Asymmetric indium-mediated Barbier-type allylation reactions with ketones to form homoallylic alcohol products

We report a general method for the enantioselective allylation of both aromatic and aliphatic ketones under indium-mediated Barbier-type conditions. Using 2 equiv of a commercially available amino alcohol, either (1S,2R)-(+)-2-amino-1,2-diphenylethanol ((+)-1) or (1R,2S)-(−)-2-amino-1,2-diphenylethanol ((−)-1) as the chiral auxiliary, good yields and enantioselectivities were achieved. To our knowledge, the enantioselectivities reported herein are the highest obtained for the indium-mediated allylations of ketones, specifically the homoallylic alcohol product obtained from the addition to α,α,α-trifluoroacetophenone provided 80% enantiomeric excess.     

Formation of homoallylic bromohydrins in indium-mediated allylation reactions of phenacyl bromides in aqueous solution

A method is described for carrying out indium-mediated allylation reactions of phenacyl bromides in aqueous solution that form homoallylic bromohydrins. By employing subsequent base treatment, the homoallylic bromohydrins were converted to allylic epoxides. Finally, the process has been used as a key step in a concise sequence for the synthesis of 3-allylbenzofuran.     

Stereoselective indium-mediated allylation of erythrulose derivatives in aqueous media

A range of erythrulose derivatives has been allowed to react with allyl bromide and metallic indium in THF or aqueous THF. Some of these allylations are highly stereoselective.     

An enantioselective indium-mediated allylation reaction of aldehydes and ketones in dichloromethane

An enantioselective indium-mediated addition reaction of allylic bromides to carbonyl compounds was achieved in dichloromethane in the presence of (−)-cinchonidine. The desired products were obtained in moderate to excellent yields and with up to 75% enantioselectivity.     

Tin mediated allylation reactions of enol ethers in water

Under tin-mediated Barbier-type reaction conditions, hydration of enol ethers takes place to form aldehydes that undergo allylation reactions. By using this process, various homoallylic alcohols and 2-halohomoallylic alcohols are produced in good to excellent yields.     

Synthetic and mechanistic studies of indium-mediated allylation of imines in ionic liquids

Aldimines derived from aryl and non-enolizable aliphatic aldehydes were allylated with allyl bromide mediated by indium powder in [bpy][BF4] (bpy = N-butylpyridine) to give good yields of the corresponding homoallylic amines. Selective formation of monoallylated amines can be achieved by varying the amount of bromide ion additive in the form of [bpy][Br]. The transient organoindium intermediates, allylindium(I) and allylindium(III) dibromide formed in the reaction, were studied by NMR spectroscopy to explain the selectivity.     

Fluorous tagging of DABCO through halogen bonding: recyclable catalyst for the Morita-Baylis-Hillman reaction

The halogen-bonded adduct between DABCO and two molecules of perfluorooctyl iodide (DABCO·(C(8)F(17)I)(2)) acts as a recyclable organocatalyst for the Morita-Baylis-Hillman reaction. This "supramolecular fluorous catalyst" is readily accessible and can be recovered by simple precipitation/filtration.     

Diastereoselective indium-mediated allylation of N-tert-butanesulfinyl ketimines: easy access to asymmetric quaternary stereocenters bearing nitrogen atoms

Indium-mediated allylation of N-tert-butanesulfinyl ketimines afforded in high yields and diastereoselectivities homoallylic amine derivatives with the nitrogen atom bonded to a quaternary stereocenter.     

Fluorous (trimethylsilyl)ethanol: a new reagent for carboxylic acid tagging and protection in peptide synthesis

Starting with a fluorous analogue of 2-(trimethylsilyl)ethanol, we have designed an easy method for preparing a new fluorous tag ((F)TMSE) for the protection of carboxylic acids. Because mild conditions are employed in the tag cleavage (TBAF in the presence of 4 A molecular sieves, which prevent racemization), this tag can be advantageously used in the synthesis of peptides and modified peptides, as we have demonstrated with several examples, including the fluorous synthesis of short alpha- and beta-peptides as well as of modified fluorinated retropeptides.     

