The Tetraethylphosphorodiamidate (OP(O)(NEt₂)₂) Directed Metalation Group (DMG). Directedorthoand Lateral Metalation and the Phospha Anionic Fries Rearrangement

Abstract

We report on the tetraethylphosphorodiamidate (−OP­(O)­(NEt2)2) group as an effective directed metalation group (DMG). Lithiation-electrophile quench of 1 provides a general synthesis of ortho-substituted aryl and naphthyl phosphorodiamidates 4–8. We also describe the phospha anionic ortho-Fries (AoF) rearrangement of the phosphorodiamidates 1a,1b → 2 or 3 and its vinylogous counterpart to the ortho-tolyl phosphorodiamidates 5b → 13. Intermolecular competition experiments demonstrate the approximately equal DMG strength of the −OP­(O)­(NEt2)2 and the most powerful OCONEt2 groups.

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 …”

Tetraethylphosphorodiamidate-Directed Metalation Group: Directed Ortho and Remote Metalation, Cross Coupling, and Remote Phospha Anionic Fries Rearrangement Reactions

“…With the series of biaryls 10 in hand, we were in a position to explore the DreM competence of the O PO­(NEt 2 ) 2 DMG. As for the case of the lateral phospha A o F rearrangement, DreM reactions of the phosphorodiamidate and phosphate groups have not, to the best of our knowledge, been described …”

“…In our previous paper, we reported on the directed ortho metalation (D o M) chemistry of the aryl O -tetraethylphosphorodiamidate ( O P­(O)­(NEt 2 ) 2 ) directed metalation group (DMG) and delineated its scope (Figure , 1a ), its anionic ortho Fries rearrangement (A o F, 1b ), and its position in the ortho -metalation hierarchy (OCONR 2 ≥ O P­(O)­(NEt 2 ) 2 ) . Therein, we also evaluated the lateral metalation reaction of the ortho -tolyl O P­(O)­(NEt 2 ) 2 system ( 1c ) and its previously unobserved vinylogous anionic Fries rearrangement ( 1d ) …”

“…To initiate the study, the availability of the o -iodo and o -boronato aryl O -tetraethylphosphorodiamidate 3 from our sequel study allowed their examination as cross coupling partners. In the event, a number of biaryls 4 were synthesized via the Suzuki–Miyaura cross-coupling reaction of o -iodo aryl phosphorodiamidates 3a (X = I) with a variety of commercial aryl boronic acids, furnishing the biaryls 4a – g , j – m in good to excellent yields (Scheme ).…”

α-Lithiobenzyloxy as a Directed Metalation Group inortho-Lithiation Reactions

“…An interesting variation in this chemistry is the one in which the DMG could be a versatile functional group for subsequent manipulations, or the DMG itself could be considered a useful functional group . Thus, one of the main research efforts in the field has been devoted to the discovery of new DMGs …”