Green Synthesis and Regioselective Control of Sn/I2 Mediated Allylation of Carbonyl Compounds with Crotyl Halide in Water

Barbier-type carbonyl allylation is particularly useful due to ease of operation and the availability and tractability of allylic substrates,[1] Metals such as indium, zinc and tin are often used as the mediator. Here we present a green approach toward the synthesis, that is, Sn/I2 mediated allylation of carbonyl compounds with crotyl halide in water.     

Regio- and enantiospecific rhodium-catalyzed arylation of unsymmetrical fluorinated acyclic allylic carbonates: inversion of absolute configuration

The transition metal-catalyzed allylic substitution with unstabilized carbon nucleophiles represents an important cross-coupling reaction for the construction of ternary carbon stereogenic centers. We have developed a new regio- and enantiospecific rhodium-catalyzed allylic alkylation of acyclic unsymmetrical chiral nonracemic allylic alcohol derivatives with aryl zinc bromides. This study demonstrates that the hydrotris(pyrazolyl)borate rhodium catalyst and zinc(II) halide salt are crucial for efficiency, while the addition of lithium bromide to the catalyst is necessary for obtaining optimal regiospecificity. The stereochemical course of this reaction was established through the synthesis of (S)-ibuprofen, which demonstrated that the alkylation proceeds with net inversion of absolute configuration consistent with direct addition of the nucleophile to the metal center followed by reductive elimination.     

Sulfoxide-mediated Umpolung of alkali halide salts

A new protocol for the direct two-electron oxidative Umpolung of alkali halide salts is reported. This procedure, relying on the use of a commercially available sulfoxide as the oxidant, allows the electrophilic halogenation of carbonyl compounds as well as halolactonisation reactions to proceed from the corresponding sodium salts, at room temperature and under mild conditions.     

Rhodium-catalyzed asymmetric ring opening reactions of oxabicyclic alkenes: application of halide effects in the development of a general process

We have demonstrated halide effects in the rhodium-catalyzed asymmetric ring opening reaction of oxabicyclic alkenes. By employing halide and protic additives, the catalyst poisoning effect of aliphatic amines is reversed allowing the amount nucleophile to react in high yield and ee. Second, by simply changing the halide ligand on the rhodium catalyst from chloride to iodide, the reactivity and enantioselectivity of reactions employing an aromatic amine, malonate or carboxylate nucleophile are dramatically improved. Third, through the application of halide effects and more forcing reaction conditions, less reactive oxabicycle [2.2.1] substrates react to generate synthetically useful enantioenriched cyclohexenol products. Application of these new conditions to the more reactive oxabenzonorbornadiene permits the reaction to be run with very low catalyst loadings (0.01 mol %).     

A Mild and Simple Zinc-Promoted Barbier-Type Allylation of Aldehydes in Liquid Ammonia

The Barbier reaction of allylic bromides and carbonyl compounds can be carried out in liquid ammonia using commercial zinc powder.     

烯丙基卤和锡与醛, 酮反应合成高烯丙基醇

烯丙基溴或烯丙基碘和锡能以较高的产率与含有羟基、酚羟基、硝基、溴等活性基团的羰基化合物作用合成相应的高烯丙基醇, 文中讨论了不同卤素以及溶剂性质、水的含量对反应的影响。     

Regio- and enantiospecific rhodium-catalyzed allylic etherification reactions using copper(I) alkoxides: influence of the copper halide salt on selectivity

The transition metal-catalyzed allylic etherification represents a fundamentally important cross-coupling reaction for the construction of allylic ethers. We have developed a new regio- and enantiospecific rhodium-catalyzed allylic etherification of acyclic unsymmetrical allylic alcohol derivatives using copper(I) alkoxides derived from primary, secondary and tertiary alcohols. This study demonstrates that the choice of copper(I) halide salt is crucial for obtaining excellent regio- and enantiospecificity, providing another example of the effect of halide ions in asymmetric transition metal-catalyzed reactions. Finally, the ability to alter the reactivity of the alkali metal alkoxides in this manner may provide a useful method for related metal-catalyzed cross-coupling reactions involving heteroatoms.     

Noticeable facilitation of the bismuth-mediated Barbier-type allylation of aromatic carbonyl compounds under solvent-free conditions

When milled together with bismuth shot in the presence of allyl halide, aromatic aldehydes readily underwent a Barbier-type allylation to afford the corresponding homoallyl alcohols in good yield. In contrast to the failure in solution reaction, aromatic ketones also underwent allylic carbonyl addition under solvent-free conditions to give the expected tertiary homoallyl alcohols in moderate to good yield.     

