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A new double anionic equivalent of the Friedel–Crafts reaction is observed upon treatment of the carbamoyltriarylphosphane oxide 1 with lithium diisopropylamide (LDA) to produce the phosphacycle 2. The scope of this and related reactions is delineated.

Using the new P(O) t Bu 2 Directed Metalation Group, a variety of ortho-substituted aryl di-t-butylphenylphosphine oxides (2a-k) have been prepared, its relative metalation ability has been established, and reduction and homocoupling products (Scheme 4) have been obtained.In the realm of heteroatom-containing Directed Metalation Groups (DMGs), 3 existing phosphorus-based DMGs (Scheme 1) exhibit limitations of synthetic inaccessibility, ineffective directing ability, and competing side reactions. 4 Of particular note is the diphenylphosphinyl DMG which allows access to important phosphino aryl ligands but is plagued with competing attack at phosphorus. 5 To overcome this limitation, Schmid 6 and Brown 7 implemented a cooperative meta-OMe DMG effect which allows regioselective in-between metalation using tbutyllithium or LDA. Herein we report on the di-t-butylphosphinyl DMG, assign its relative metalating position vis a vis other useful DMGs, and demonstrate its utility for the synthesis of diversely substituted aromatics, including sterically compromised arylphosphines, systems of increasing interest as ligands in organometallic catalysis. 8,9 Scheme 1Di-t-butylphenylphosphine oxide (1) was chosen for metalation studies based on the absence of α-deprotonation sites and the expectation that the hindered P(O) t Bu 2 moiety would serve to minimize P-nucleophilic attack. Furthermore, a calculation (MM2 force field) indicated a proximate oxygen-ortho-H distance (2.3 Å) which, with wellrecognized caveat understood, suggested favorable ortho metalation. 10,11 Substrate 1, readily prepared in good yield by modification of a literature procedure (Scheme 2) 6,12,13 was subjected to metalation with t-butyllithium (1-2 equiv), chosen largely for purposes of degeneracy. The resulting suspension of the yellow ortholithio species was treated with a representative series of electrophiles to give a range of 2-substituted arylphosphinyl derivatives 2a-k (Table 1). 14 Thus, aside from the classical carbon electrophiles (entries 1-5), quenching with B(OMe) 3 followed by oxidation furnished a phosphinyl phenol (entry 7) and treatment with other heteroatom electrophiles led to silicon, phosphorus and halogen arylphosphinyl derivatives (entries 8-11). Treatment of the ortho-P/B substituted aromatic (entry 6) with propanediol (MgSO 4 / CH 2 Cl 2 / rt) afforded the boronate 2f whose Xray structure (Figure 1) 11,15 reveals a strong boron-oxygen interaction (B-O distance = 1.67 Å) and thus a planar P-O-B heterocyclic arrangement with a tetrahedral boron atom. 16 In order to evaluate the relative metalating power of P(O) t Bu 2 in the DMG hierarchy, 3 intra-and inter-molecular competition experiments were performed on substrates 3 -5 (Scheme 3). 17 Using kinetically limiting conditions (t-BuLi / THF / -78°C / 5 min) 18 and TMSCl quench, substrates 3 and 4 underwent exclusive metalation ortho to the phosphinyl and ortho to the amide group respectively ( 1 H NMR analysis, isolated % yields of products are shown). Metalation of 5 afforded the ...

Carbanion-mediated general regioselective routes to acridones 4 (Table 2) and dibenzo[b,f]azepinones 20 (Table 4) are described. Buchwald-Hartwig C-N cross coupling of o-halo benzamides 1 with anilines 2 or 16, followed by simple N-methylation, dependably provides N-methyl diarylamines 3 (Table 1) and 18 (Table 3). Upon treatment with LDA, 3 and 18 are converted into acridones 4 and dibenzo[b,f]azepinones 20, respectively, in good to excellent yields with regioselectivity which depends upon the presence or absence of directed metalation groups (DMGs). Brief investigations as follows are described: the synthesis of desmethyl acridone 15 (Scheme 4), an attempt to effect a double-directed remote metalation sequence which leads only to a monocyclization product 13 (Scheme 3), and an analogous but nonregioselective route to a xanthone 22 and dibenzo[b,f]oxepinone 24 (Scheme 5). DFT calculations reveal low energy conformations for compounds 18b and 23 which account for product formation and indicate that the cyclization reactions are under kinetic control.