Chiral Brønsted acid-catalyzed enantioselective Friedel–Crafts reaction of 2-methoxyfuran with aliphatic ketimines generated in situ

Abstract

An enantioselective Friedel–Crafts reaction with aliphatic ketimines generated in situ from hemiaminal ethers afforded products with high enantioselectivity under the influence of a chiral phosphoric acid catalyst.

Enantioselective Synthesis of 5,5‐Disubstituted Hydantoins by Brønsted Base/H‐Bond Catalyst Assisted Michael Reactions of a Design Template

“…Thus, not only methyl but also benzyl( Ta ble 4, entries 12 and 13) and other alkyl (Table 4, entry 14) and functionalizedc hains (Table4,e ntries 15 and 16) were tolerated at the substrate C 5 position without affecting the reaction efficiency or selectivity.O nthe otherh and, N 3 -aryl substrates 20-24 bearinga ryl groups other than phenyl also Scheme4.Catalyst screening for the reaction of 19 A with nitrostyrene. participated in this reactions atisfactorily (Table 4, entries [17][18][19][20][21]. Vinyl ketones were also competent electrophilic partnersi n the reactions of N 3 -substituted 2-benzylthioimidazolones 19-24.H owever,i nc ontrast to that observed with nitroalkenes, the reactions involving vinyl ketones followed two divergent pathways:o ne producing 5-additionp roducts 40 ando ne producing 3-additionp roducts 40' (Scheme 5).…”

“…Clayden developed an elegant protocol to access quaternary hydantoins and compounds derived thereof with good diastereoselectivity on the basis of a substrate‐controlled anionic aryl group N→C rearrangement on lithiated ureas (Figure a). On the other hand, Terada recently reported a chiral phosphoric acid catalyzed Friedel–Crafts‐type addition of 2‐methoxyfuran to in situ generated ketimines (Figure b) . Despite these significant advances, the scope of available optically active quaternary hydantoins continues to be rather narrow and is essentially restricted to some particular 5‐aryl‐substituted subfamilies.…”

“…On the other hand, Te rada recently reported ac hiral phosphoric acid catalyzed Friedel-Crafts-type addition of 2-methoxyfuran to in situ generated ketimines (Figure 2b). [21] Despite these significant advances, the scope of availableo ptically active quaternary hydantoins continues to be rather narrow and is essentially restrictedt os ome particular5-aryl-substituteds ubfamilies.…”

Organocatalyzed Asymmetric Friedel‐Crafts Reactions: An Update

“…Terada and co‐workers in 2013 established an efficient AF‐C reaction between aliphatic ketamine derivatives containing various alkyl groups with the extension of the scope of the nucleophiles using chiral phosphoric acids (CPA) as a chiral Brønsted acid catalyst . An AF‐CA reaction with aliphatic ketimine derivatives produced spontaneously from hemiaminal ether derivatives mediated using a chiral Brønsted acid has been examined.…”

“…The generality of this reaction has been prolonged through the hydantoin derivatives 102 to the thiohydantoin derivatives 101 . However, the reaction of 102 needed an extended reaction time compared with that of 101 , the desired products 105 have been produced in excellent yields and ee s, excepting for 105 c bearing an isopropyl substituent (Scheme , Table ) …”