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A Review of New Developments in the Friedel-Crafts Alkylation - From Green Chemistry to Asymmetric Catalysis

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A Review of New Developments in the Friedel-Crafts Alkylation - From Green Chemistry to Asymmetric Catalysis

Magnus Rueping et al. Beilstein J Org Chem.

Abstract

The development of efficient Friedel-Crafts alkylations of arenes and heteroarenes using only catalytic amounts of a Lewis acid has gained much attention over the last decade. The new catalytic approaches described in this review are favoured over classical Friedel-Crafts conditions as benzyl-, propargyl- and allyl alcohols, or styrenes, can be used instead of toxic benzyl halides. Additionally, only low catalyst loadings are needed to provide a wide range of products. Following a short introduction about the origin and classical definition of the Friedel-Crafts reaction, the review will describe the different environmentally benign substrates which can be applied today as an approach towards greener processes. Additionally, the first diastereoselective and enantioselective Friedel-Crafts-type alkylations will be highlighted.

Keywords: Friedel–Crafts alkylation; Lewis-acid catalysis; allyl alcohols; arene; asymmetric Friedel–Crafts reaction; benzyl alcohols; green chemistry; hydroalkylation; hydroarylation; propargyl alcohols.

Figures

Scheme 1
Scheme 1
AlCl3-mediated reaction between amyl chloride and benzene as developed by Friedel and Crafts.
Figure 1
Figure 1
Most often used metal salts for catalytic FC alkylations and hydroarylations of arenes.
Figure 2
Figure 2
1,1-diarylalkanes with biological activity.
Scheme 2
Scheme 2
Alkylating reagents and side products produced.
Scheme 3
Scheme 3
Initially reported TeCl4-mediated FC alkylation of 1-penylethanol with toluene.
Scheme 4
Scheme 4
Sc(OTf)3-catalyzed FC benzylation of arenes.
Scheme 5
Scheme 5
Reductive FC alkylation of arenes with arenecarbaldehydes.
Scheme 6
Scheme 6
Iron(III)-catalyzed FC benzylation of arenes and heteroarenes.
Scheme 7
Scheme 7
A gold(III)-catalyzed route to beclobrate.
Scheme 8
Scheme 8
Catalytic FC-type alkylations of 1,3-dicarbonyl compounds.
Scheme 9
Scheme 9
Iron(III)-catalyzed synthesis of phenprocoumon.
Scheme 10
Scheme 10
Bi(OTf)3-catalyzed FC alkylation of benzyl alcohols developed by Rueping et al.
Scheme 11
Scheme 11
(A) Bi(OTf)3-catalyzed intramolecular FC alkylation as an efficient route to substituted fulvenes. (B) Nanostructured MoO3 mediated intramolecular FC alkylation.
Scheme 12
Scheme 12
FC-type glycosylation of 1,2-dimethylindole and trimethoxybenzene.
Scheme 13
Scheme 13
FC alkylation with highly reactive ferrocenyl- and benzyl alcohols. The reaction proceeds even without Lewis acids just “on water”.
Scheme 14
Scheme 14
Reductive FC alkylation of arenes with benzaldehyde and acetophenone catalyzed by the Ir-carbene complex 33.
Scheme 15
Scheme 15
Formal synthesis of 1,1-diarylalkanes from benzyl alcohols and styrenes.
Scheme 16
Scheme 16
(A) Mo-catalyzed hydroarylation of styrenes and cyclohexenes. (B) Hydroalkylation–cyclization cascade leading to 1,1-diarylalkane 38 from the linear precursor citral (37).
Scheme 17
Scheme 17
Bi(III)-catalyzed hydroarylation of styrenes with arenes and heteroarenes.
Scheme 18
Scheme 18
BiCl3-catalyzed ene/FC alkylation reaction cascade – A fast access to highly arylated dihydroindenes.
Scheme 19
Scheme 19
Au(I)/Ag(I)-catalyzed hydroarylation of indoles with styrenes, aliphatic and cyclic alkenes.
Scheme 20
Scheme 20
First transition-metal-catalyzed ortho-hydroarylation developed by Beller et al.
Scheme 21
Scheme 21
(A) Ti(IV)-mediated rearrangement of an N-benzylated aniline to the corresponding ortho-alkylated aniline. (B) ortho-Arylation of anilines with styrenes in the presence of TiCl4.
Scheme 22
Scheme 22
Dibenzylation of aniline gives potentially useful amine-based ligands in a one-step procedure.
Scheme 23
Scheme 23
FC-type alkylations with allyl alcohols as alkylating reagents – linear vs. branched product formation.
Scheme 24
Scheme 24
(A) First catalytic FC allylation and cinnamylation using allyl alcohols and its derivatives. (B) Efficient Mo-catalyzed synthesis of methyleugenol.
Scheme 25
Scheme 25
FC allylation/cyclization reaction yielding substituted chromanes.
Scheme 26
Scheme 26
Synthesis of (all-rac)-α-tocopherol utilizing Lewis- and strong Brønsted-acids.
Scheme 27
Scheme 27
Au(III)-catalyzed cinnamylation of arenes.
Scheme 28
Scheme 28
“Exhaustive” allylation of benzene-1,3,5-triol.
Scheme 29
Scheme 29
Palladium-catalyzed allylation of indole.
Scheme 30
Scheme 30
Pd-catalyzed synthesis of pyrroloindoles from L-tryptophane.
Scheme 31
Scheme 31
Ru(IV)-catalyzed allylation of indole and pyrroles with unique regioselectivity.
Scheme 32
Scheme 32
Silver(I)-catalyzed intramolecular FC-type allylation of arenes and heteroarenes.
Scheme 33
Scheme 33
FC-type alkylations of arenes using propargyl alcohols.
Scheme 34
Scheme 34
(A) Propargylation of arenes with stoichiometric amounts of the Ru-allenylidene complex 86. (B) First catalytic propargylation of (hetero)arenes using a cationic Ru-complex.
Scheme 35
Scheme 35
Diruthenium-catalyzed formation of chromenes and 1H-naphtho[2,1-b]pyrans.
Scheme 36
Scheme 36
Rhenium(V)-catalyzed FC propargylations as a first step in the total synthesis of podophyllotoxin, mimosifoliol and O-methyldetrol.
Scheme 37
Scheme 37
Scandium-catalyzed arylation of 3-sulfanyl- and 3-selanylpropargyl alcohols.
Scheme 38
Scheme 38
Synthesis of 1,3-diarylpropynes via direct coupling of propargyl trichloracetimidates and arenes.
Scheme 39
Scheme 39
Diastereoselective substitutions of benzyl alcohols.
Scheme 40
Scheme 40
(A) First diastereoselective FC alkylations developed by Bach et al. (B) anti-Selective FC alkylation of α-phenyl substituted benzyl alcohols.
Scheme 41
Scheme 41
Diastereoselective AuCl3-catalyzed FC alkylation.
Scheme 42
Scheme 42
Bi(OTf)3-catalyzed alkylation of α-chiral benzyl acetates with silyl enol ethers.
Scheme 43
Scheme 43
Bi(OTf)3-catalyzed diastereoselective substitution of propargyl acetates.
Scheme 44
Scheme 44
Nucelophilic substitution of enantioenriched ferrocenyl alcohols.
Scheme 45
Scheme 45
First catalytic enantioselective propargylation of arenes.

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