Catalyzed cross-coupling of allyl bromides with allyl tin reagents

The reaction of allyl bromides with allyl tin reagents, catalyzed by palladium or zinc chloride gives cross-coupled products without allylic transpostion in the allyl halide partner but with predominate allylic rearrangement from the tin partner.     

Nucleophilic catalysis of halide displacement from brominated poly(isobutylene-co-isoprene)

The dynamics of halide displacement from brominated poly(isobutylene-co-isoprene)(BIIR) by carboxylate nucleophiles are detailed and discussed in terms of a general reaction mechanism. The exomethylene allylic bromide isomer within BIIR is shown to undergo simultaneous S_N2 alkylation of Bu₄Nacetate and S_N2′ rearrangement with Bu₄NBr. The latter generates a Z-BrMe isomer that is more reactive toward esterification. Hence, overall polymer modification rates are auto-accelerating, as Bu₄NBr liberated by esterification catalyzes allylic bromide rearrangement to a more reactive electrophile. This knowledge of reaction mechanisms is used to develop nucleophilic catalysis techniques involving iodide intermediates.     

Allylic alcohols as synthetic enolate equivalents: isomerisation and tandem reactions catalysed by transition metal complexes

Allylic alcohols can be isomerised into carbonyl compounds by transition metal complexes. In the last few years, catalyst design and development have resulted in highly efficient isomerisations under mild reaction conditions, including enantioselective versions. In addition, the isomerisation of allylic alcohols has been combined with C-C bond forming reactions when electrophiles such as aldehydes or imines were present in the reaction mixture. Also, C-F bonds can be formed when electrophilic fluorinating reagents are used. Thus, allylic alcohols can be treated as latent enol(ate)s. In this article, we highlight the latest developments concerning the isomerisation of allylic alcohols into carbonyl compounds, focusing in particular on tandem isomerisation/C-C or C-heteroatom bond formation processes. Significant attention is given to the mechanistic aspects of the reactions.     

Reactivity of Mitsunobu reagent toward carbonyl compounds

[reaction: see text] The nitrogen-based nucleophile generated from azodicarboxylate and triphenylphosphine displayed an excellent reactivity toward carbonyl compounds to generate a variety of different final products depending on the substituent pattern on the carbonyl carbon. From the structures of these adducts, a straightforward mechanistic interpretation for the formation of different products is provided.     

A mild and efficient method for the stereoselective formation of C-O bonds: palladium-catalyzed allylic etherification using zinc(II) alkoxides

[reaction: see text] A highly chemo- and stereoselective palladium-catalyzed allylic etherification reaction is described. The use of zinc(II) alkoxides proved effective in promoting the addition of the oxygen nucleophile derived from aliphatic alcohols to eta(3)-allylpalladium complexes. Using diethylzinc (0.5 equiv), 5 mol % of Pd(OAc)(2), and 7.5 mol % of 2-di(tert-butyl)phosphinobiphenyl in THF, the cross-coupling reaction between various aliphatic alcohols and allylic acetates proceeded at ambient temperature to furnish allylic ethers with high stereoselectivity.     

Homogeneously catalysed isomerisation of allylic alcohols to carbonyl compounds

Isomerisation of allylic alcohols forms an elegant shortcut to carbonyl compounds in a completely atom-economical process that offers several useful applications in natural-product synthesis and in bulk chemical processes. This review focuses on the heart of isomerisation catalysis: the catalyst. Combinations of transition metals (from Group 4 to 10), ligands and reaction conditions are compared with respect to yield, turnovers, rate and selectivity. A selected number of clever solutions to synthetic problems are highlighted, such as the synthesis of enols and enolates, chiral carbonyl compounds and silyl substituted ketones. Furthermore, a general overview of the mechanisms proposed for the isomerisation of allylic alcohols is given while some catalyst systems are singled out to discuss mechanistic research.     

Regioselective and stereoselective synthesis of tetrahydrofurans from a functionalized allylic silane and an aldehyde via formal [3+2]-cycloaddition reaction

Allylsilanes are known as useful reagents for the stereoselective formation of ring systems. Previous studies have shown that tetrahydrofurans can be constructed via formal [3+2]-cycloadditions of aldehydes and allylsilanes. A new challenge is to understand the intermediate, after a nucleophile attacks a carbonyl activated by the Lewis acid, in which two silyl-protected alkoxy groups with chemical equivalency could undergo formal cycloaddition reaction to afford a disubstituted and/or a trisubstituted tetrahydrofuran. Preparation of the protected α-hydroxy aldehyde and a functionalized allylic silane is discussed, as well as their formal cycloaddition reaction to form tetrahydrofurans.     

Geminal dicarboxylates as carbonyl surrogates for asymmetric synthesis. Part I. Asymmetric addition of malonate nucleophiles.