Synthetic studies towards anti-SARS agents: application of an indium-mediated allylation of α-aminoaldehydes as the key step towards an intermediate

AG7088 was identified as a good starting point for modification, leading to an efficient and bio-available inhibitor for the SARS coronavirus main proteinase (SARS-CoV M^pro). Synthesis of intermediate 1 and analogues proceeded via a highly diastereoselective indium-mediated allylation of α-aminoaldehydes.     

A new strategy for the synthesis of hydroxylated pyrrolizidinic alkaloids by highly stereoselective indium-mediated allylation of pyrrolidinic aldehydes

Indium-mediated allylation of N-Cbz-l-prolinal 3, under Grignard conditions, was carried out with high yield and stereoselectivity (de = 90%) to afford intermediate (2S,1′R)-N-benzyloxycarbonyl-2-(1′-hydroxybut-3′-en-1′-yl)pyrrolidine 4, which was transformed in two steps into (1R,3R,7aS)-1-hydroxy-3-hydroxymethylpyrrolizidine 9. Commercial Cbz-l-proline was a source of functionalization and chirality.     

New indium-mediated cyclisation reactions of tethered haloenynes in aqueous solvent systems

The intramolecular cyclisation of tethered allyl bromides onto terminal alkynes mediated by metallic indium proceeds smoothly and cleanly in mixtures of THF and H₂O to give unsaturated carbocycles and heterocycles in good yield. Alternatively, the cyclisation may be carried out in anhydrous THF with the aid of acid catalysis. The reaction is also mediated by a range of indium salts and proceeds with substoichiometric quantities of indium in the presence of a co-reductant. Deuteration studies show that the reaction proceeds via a concerted syn carboindination of the carbon-carbon triple bond to give an intermediate, which is protonated in situ.     

Fluorous dienophiles are powerful diene scavengers in Diels-Alder reactions

[reaction: see text] Three fluorous dienophiles have been synthesized, and their value in scavenging an excess diene after Diels-Alder reactions is shown. The resulting fluorous derivatives are separated by solid-phase extraction on fluorous silica gel (FSPE). The fluorous [1,2,4]triazoline-3,5-dione 10 reacted with most dienes within seconds or minutes.     

Fluorous oxime palladacycle: a precatalyst for carbon-carbon coupling reactions in aqueous and organic medium

To facilitate precatalyst recovery and reuse, we have developed a fluorous, oxime-based palladacycle 1 and demonstrated that it is a very efficient and versatile precatalyst for a wide range of carbon-carbon bond formation reactions (Suzuki-Miyaura, Sonogashira, Stille, Heck, Glaser-type, and Kumada) in either aqueous or organic medium under microwave irradiation. Palladacycle 1 could be recovered through F-SPE in various coupling reactions with recovery ranging from 84 to 95% for the first cycle. Inductively coupled plasma optical emission spectrometry (ICP-OES) analyses of the Pd content in the crude product from each class of transformation indicated extremely low levels of leaching and the palladacycle could be reused four to five times without significant loss of activity.     

A recyclable electrochemical allylation in water

To develop environmentally benign processes for C-C bond formation, electrochemistry is applied in a tin-mediated allylation reaction in water. In this electrochemical process, the corresponding homoallylic alcohols are prepared in excellent yields, while both tin salt and water can be recycled and electrode materials are not consumed.     

Creation of quaternary stereocenters in carbonyl allylation reactions

Despite the advances in stereoselective carbonyl allylation reactions, the creation of quaternary stereocenters in the addition of 3,3'-disubstituted allylmetals to aldehydes is still a challenging issue. This feature article describes the most powerful approaches that have been devised to address this problem.     

Asymmetric synthesis of alpha-amino acids: indium-mediated reactions of glyoxylic oxime ether in aqueous media

The indium-mediated allylation and alkylation reactions of the Oppolzer camphorsultam derivative of glyoxylic oxime ether proceeded with excellent diastereoselectivity in aqueous media, providing a variety of enantiomerically pure alpha-amino acids.     

Organic reactions in water: an efficient method for the synthesis of 1,2,4-oxadiazoles in water

A simple and efficient process has been developed for the synthesis of 1,2,4-oxadiazoles in good yields through the reaction of amidoximes with anhydrides under catalyst-free conditions in water.