Furan asymmetric alkylation

In 2004, Terada and coworkers reported the first asymmetric phosphoric acid-catalyzed Friedel-Crafts alkylation (Scheme 8). Aldimines 11 reacted with commercially available 2-methoxy furan (20) in the presence of BINOL phosphate (/ )-3q (2 mol%, R = S.S-MeSj-C Hj) to provide access to A-Boc-protected 2-furyl amines 21 in high yields (80-96%) and enantioselectivities (86-97% ee) [19]. 

Jarosz, S. and Zamojski, A. (1982) Asymmetric photocycloaddition between furan and chiral alkyl glyoxylates. Tetrahedron, 38, 1447-1451. 

Uraguchi D, Sorimachi K, Terada M (2004) Organocatalytic asymmetric aza-Friedel-Crafts alkylation of furan. J Am Chem Soc 126 11804-11805 Uraguchi D, Terada M (2004) Chiral Brpnsted acid-catalyzed direct Mannich reactions via electrophilic activation. J Am Chem Soc 126 5356-5357 Vachal P, Jacobsen EN (2000) Enantioselective catalytic addition of HCN to ketoimines. Catalytic synthesis of quaternary amino acids. Org Lett 2 867-870... 

Friedel-Crafts Alkylation Reactions. The activation of glyoxylate esters,trifluoromethyl pyruvate esters, and unsaturated a-ketoesters by catalyst 2 converts these materials into effective electrophiles for asymmetric Friedel-Crafts alkylation reactions with activated arenes (eqs 16 and 17). In fact, bis(triflate) (2) is far superior to tbe bis(hexafluoroantimonate) complex at catalyzing the enantioselective alkylation of benzene derivatives. Aniline and anisole derivatives both give the reaction, as do heterocyclic aromatic compounds such as indole and furan. 

Phenylmenthol is the auxiliary in an asymmetric Birch reduction of pyrroles by Donohoe37 Lithium in ammonia does the reduction and the enolate is trapped with various alkyl halides. Hydrolysis of the esters 227 releases the enantiomerically enriched (78-90% ee) dihydropyrroles 228 in good yield. Furans give similar products with a C2 symmetric amine as auxiliary. This should become a general route to a variety of heterocycles. 

Most AFC alkylation reactions are focused on relatively reactive furans, pyrroles, and indoles, whereas benzene derivatives are much less explored. The Wang group reported the organocatalytic asymmetric synthesis of chromane and dihydrobenzopyrane derivatives 121 from readily available 1-naphthols and a,p-unsaturated aldehydes by the AFC alkylation/cyclization cascade reaction (Scheme 6.49). The process appeared to have a broad substrate... 

Scheme 2.117 Asymmetric Friedel-Ciafts alkylation of furans with enones...

An intramolecular phosphoric acid-catalyzed asymmetric 5 2-type alkylation reaction of alcohols with racemic secondary benzylic ethers resulted in a catalytic asymmetric transetherification reaction to form benzo[c]furan species via the potential of asymmetric Bronsted acid catalysis for the activation of normally unreactive functional groups such as ethers and potentially other less reactive substrates (13AGE3490). 

For selected pioneering examples, see (a) D. Uraguchi, K. Sorimachi, M. Terada, J. Am. Chem. Soc. 2004, 126, 11804-11805. Organocatalytic asymmetric aza-Friedel-Crafts alkylation of furan. (b) T. Akiyama, H. Morita, J. Itoh, K. Fuchibe, Org. Lett. 2005, 7, 2583-2585. Chiral Br0nsted acid catalyzed enantioselective hydrophosphonylation of imines asymmetric synthesis of a-amino phosphonates. 

An intermolecular asymmetric addition of heteroarenes (indoles, thiophenes, pyrroles, and furans) to bicycloalkenes has been developed (with <99% ee). The reaction is catalysed by the complex generated from [(COD)lrCl]2 (1.5mol%) and (5)-TDBM-SEGPHOS (3 mol%) and proceeds in THF at 100 °C over 24 h via the initial activation of the C-H bond vicinal to the heteroatom (even with unprotected indoles, which typically undergo alkylation at the C(3) position), followed by a iy -addition across the C=C bond.128... 

Asymmetric furans 79a and 79b were prepared as shown in Scheme 14.27 [70]. A one-pot sequence comprising monolithiation of furan (15) and alkylation of the resulting lithiofuran 78 with 1-bromohexane gave 2-hexylfuran (79a) in 43% yield. Then, a second lithiation of 79a followed by reaction of the resulting lithiofuran 80 with acetone and hydrogenolysis of alcohol 81 over Pd/C yielded 2-hexyl-5-isopropylfuran (79b) in 34% three-step yield from 79a. Reaction of 2,6-naphthodiyne equivalent 39 (0.5 equiv) with asymmetric furans 79 in the presence of KF and 18-crown-6 in THF at room temperature furnished a mixture of bis(furan)... 

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