favorable H-bonding interaction in the major diastereomer.