Ruthenium-catalyzed regioselective deuteration of alcohols at the β-carbon position with deuterium oxide

A convenient method for regioselective H/D exchange between D(2)O and alcohols at the β-carbon position using the catalytic system [(p-cymene)RuCl(2)]/ethanolamine/KOH is described. This method is applicable for deuteration of both primary and secondary alcohols. The H/D exchange reactions proceed through an oxidation/modification/reduction reaction sequence. Alcohols are first temporarily oxidized to carbonyl compounds by the hydrogen transfer catalyst. The carbonyl compounds then undergo deuteration at the carbon adjacent to the carbonyl group by keto-enol tautomerization in the presence of D(2)O and a catalytic amount of base. The deuterated carbonyl compounds are then reduced to produce deuterated alcohols. In support of the reaction mechanism, a well-defined bimetallic ruthenium complex was isolated from the reaction of [{(p-cymene)RuCl(2)}(2)] with ethanolamine. The activity of this complex is similar to that of [{(p-cymene)RuCl(2)}(2)]/ethanolamine.     

Phosphonium salt induced stereoselective allylic rearrangement during chlorination of α-hydroxyallylphosphinates

α-Hydroxyallylphosphinates were stereoselectively converted to γ-chloro allylphosphinates when treated with Ph₃P and CCl₄, via substitution of hydroxyl and migration of double bond. The reaction was promoted by phosphonium cation that acted as Lewis acid.     

A novel and expedient synthesis of optically active fluoroalkylated amino acids via palladium-catalyzed allylic rearrangement and Ireland–Claisen rearrangement

The allylic substitution reactions of various chiral α-fluoroalkylated mesylates with carboxylic acids in the presence of a palladium catalyst proceeded smoothly to give γ-fluoroalkylated allyl esters in excellent yields. The esters were subsequently subjected to Ireland–Claisen rearrangement without isolation, leading to the corresponding homochiral α-fluoroalkylated-β,γ-unsaturated amino acids in good yields.     

Palladium-catalyzed allylation of α-isocyanocarboxylates

α-Isocyanocarboxylates underwent palladium-catalyzed allylation with allylic acetates, in which π-allylpalladium(II) intermediate was involved. The catalytic allylation of methyl α-isocyano(phenyl)acetate using an optically active ferrocenylphosphine ligand caused an asymmetric induction of up to 39% ee.     

Enantioselective electrophilic bond construction to the α-carbon of α-aminoacids

In this report, we describe three possibilities for aminoacid synthesis using an enantioselective electrophilic process. Thus, enantioselective carboxylation, alkylation and protonation of Schiff bases yield optically active aminoacids with e.e. up to 76%.     

Ester-enolate Claisen rearrangement of proline-containing α-acyloxy-α-vinylsilane. Synthesis of pyrrolidine-fused glutamate analogs

The stereoselective syntheses of pyrrolidine-fused aspartate and glutamate analogs, (S)-α-carboxymethyl-proline 3 and (S)-α-2-carboxyethyl-proline 4, using a chirality-transferring ester-enolate Claisen rearrangement of α-vinyl-α-acyloxysilane having a Boc-Pro as an acyloxy group, are described. The stereochemical outcome of the proline ester-derived ester-enolate Claisen rearrangement is also disclosed.     

Diastereoselectivity in the Carroll rearrangement of β-keto esters of tertiary allylic alcohols

Carroll rearrangement of β-keto esters derived from tertiary allylic alcohols, for example, 7, under basic conditions followed by decarboxylation of the resulting β-keto acids yielded the expected γ,δ-unsaturated methyl ketones 8 with a range of olefin geometries from 100:0 to 1:1.8 E/Z, depending on the relative steric requirements of the two groups at the allylic center.     

A neighbouring group effect leading to enhanced nucleophilic substitution of amines at the hindered α-carbon atom of an α-hydroxyphosphonate

Diethyl α-hydroxy-benzylphosphonate undergoes nucleophilic substitution with primary amines of sufficient reactivity at around 100 °C to afford the corresponding α-aminophosphonates. The substitution can be enhanced by microwave irradiation. The reaction takes place with surprising ease due to the neighbouring group effect of the PO moiety as was justified by DFT calculations carried out to evaluate the mechanism of the substitution under discussion.     

Acid-catalyzed rearrangement of α-hydroxytrialkylsilanes

Cationic rearrangement of several α-hydroxysilanes is described. Treatment of both (1R,1′R,2′S)-α-hydroxycyclopropylsilane syn-9 and (1S,1′R,2′S)-anti-9 under aqueous H₂SO₄ underwent rearrangement via a common α-silyl cation intermediate A to give a mixture of the ring-opened (R)-vinylsilane 13, the tandem [1,2]-CC bond migration product (1R,2S,1′R)-14, and its 1′S isomer 15. On the other hand, the acidic treatment of (R,E)-α-hydroxyalkenylsilane 8 or (R,Z)-8 was each accompanied with partial racemization to give an enantiomeric isomer of allylic alcohol 23 via a preferential syn-facial S_N2′ reaction, respectively. Both α-hydroxyalkynylsilane 6 and α-hydroxyalkylsilane 12 were inert to the acidic conditions; however, treatment of (R)-α-mesyloxyalkynylsilane 26 under aqueous H₂SO₄ gave a mixture of the optically active rearranged allene 27, α,β-unsaturated ketone 28, and (S)-α-hydroxyalkynylsilane 6 with partial racemization. Comparisons of the reactivities of these α-hydroxysilanes under acidic conditions are also disclosed.     

