Metal-mediated Allylation Research Articles

Thermal, Spectroscopic, and Crystallographic Analysis of Mannose-Derived Linear Polyols

The major diastereomer formed in the Barbier-type metal-mediated allylation of d-mannose has previously been shown to adopt a perfectly linear conformation, both in solid state and in solution, resulting in the formation of hydrogen-bonded networks and subsequent aggregation from aqueous solution upon stirring. Here, a comprehensive study of the solid state structure of both the allylated d-mannose and its racemic form has been conducted. The binary melting point diagram of the system was determined by differential scanning calorimetry analysis, and the obtained results, along with structure determination by single crystal X-ray diffraction, confirmed that allylated mannose forms a true racemate. Further examination by powder X-ray diffraction and CP MAS 13C NMR spectroscopy revealed polymorphism both in the pure enantiomer and in the racemate. In addition, the propargylated and hydrogenated analogues of allylated d-mannose were prepared and subjected to thermal and spectroscopic analyses. The crystal structure of the propargylated compound was successfully determined, showing a linear molecular conformation similar to that found for allylated d-mannose. Both new compounds likewise display aggregation behavior in water, further verifying that the low-energy linear conformation plays a significant role in this unusual behavior of these rodlike mannose derivatives.

Metal-mediated allylation of enzymatically oxidized methyl α- d-galactopyranoside

The C-6 unit of methyl α- d-galactopyranoside was selectively modified by combining enzymatic oxidation with an indium-mediated allylation reaction. The Barbier–Grignard type reaction, where a carbonyl group reacts with an allyl halide, proceeds in aqueous solution, even with water as the only solvent; thus carbohydrates can be modified without the need for drying or protection–deprotection steps. The corresponding homoallyl alcohols are produced in high yields of >90% in the reactions with allyl bromide and cinnamyl chloride. The main products were isolated and characterized by GC–MS and NMR spectroscopy.

Converting Unprotected Monosaccharides into Functionalised Lactols in Aqueous Media: Metal‐Mediated Allylation Combined with Tandem Hydroformylation–Cyclisation

From biomass to fine chemicals: A highly regioselective reaction sequence (see scheme) combining a metal-mediated allylation and tandem hydroformylation-cyclisation for converting unprotected monosaccharides into multifuntionalised lactol structures is presented. The reaction sequence is performed in aqueous media without the need for any protective groups.

Expeditious biomimetically-inspired approaches to racemic homocitric acid lactone and per-homocitrate

Two concise and flexible biomimetically-inspired approaches to homocitric acid lactone ( 3) and its higher homolog, triethyl per-homocitrate ( 12), are presented herein. The key steps include an efficient indium metal-mediated allylation–oxidative cleavage procedure and a one-step ethoxycarbonylmethylation of α-oxo-diesters.

General and Practical Approach to the Syntheses of Linear Homoallylic Alcohols

AbstractFor Abstract see ChemInform Abstract in Full Text.

Indium‐Mediated Allylation of Hydroxyphthalides with Acetic Acid as an Additive.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Indium-Mediated Allylation of Hydroxyphthalides with Acetic Acid as an Additive

Phthalide derivatives represent an important class of naturally occurring lactone. Some of these compounds showed a biological activity and also have been used in the treatment of diseases. A lot of synthetic methods were developed and reported for preparation of phthalide derivatives as target molecules and starting materials for preparation of other natural products. Among metalmediated allylation reactions, indium-mediated allylation has gained popularity in view of the possibility of carrying out the reaction in water and showing different pattern of diastereoselectivity. The organic reaction in aqueous solution can save time and cost by evading a consuming protection and deprotection sequence for certain functional groups containing acidic moiety such as carboxylic acid and alcohol. Here we report an efficient allylation of hydroxyphthalides 1a and 1b using various allyl bromides and indium in THF in the presence of 1 equiv. of acetic acid (Scheme 1). The allylations in aqueous THF were attempted as well for comparison. For the optimization of allylation, the ratio of indium and cinnamyl bromide in the reactions was fixed in 1 : 1.5 on the assumption of reactive species of allyl indium as a sesquidimeric species. The allylation reaction of hydroxyphthalide 1a in THF (entry 1, Table 1) was slow and gave a cinnamylated phthalide in low yield even after 24 h due to incomplete reaction. By the addition of water (entry 2), 1 equiv. of 1 N HCl (entry 3) or 0.5 equiv. of acetic acid (entry 4) to THF reaction solution as a cosolvent or additives, the allylation gave a cinnamylated phthalide in quantitative yield with increased diastereoselectivity and reduced reaction time as shown in Table 1. The reaction in the presence of acetic acid is turned out to be faster than that in aqueous solution. Acetic acid rather than 1 N HCl solution was a choice of acid additive because of fast reaction rate, easy handling and better diastereoselectivity. 1 equiv. of Acetic acid was found to be optimum amount in both reaction rate and diastereoselectivity (entry 5). The reactions of 3-hydroxyphthalide 1a with various allyl bromides in THF in the presence of 1 equiv. of acetic acid were examined (Method B) and the results are shown in Table 2. The reactions also were tried in aqueous THF (THF : H2O = 4 : 1) for a comparison (Method A). Generally, the reaction under Method B is faster than that under Method A. The allylations of hydroxyphthalide 1a with various allyl bromides under two conditions gave the corresponding products in high yields in the most cases (entries 1, 2 and 46, Table 2), whereas the propargylation of hydroxyphthalide 1a with propargyl bromide in aqueous THF did not gave any product. The reaction with propargyl bromide in THF in the presence of acetic acid gave the two products, propargyl and allenyl phthalide in 46% and 27% yields, respectively (entry 3). The allylation of phthalide 1a with crotyl bromide under the reaction conditions almost did not show any diastereoselectivity (entry 5). In the reaction of allyl bromides with substituents at γ-position, only the product resulting from γattack was produced (entries 2, 5 and 6). The reaction did not seem to proceed through the oxocarbenium ion C generated from a phthalide 1a under the our present conditions but through allylation of carboxybenzaldehyde A in the equilibrium with 3-hydroxyphthalide 1a followed by lactonization. Even if internal chelation effect of indium reagent by carboxylate has been known, it is not clear that it is operative in our phthalide system under our reaction condition. We next examined allylation of 3-hydroxy-3-methylphScheme 1 Table 1. Allylation of hydroxyphthalide 1a with cinnamyl bromide

