Directedortho-Metalation and Anionicortho-Fries Rearrangement of Polycyclic AromaticO-Carbamates: Regioselective Synthesis of Substituted Chrysenes

Abstract

A general method for the regioselective synthesis of a series of ortho-substituted chrysenyl N, N-diethyl- O-carbamates by the directed ortho-metalation (D oM) strategy is reported. The starting O-carbamates were prepared from the corresponding chrysenols, available by oxidative photochemical cyclization or directed remote metalation tactics. Chrysen-1-yl and chrysene-3-yl ring site selectivity of directed ortho-metalation (D oM) and anionic ortho-Fries rearrangement (A oF) protocols, with s-BuLi/TMEDA, followed by electrophilic quench using a selection of electrophiles, were observed, leading to new chrysenyl derivatives. 5-Chrysenyl N,N-diethyl- O-carbamate underwent instant A oF rearrangement even at -100 °C to furnish chrysenyl o-hydroxycarboxamide. Iterative D oM reactions were carried out to gain insight into the regioselectivity factors.

Synthesis of Phenacene–Helicene Hybrids by Directed Remote Metalation

“…This was unanticipated as similar bromination on chrysenes with the N , N -diethylcarbamate directing group was reported in good yields. 60 Thereafter, I 2 was used as an electrophile; besides, iodo substrates are more reactive in the Suzuki–Miyaura cross-coupling. N , N -diethyl-2-iodochrysene-1-carboxamide ( 2a ) was obtained from 1a in excellent yield using s -BuLi/TMEDA and 1 M I 2 in THF ( Scheme 3 a).…”

“…It is worth mentioning, in this context, that our previous D o M study on chrysene-3-yl N , N -diethyl- O -carbamate with s -BuLi/TMEDA afforded only the C2-iodination product regioselectively in excellent yield. 60 In D o M reactions, s -BuLi (p K a = 51) and LiTMP (p K a = 37.3) 65 are the most commonly used bases. 66 In the present work, they were chosen over LDA (p K a = 35.7) 67 based on their base strength, for the previous studies reported p K a > 37.2 for ortho C–H bonds in monosubstituted benzenes with strong DMGs.…”

“…Apparently, 5j is deprotonated on the ring instead of on the methyl group during the DreM reaction, explaining the formation of fluorenone ( Scheme 2 c). 60 …”

“… 59 An attempt to make chrysene from 1-methylnaphthalen-2-yl benzamide gave a fluorenone instead ( Scheme 2 c). 60 Fluorenones are usually formed only in the absence of an ortho (peri)-methyl group in the biaryls. 58 These intriguing results in the presence of three regioisomers of the methylnaphthalenyl moiety inspired us to do a systematic exploration of the DreM reaction on methylnaphthalenyl-containing biaryl derivatives to make larger PAHs.…”

Experimental and Computational Study of the 1,5-O → N Carbamoyl Snieckus–Fries-Type Rearrangement

“…The metalation of arenes bearing an appropriate directing metalation group (DMG) with organolithiums or lithium amides, known as ortho-lithiation, nicely complements the classical electrophilic aromatic substitution, as well as other transition-metal-based methodologies mainly related with C–H activation reactions, for making regiospecifically functionalized aromatic rings. Among the oxygen-based DMGs employed for the functionalization of phenols, O -aryl carbamates have been recognized arguably as one of the most powerful DMGs, and usefully leading to phenol derivatives, with many applications in the synthesis of complex molecules . In addition, the carbamate group could undergo subsequent cross-coupling reactions under transition-metal catalysis …”