Synthesis of stable oxazolidine nitroxyl radicals with methoxy groups at the α-carbon atoms to the radical site

The condensation of -hydroxyaminoalcohols with aldehydes and acetone gave 3-hydroxyoxazolidines and tautomeric N-(2-hydroxyethyl)--arylnitrones, whose oxidation by PbO₂ in methanol leads to stable oxazolidine nitroxyl radicals with methoxy groups at C² and C⁴.Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk 630090. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 4, pp. 966–973, April, 1992.     

Synthesis of γ-fluoro-α-amino acids by Claisen rearrangement

A series of N-protected glycine and alanine esters 4-7 of different fluorinated allylic alcohols 1 was prepared using the dicyclohexylcarbodiimide/dimethylaminopyridine method. All fluorinated esters of this type failed to react in an esterenolate Claisen rearrangement under the general conditions of the Kazmaier variant of this rearrangement. Change of the solvent from tetrahydrofuran to the less coordinating diethyl ether enabled the rearrangement of N-Boc-protected glycine esters 4a-c of 2-fluoroalken-3-ols 1a-c to form N-Boc-2-amino-4-fluoroalk-4-enecarboxylic acids 8a-c, while the rearrangement failed with N-Boc-alanine esters and all amino acid esters of 2-fluoroallylic alcohol (1e). This might be due to competing deprotonation of the position β to fluorine. Similarly to the esters 4a-c, the TFA-protected glycine esters 5a-c of 2-fluoroalken-3-ols 1a-c were rearranged. Deprotection of the Boc or the TFA group under salt-free conditions yielded the free amino acids 11a-c, which might be seen as mimics for N-alkylasparagines a group of lipoproteins.     

Synthesis of γ,δ-unsaturated quaternary α-alkylamino acids using umpolung reaction and Claisen rearrangement

A new synthesis of γ,δ-unsaturated quaternary α-amino acid derivatives was developed utilizing N-alkylation and Claisen rearrangement of allyl α-iminocarboxylates.     

Synthesis of C-glycoside analogues of α-galactosylceramide via linear allylic C-H oxidation and allyl cyanate to isocyanate rearrangement

C-Glycoside analogues of α-galactosylceramide were synthesized in which several significant modifications known to promote Th-1 cytokine production were included. The key transformations include C-H oxidation, Sharpless asymmetric epoxidation, olefin cross metathesis, and an allyl cyanate to isocyanate rearrangement.     

Theoretical studies on the photoinduced rearrangement mechanism of α-santonin

α-Santonin is the first organic compound observed to feature a photoinduced rearrangement and is now known to undergo a series of photochemical processes under UV irradiation. On the basis of the considerable interest of this system as a prototype, and of the yet limited insights reached for the basic photo mechanisms, we calculate the high-level electronic structures and explore the potential energy surfaces (PES) of α-santonin in the ground and lowest-lying excited states, their couplings, and the possible photoinduced isomerization pathways. The calculations identify the low-lying singlet excited state (1)(nπ*) accessible under light irradiation, which decays to the low-energy (3)(ππ*) state through an intersystem crossing in the Franck-Condon region to initiate the photoinduced rearrangement. The initial reaction from the C3-C5 bond coupling, which takes place on the (3)(ππ*) state potential energy surface, leads to a three-membered alkyl-ring compound intermediate state INT. The following photochemical reactions have the possibility to arise from two distinct C-C bond cleavages, C4-C5 and C3-C4, denoted as path A and path B. Path A is favored both dynamically on the excited-state PES and thermodynamically on the ground-state PES in vacuo. Experiments show that it also becomes the dominant photoinduced rearrangement process in the crystal, which can be explained by considering the requirement for less space and the stacking effect under the confined environment. Path B is dynamical advantaged both on the ground- and excited-state PESs in a weak polar solvent, such as dioxane. Once the biradical intermediate B-INT is accessible on the ground-state PES, the formation of the product B-P is almost barrier free.     

Copper-catalyzed regioselective allylic oxidation of olefins via C–H activation

A regioselective oxidation of allylic C–H bond to C–O bond catalyzed by copper (I) was developed with diacyl peroxides as oxidants. The oxidation of allylic C–H bond was accomplished with good yield and regioselectivity under mild reaction conditions. This method has a broad substrate scope including cyclic olefins, terminal and internal acyclic olefins and allyl benzene compounds. The reaction proceeds by a radical mechanism as suggested by spin trapping experiments.     

An Ireland–Claisen rearrangement/RCM based approach for the construction of the EF-ring of ciguatoxin 3C

The EF-ring of ciguatoxin 3C, a marine toxin from the dinoflagellate Gambierdiscus toxicus, was stereoselectively synthesized by iterative use of a cyclic ether formation process based on chirality-transferring Ireland-Claisen rearrangement and ring-closing olefin metathesis.     

Intramolecular trapping of a cyclopropylidenamine during the favorskii rearrangement of α-chloroketimines

Cyclopropylidenamines have been trapped for the first time in an intramolecular way during the Favorskii rearrangement of suitably functionalized α-chloroketimines.     

Transannular Claisen rearrangement reactions for the synthesis of vinylcyclobutanes: formal synthesis of (±)-grandisol

Unsaturated eight-membered lactones undergo decarboxylative and non-decarboxylative transannular Ireland-Claisen rearrangement reactions, to give substituted vinylcyclobutanes. A formal synthesis of (±)-grandisol is described.