Transition metal catalyzed nucleophilic allylic substitution: activation of allylic alcohols via π-allylic species

Modern organic synthesis now requires efficient atom economical synthetic methods operating under greener pathways to achieve C-C and C-heteroatom bond formation. Direct activation of allylic alcohols in the presence of transition metal catalysts leading to electrophilic π-allyl metal intermediates represents such a promising target in the field of nucleophilic allylation reactions. During the last decade, this topic of recognized importance has become an emerging area, and selected transition metals, sometimes associated with alcohol activators, have brought elegant solutions for performing allylic substitution directly from alcohols in a regio, stereo and enantioselective manner.     

SN2-Selective allylic substitution of chiral γ-aryl substituted allylic picolinates with alkynylcopper reagents

Substitution of γ-aryl secondary allylic picolinates with alkynyl copper reagents was studied. The copper reagent, prepared from TMSCCMgBr and CuBr·Me₂S in 2:1, was subjected to substitution of the picolinate derived from (E)-3-phenyl-1-methyl-2-propenyl alcohol at 0 °C for 1 h in THF to produce a mixture of α- and γ-products and the alcohol in 67:20:13, while the reagent in 3 or 4:1 ratio gave the α-product with 90-91% selectivity. On the contrary, reaction in CH₂Cl₂-THF (6-8:1) at 0 °C for 1 h furnished the α-product with 99% regioselectivity. The effect of CH₂Cl₂ was also demonstrated with eight more examples. Furthermore, 99% inversion was determined by transformation to the literature compound and by chiral HPLC.     

Iron-catalyzed esterification of allylic sp3 C–H bonds with carboxylic acids: Facile access to allylic esters

The first general and efficient iron-catalyzed esterification of allylic sp³ C–H bonds with carboxylic acids using ionic iron(III) complexes (1–4) as a catalyst and DTBP (DTBP = di-tert-butyl peroxide) as an oxidant is achieved. A variety of allylic esters were synthesized in good to excellent yields using the ionic iron(III) complex 2 as a catalyst in a 5 mol% loading. This reaction is characterized by its high efficiency, broad substrate scope with excellent steric hindrance tolerance and good functional group compatibility.     

Ligand coupling through σ-sulfurane — complete retention of geometric configuration of allylic and vinylic groups in the reactions of allylic and vinylic sulfoxides with Grignard reagents

The reaction of p-benzenesulfonylphenyl crotyl sulfoxide with Grignard reagents is considered to proceed via formation of an incipient σ-sulfurane to afford the coupling product, p-benzenesulfonyl-crotylbenzene, in which the geometric configuration of crotyl group was completely preserved. No rearrangement was observed in the coupling reaction of p-benzenesulfonylphenyl α-methylallyl sulfoxide. Such a complete retention of geometric configuration was also found in the reactions of 2-pyridyl and p-benzenesulfonylphenyl styryl sulfoxides with Grignard reagents.     

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.     

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.     

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.     

Copper-catalyzed γ-selective and stereospecific allylic alkylation of ketene silyl acetals

Copper-catalyzed allylic alkylation of ketene silyl acetals proceeded with excellent γ-E-selectivity. Efficient α-to-γ chirality transfer with anti-selectivity occurred in the reaction of enantioenriched secondary allylic phosphates, affording enantioenriched β-branched γ,δ-unsaturated esters. Excellent functional group compatibility was observed.     

An allylic nucleophilic substitution reaction of 1α-hydroxyvitamin D derivatives

The first transformation of the 5,6- trans-vitamin D conjugated triene system into that of isovitamin D occurring under nucleophilic conditions is observed in the reaction of 5 with n-butyl-lithium to give 6.     

