Directed metallation of aromatic compounds

The Urea Renaissance

“…[41] Ureas are potent metalation directing groups as a result of their electron-rich carbonyl group and electron-deficient nitrogen atoms; however, until recently [42] they remained largely unused in the regioselective synthesis of aromatic compounds. Double lithiation of highly hindered N,N-dialkyl-N'-aryl ureas allows ortho functionalization of aniline derivatives.…”

Die Harnstoff‐Renaissance

“…[41] Dank ihrer elektronenreichen Carbonylgruppe und den elektronenarmen Stickstoffatomen sind Harnstoffe effiziente diri- Harnstoff in der organischen Chemie Angewandte Chemie gierende Gruppen für die Metallierung. Trotzdem blieben sie bis vor Kurzem [42] in der regioselektiven Arensynthese weitgehend ungenutzt.…”

Carbamate-directed benzylic lithiation for the diastereo- and enantioselective synthesis of diaryl ether atropisomers

“…An aryloxy group is a weak director of metallation [ 20 , 23 ], but in preliminary studies we were able to deprotonate and methylate the hindered diaryl ether 6 [ 10 ] by treatment with n -BuLi in ether at 0 °C with or without (−)-sparteine ( Scheme 2 ). Methylation of the resulting organolithium returned the product 7 in up to 88% yield as a mixture of diastereoisomers (by NMR).…”

“…The mechanistic possibilities associated with dynamic resolution were initially elaborated by Beak for organolithium compounds having varying degrees of configurational stability [ 17 – 18 ], and in our studies on ureas and amides we were able to identify correlated inversion processes linking configurational inversion at organolithium centres with conformational inversion of atropisomeric chirality by bond rotation [ 19 ]. Several of the classes of atropisomers we have studied contain functional groups which are excellent directors of lithiation [ 20 ], and indeed our original interest in lithiation stemmed from the need to build these atropisomeric structures rapidly and efficiently [ 21 ].…”