Practical Metal‐Free C(sp³)H Functionalization: Construction of Structurally Diverse α‐Substituted N‐Benzyl and N‐Allyl Carbamates

Abstract

Described is a practical and universal CH functionalization of readily removable N‐benzyl and N‐allyl carbamates, with a wide range of nucleophiles at ambient temperature promoted by Ph3CClO4. The metal‐free reaction has an excellent functional‐group tolerance, and displays a broad scope with respect to both N‐carbamates and nucleophile partners (a variety of organoboranes and CH compounds). The synthetic utility in target‐ as well as diversity‐oriented syntheses is demonstrated.

Ultrasounds in Melted Poly(ethylene glycol) Promote Copper‐Catalyzed Cyanation of Aryl Halides with K4[Fe(CN)6]

“…Glycine derivatives 1a – 1n were synthesized according to the known procedures 3b,5. Organoboranes 5 were prepared according to the known literature 11h…”

Recent advance in direct sp3 carbon-hydrogen bond functionalizations

“…The process formed two new C-C bonds through a sequential functionalization of Csp 3 -H/ Csp 2 -H bond giving the corresponding products in up to 86% yield under metal-free conditions. Liu and coworkers [67] reported an efficient Ph3CClO4-promoted Csp 3 -H functionalization for the construction of various α-substituted Nbenzyl and N-allyl carbamates under ambient temperature and metal-free condition (Scheme 60). The approach showed excellent functional-group tolerance with respect to both Ncarbamates and nucleophile partners offering the resulting products with moderate to excellent yields.…”

Selective N-alkylation/α-arylation of N-heterocycles

“…In the case of 30b, the removal was achieved by MW heating at 250 °C in ethyleneglycol for 30 s. 38 When Cbz-protected 1,2,3,4-tetrahydroisoquinoline was applied as starting compound, the desired product (31) could be isolated in only moderate yields. 38,45,47,48 The best yield (69%) was reported by Lou et al when triphenylcarbenium perchlorate (Ph3CClO4) was used as catalyst. 48…”

“…To extend this mMR, 1-naphthol(50) was reacted with 1,2,3,4-tetrahydroisoquinoline(48) in the presence of benzaldehyde, where the possible products obtained by α-arylation/N-alkylation of 48 were 54 and 55 (Scheme 10). For a systematic study of this reaction, the N-alkylated product 2-(2-benzyl-1,2,3,4-tetrahydroisoquinolin-1-yl)naphthalen-1-ol (55) was synthesized from 2-(1,2,3,4-tetrahydroisoquinolin-1-yl)naphthalen-1-ol (56) 12 and benzyl bromide.…”