Asymmetric alkylations of allylic geminal dicarboxylates with dialkyl malonates have been investigated. The requisite allylic geminal dicarboxylates are prepared in good yields and high isomeric purities by two catalytic methods, ferric chloride-catalyzed addition of acid anhydrides to alpha,beta-unsaturated aldehydes and palladium-catalyzed isomerization and addition reactions of propargylic acetates. The complex of palladium(0) and the chiral ligand derived from the diamide of trans-1,2-diaminocyclohexane and 2-diphenylphosphinobenzoic acid most efficiently catalyzed the asymmetric process to provide allylic carboxylate esters with high ee. By systematic optimization studies, factors affecting the enantioselectivity of the reaction have been probed. In general, higher ee's have been achieved with those conditions which facilitate kinetic capture of the incipient pi-allylpalladium intermediate. These conditions also proved effective for achieving high regioselectivities. The minor regioisomeric product was formed when reactive substrates or achiral ligands were employed for the reaction, and could be minimized through the use of the chiral ligand. Under the established conditions, the alkylation of various gem-dicarboxylates afforded monoalkylated products in high yields with greater than 90% ee. The process constitutes the equivalent of an addition of a stabilized nucleophile to a carbonyl group with high asymmetric induction.     

Synthetic scope of Ru(OH)x/Al2O3-catalyzed hydrogen-transfer reactions: an application to reduction of allylic alcohols by a sequential process of isomerization/Meerwein-Ponndorf-Verley-type reduction

Reduction of allylic alcohols can be promoted efficiently by the supported ruthenium catalyst Ru(OH)x/Al2O3. Various allylic alcohols were converted to saturated alcohols in excellent yields by using 2-propanol without any additives. This Ru(OH)x/Al2O3-catalyzed reduction of a dienol proceeds only at the allylic double bond to afford the corresponding enol, and chemoselective isomerization and reduction can be realized under similar conditions. The catalysis is truly heterogeneous and the high catalytic performance can be maintained during at least three recycles of the Ru(OH)x/Al2O3 catalyst. The transformation of allylic alcohols to saturated alcohols consists of three sequential reactions: oxidation of allylic alcohols to alpha,beta-unsaturated carbonyl compounds; reduction of alpha,beta-unsaturated carbonyl compounds to saturated carbonyl compounds; and reduction of saturated carbonyl compounds to saturated alcohols.     

Palladium-catalyzed base- and solvent-controlled chemoselective allylation of amino acids with allylic carbonates

The utilization of readily available amino acids, which is not only an oxygen nucleophile but also a nitrogen nucleophile, in palladium-catalyzed allylic substitution is realized under mild conditions. The chemoselectivity and multiple allylation are controlled by adjusting the reaction conditions. This represents the first example of this convenient access to valuable N,O-diallylated amino acids. Under the title conditions, a range of amino acids (α-, β-, γ-) and dipeptides can be readily converted in to the corresponding allylic products with excellent yields (67 examples, up to 99% yield) as well as good functional group tolerance.     

In Situ Generation of Formaldehyde and Triphenylphosphine from (Hydroxymethyl)triphenylphosphonium and Its Application in Wittig Olefination

The reaction of (hydroxymethyl)triphenylphosphonium with benzylic or allylic halide under basic conditions at room temperature affords terminal alkenes in 61–89% yields. In this reaction, both formaldehyde and triphenylphosphine are in situ generated from (hydroxymethyl)triphenylphosphonium and further undergo Wittig olefination with benzylic or allylic halide.     

Direct preparation of allylic indium(III) reagents from allylic alcohols via a reductive transmetalation of pi-allylnickel(II) with indium(I) iodide

InI-mediated direct allylation of carbonyl compounds with allylic alcohols proceeded smoothly with catalytic amounts of Ni(acac)(2) and PPh(3) to give the corresponding homoallylic alcohols in high yields. Allylindium compounds were shown to be the real allylating agents in the present system. Substituted allylic alcohols gave branched homoallylic alcohols with syn-selectivity irrespective of the geometry of the starting allylic alcohols, whereas high anti-selectivity was observed when a bulky substituent is present in the allylic alcohols. The outcome of the diastereoselectivity is discussed on the basis of the reaction mechanism, comparing with the corresponding Pd-catalyzed version. Another distinct behavior between the Ni- and Pd-catalyzed allylation was demonstrated in the reaction of hex-1,5-diene-3,4-diol derivatives: the Pd catalyst did not give any coupling product, whereas the Ni-catalyzed InI-mediated reaction with benzaldehyde afforded the 1:1 and 1:2 adduct diols selectively depending on the reaction conditions.