General and practical approach to the syntheses of linear homoallylic alcohols

Abstract We have demonstrated that metal-mediated allylation of aldehydes can afford γ-homoallylic alcohols or α-linear homoallylic alcohols by judicious choice of the solvents. A new mechanism has been proposed to account for this new α-selective metal-mediated allylation reaction. On the other hand, the metal-mediated prenylation under the same conditions to obtain α-prenyl alcohols was unsuccessful. Detailed mechanistic studies have resulted in the discovery of a new method to obtain compounds with diverse structures via an oxonium-ene cyclization. Suppressing the oxonium-ene reaction during the reaction has resulted in the formation of α-prenyl alcohols. A highly enantioselective process to obtain α-prenyl product in high optical purity has also been accomplished.

Consecutive Proline-Catalyzed Aldol Reactions and Metal-Mediated Allylations: Rapid Entries to Polypropionates

A concise method for the rapid construction of polypropionate-type structures by consecutive organocatalytic aldol and metal-mediated allylation reactions is described.

Development of a Highly α‐Regioselective Metal‐Mediated Allylation Reaction in Aqueous Media: New Mechanistic Proposal for the Origin of α‐Homoallylic Alcohols.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Metal-mediated allylation of mucohalic acids: facile formation of γ-allylic α,β-unsaturated γ-butyrolactones

Mucohalic acids {mucochloric acid ( 1 , 3,4-dichloro-5-hydroxy-5 H-furan-2-one and mucobromic acid ( 2 , 3,4-dibromo-5-hydroxy-5 H-furan-2-one)} were employed as aldehydes in the indium- and tin-mediated Barbier-type allylation reactions and afforded γ-allylic α,β-unsaturated γ-butyrolactones in good to excellent yield.

Development of a highly alpha-regioselective metal-mediated allylation reaction in aqueous media: new mechanistic proposal for the origin of alpha-homoallylic alcohols.

This paper described a general method to obtain alpha-adduct homoallylic alcohols using indium, zinc, and tin in water. A new mechanism was proposed to account for the formation of these synthetically difficult-to-obtain molecules. Generally, this method can be performed with a wide range of aldehydes and allylic halides with just 6 equiv of water added, giving the alpha-adduct in high selectivities. To account for the origin of the alpha-homoallylic alcohol, the reaction mechanism was carefully studied using (1)H NMR, a crossover experiment, and the inversion stereochemical studies of 22 beta gamma-adduct homoallylic sterol to the 22 alpha alpha-adduct homoallylic sterol. From the results of mechanism studies, it is possible that two mechanism pathways coexisted in the metal-mediated alpha-regioselective allylation. The metal salts formed from the metal-mediated allylation can catalyze the gamma-adduct to undergo a bond cleavage to generate the parent aldehyde in situ followed by a concerted rearrangement, perhaps a retroene reaction followed by a 2-oxonia[3,3]-sigmatropic rearrangement to furnish the alpha-adduct. The alpha-adduct can also be synthesized via the formation of an oxonium ion intermediate between the gamma-adduct and the unreacted aldehyde. The proposed mechanisms were further supported by experimental findings from the addition of InBr(3) to gamma-adduct under similar conditions.

Cadmium metal-mediated allylation of carbonyl compounds

Metallic cadmium prompted Barbier-type coupling of carbonyl compounds and allylic halides. The reaction was regio-selective homoallylic alcohols coupled at the γ-position of allylic halides, α,β-Unsaturated carbonyl compounds underwent only 1,2-addition.