The Di-t-Butylphosphinyl Directed ortho Metalation Group. Synthesis of Hindered Dialkylarylphosphines

Abstract

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 ...

Reactions of phosphinites with oxide surfaces: a new method for anchoring organic and organometallic complexes

“…The syntheses of phosphinite compounds and the iridiumpincer complexes were reported previously. 4 Bis(tert-butyl)phenylphosphine oxide was prepared from di-tert-butylchlorophosphine (Strem, 96%), as described by Gray et al 11 A solution-state 31 P{ 1 H} NMR spectrum in CDCl 3 confirmed its identity (d = 51.7 ppm, s). Di-tert-butylphosphine oxide was purchased from Strem, and used as received.…”

“…1) resembles that of an aryl(di-tert-butyl)phosphine oxide. 11 We considered the possibility that arylphosphinites undergo g-alumina-induced rearrangement to the corresponding arylphosphine oxides, which can then interact with g-alumina via the P O moiety through either adsorption onto Lewis acidic Al sites or hydrogen bonding to surface hydroxyl groups.…”

Synthesis of 2-Diphenylphosphinoyl-2-Halo Biphenyls Via Suzuki-Miyaura Coupling as Possible Route to Non-Symmetric Biphenyl Phosphines

“…However these reactions could only achieve monophosphine ligands. The synthesis of 2,2'-biphenyl phosphines has relied on the Ulmann coupling of ortho-iodobenzene derivatives with the limitation of being able to synthesize only symmetric phosphine ligands [6,13,14]. In this context, 2-diphenylphosphinoyl-2'-halogenated biphenyls could open a new route for the preparation of symmetric and non-symmetric 2,2'-biphenylbased bisphosphines.…”

Towards High‐Performance Lewis Acid Organocatalysis

“…[21] Apart from this particular study, the concept of lithiation by means of directed ortho-metalation (DoM) followed by alkylation for the synthesis of new chiral organocatalysts was not further examined, although the orthodirecting properties of, for example, SO 2 NR 2 and P(O)(tBu) 2 groups are well known. [22] We found that (biaryl)hydroxyl acids (HYDRAs) can be synthesized directly from the corresponding unsubstituted disulfonimides. [23] The previously unknown compounds, for example diol 1 a, were accessed in a one-pot lithiation/alkylation sequence with bis[3,5-bis(trifluoromethyl)phenyl]methanone as an electrophile (Scheme 1).…”