Oxidation of fluoroalkyl-substituted allylic alcohols: a synthesis of fluorinated α,β-epoxyketones

Fluoroalkyl-substituted allylic alcohols are readily and selectively oxidized at the hydroxyl group with the Swern or Dess-Martin reagents to give ,-unsaturated ketones, and on treatment withm-chloroperbenzoic acid ortert-butyl hydroperoxide they are oxidized to the corresponding epoxyalcohols. The latter are oxidized by Swern or Dess-Martin reagents at the hydroxyl group to ,-epoxyketones, which form hydrates stable under the conditions of isolation.Translated fromIzvestiya Akadernii Nauk. Seriya Khimicheskaya, No. 3, pp. 680–683, March, 1996.     

“Palladium complexes-KF / alumina” catalysed exchange of allylic groups of esters with phenol

In the presence of KF / alumina and catalytic amounts of palladium complexes, phenol reacts with allylic esters under mild conditions to give the corresponding allyl phenyl ethers.     

Synthesis of α,α-disubstituted aryl amines by rhodium-catalyzed amination of tertiary allylic trichloroacetimidates

The rhodium-catalyzed regioselective amination of tertiary allylic trichloroacetimidates with unactivated aromatic amines is a direct and efficient approach to the preparation of α,α-disubstituted allylic aryl amines in good yield and with excellent regioselectivity. This method is applicable to a variety of unactivated primary and secondary amines and allows for the preparation of reverse prenylated indoles in two steps.     

Visible-light-promoted radical alkylation/cyclization of allylic amide with N-hydroxyphthalimide ester: Synthesis of oxazolines

An efficient photocatalytic alkylation/cyclization of allylic amide with N-hydroxyphthalimide ester has been developed. The transformation is taken advantage of alkyl radicals to attack allylic amide with the assist of inexpensive rose bengal as photocatalyst to prepare a series of alkyl substituted oxazolines in moderate to excellent yields. High regioselectivity, operational safety, mild conditions and excellent substrate generality give this protocol broad application prospects.     

Ir-catalysed formation of C-F bonds. From allylic alcohols to α-fluoroketones

A novel iridium-catalysed tandem isomerisation/C-F bond formation from allylic alcohols and Selectfluor? to prepare α-fluorinated ketones as single constitutional isomers is reported.     

One-pot synthesis of α,β-epoxy ketones by palladium-catalyzed epoxidation-oxidation of terminal allylic alcohols

Described herein is a one-pot synthesis of α,β-epoxy ketones using a palladium-catalyzed epoxidation-oxidation sequence. Functionalized terminal allylic alcohols are treated with m-CPBA under mild reaction conditions to obtain the α,β-epoxy ketones. The main benefit of this approach is that the epoxidation of the terminal double bond and the oxidation of the secondary alcohol occured in the same reaction under mild reactions and both electron-donating and electron-withdrawing functionalities are tolerated in the reaction sequence.     

Rh(Ⅰ)-catalyzed regio-and enantioselective allylic alkylation of Meldrum's acid

A Rh(Ⅰ)-catalyzed highly regio-and enantioselective allylic alkylation of Meldrum acid with racemic allylic substrates bearing alkyl groups has been developed.The applying of chiral bisoxazopinephosphine ligand is essential for the high yields and selectivities.This method provides a rapid access to various chiral β-alkyl-γ,δ-unsaturated carboxylic acids and their derivatives.     

Palladium-catalyzed α-regioselective allylic amination of Morita-Baylis-Hillman acetates with simple aromatic amines

An efficient allylic amination of Morita-Baylis-Hillman acetates with simple aromatic amines provided good yields with excellent α-regioselectivity (up to exclusive α-product) under the catalysis of Pd(2)(dba)(3)/ferrocene-type diphosphine ligand.     

S,O-ligand-promoted palladium-catalyzed C–H olefination of arenes with allylic substrates

An efficient catalytic system for the C–H olefination of arenes with different allylic substrates is reported. The catalytic system is based on Pd(OAc)₂ and a readily accessible bidentate S,O-ligand. The methodology shows high activity with a wide range of arenes, including bulky and, electron-rich and -poor arenes. The applicability of this catalyst is demonstrated in the late-stage functionalization of the complex molecule O-methylestrone.