Synthesis and Structure of Intermediates in Copper-Catalyzed Alkylation of Diphenylphosphine Matthew F. Cain Russell P. Hughes David S. Glueck James A. Golen Curtis E. Moore Arnold L. Rheingold 10.1021/ic100816u.s001 https://acs.figshare.com/articles/journal_contribution/Synthesis_and_Structure_of_Intermediates_in_Copper_Catalyzed_Alkylation_of_Diphenylphosphine/2734567 Cu(I) catalysts for alkylation of diphenylphosphine were developed. Treatment of [Cu(NCMe)<sub>4</sub>][PF<sub>6</sub>] (<b>1</b>) with chelating ligands gave [CuL(NCMe)][PF<sub>6</sub>] (<b>2</b>; L = MeC(CH<sub>2</sub>PPh<sub>2</sub>)<sub>3</sub> (triphos), <b>3</b>; L = 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (XantPhos)). These complexes catalyzed the alkylation of PHPh<sub>2</sub> with PhCH<sub>2</sub>Br in the presence of the base NaOSiMe<sub>3</sub> to yield PPh<sub>2</sub>CH<sub>2</sub>Ph (<b>4</b>). The precursors Cu(dtbp)(X) (dtbp =2,9-di-<i>t</i>-butylphenanthroline, X = Cl (<b>5</b>) or OTf (<b>6</b>)), CuCl, and <b>1</b> also catalyzed this reaction, but dtbp dissociated from <b>5</b> and <b>6</b> during catalysis. Both <b>2</b> and <b>3</b> also catalyzed alkylation of PHPh<sub>2</sub> with PhCH<sub>2</sub>Cl/NaOSiMe<sub>3</sub>, but XantPhos dissociation was observed when <b>3</b> was used. When CH<sub>2</sub>Cl<sub>2</sub> was used as the solvent for alkylation of PhCH<sub>2</sub>Cl with precursors <b>2</b> or <b>3</b>, or of PhCH(Me)Br with <b>2</b>, it was competitively alkylated to yield PPh<sub>2</sub>CH<sub>2</sub>Cl (<b>7</b>), which was formed exclusively using <b>2</b> in the absence of a benzyl halide. Cu(triphos)-catalyzed alkylation of PhCH(Me)Br gave mostly PPh<sub>2</sub>CHMePh (<b>8</b>), along with some Ph<sub>2</sub>P-PPh<sub>2</sub> (<b>9</b>), which was also formed in attempted alkylation of dibromoethane with this catalyst. The phosphine complexes [Cu(triphos)(L′)][PF<sub>6</sub>] (L′ = PH<sub>2</sub>Ph (<b>10</b>), PH<sub>2</sub>CH<sub>2</sub>Fc (Fc = C<sub>5</sub>H<sub>4</sub>FeC<sub>5</sub>H<sub>5</sub>, <b>11</b>), PHPh<sub>2</sub> (<b>12</b>), PHEt<sub>2</sub> (<b>13</b>), PHCy<sub>2</sub> (Cy = <i>cyclo</i>-C<sub>6</sub>H<sub>11</sub>, <b>14</b>), PHMe(Is) (Is = 2,4,6-(<i>i</i>-Pr)<sub>3</sub>C<sub>6</sub>H<sub>2</sub>, <b>15</b>), PPh<sub>2</sub>CH<sub>2</sub>Ph (<b>16</b>), PPh<sub>2</sub>CH<sub>2</sub>Cl (<b>17</b>)), and [Cu(XantPhos)(L′)][PF<sub>6</sub>] (L′ = PHPh<sub>2</sub> <b>(18</b>), PPh<sub>2</sub>CH<sub>2</sub>Ph (<b>19</b>)) were prepared by treatment of <b>2</b> and <b>3</b> with appropriate ligands. Similarly, treatment of dtbp complexes <b>5</b> or <b>6</b> with PHPh<sub>2</sub> gave [Cu(dtbp)(PHPh<sub>2</sub>)(X)] (X = OTf (<b>20a</b>) or Cl (<b>20b</b>)), and reaction of PPh<sub>2</sub>CH<sub>2</sub>Ph (<b>4</b>) with <b>1</b> formed [Cu(PPh<sub>2</sub>CH<sub>2</sub>Ph)<sub>3</sub>][PF<sub>6</sub>] (<b>21</b>). Complexes <b>2</b>, <b>3</b>, <b>11</b>−<b>14</b>, <b>16</b>, <b>17</b>, <b>19</b>, and <b>21</b> were structurally characterized by X-ray crystallography. Deprotonation of diphenylphosphine complex <b>12</b> in the presence of benzyl bromide gave diphenylbenzylphosphine complex <b>16</b>, while deprotonation of <b>12</b> in CD<sub>2</sub>Cl<sub>2</sub> gave <b>17</b> containing a PPh<sub>2</sub>CD<sub>2</sub>Cl ligand. Low-temperature deprotonation of the soluble salt <b>12</b>-[B(Ar<sub>F</sub>)<sub>4</sub>] (Ar<sub>F</sub> = 3,5-(CF<sub>3</sub>)<sub>2</sub>C<sub>6</sub>H<sub>3</sub>) in THF-d<sub>8</sub> gave the phosphido complex Cu(triphos)(PPh<sub>2</sub>) (<b>22</b>). Thermally unstable <b>22</b> was characterized by NMR spectroscopy and, in comparison to <b>12</b>, by density functional theory (DFT) calculations, which showed it contained a polarized Cu−P bond. The ligand substitution step required for catalytic turnover was observed on treatment of <b>16</b> or <b>17</b> with PHPh<sub>2</sub> to yield equilibrium mixtures containing <b>12</b> and the tertiary phosphines <b>4</b> or <b>7</b>; equilibrium constants for these reactions were 8(2) and 7(2), favoring complexation of the smaller secondary phosphine in both cases. These observations are consistent with a proposed mechanism for catalytic P−C bond formation involving deprotonation of the cationic diphenylphosphine complex [Cu(triphos)(PHPh<sub>2</sub>)][PF<sub>6</sub>] (<b>12</b>) by NaOSiMe<sub>3</sub> to yield the phosphido complex Cu(triphos)(PPh<sub>2</sub>) (<b>22</b>). Nucleophilic attack on the substrate (benzyl halide or CH<sub>2</sub>Cl<sub>2</sub>) then yields the tertiary phosphine complex [Cu(triphos)(PPh<sub>2</sub>CH<sub>2</sub>X)][PF<sub>6</sub>] (X = Ph (<b>16</b>) or Cl (<b>17</b>)), and ligand substitution with PHPh<sub>2</sub> regenerates <b>12</b>. 2010-09-06 00:00:00 5H base NaOSiMe 3 alkylation 2P dtbp complexes 5 PhCH 2Cl NMR 6H 2CH benzyl halide Cu CH 2Cl ligand substitution step DFT CF PHPh 2 PPh 2CD ligand