Cobalt‐Catalysed Asymmetric Addition and Alkylation of Secondary Phosphine Oxides for the Synthesis of P‐Stereogenic Compounds

Abstract

The catalytic asymmetric synthesis of P-chiral phosphorus compounds is an important way to construct Pchiral ligands. Herein, we report a new strategy that adopts the pyridinyl moiety as the coordinating group in the cobaltcatalysed asymmetric nucleophilic addition/alkylation of secondary phosphine oxides. A series of tertiary phosphine oxides were generated with up to 99 % yield and 99.5 % ee, and with broad functional-group tolerance. Mechanistic studies reveal that (R)-secondary phosphine oxides preferentially interact with the cobalt catalysts to produce P-stereogenic compounds.Chiral phosphorus compounds play important roles as ligands [1] or organic catalysts [2] in asymmetric catalysis. Compared to the synthesis of axial-, planar-, and carboncentered chiral phosphorus compounds, the synthesis of Pstereogenic phosphines has been less investigated. The main recent strategies for the preparation of P-chiral compounds involve the use of chiral auxiliary materials or the resolution of racemates. [3] These classical methods require stoichiometric chiral agents or generate an equivalent amount of compound with an opposite configuration. [4] Recently, several asymmetric catalytic methods were developed based on the desymmetrization of phosphine oxides via CÀH bond activation, [5] asymmetric addition, [6] ring-closing metatheses, [7] and [2+2+2] cycloaddition processes. [8] In addition, secondary phosphines have been used as nucleophiles in asymmetric conjugate addition, [9] alkylation, [10] and arylation reactions. [11] However, in this process, the strong coordination ability of the secondary phosphines may lead to deactivation of the metal catalyst, thereby reducing the enantioselectivity. Therefore, the development of alternative methods for the synthesis of P-chiral compounds is still highly necessary.Compared with secondary phosphines, secondary phosphine oxides (SPOs) are more stable in air and have low toxicity to metal catalysts. Nonetheless, only a few synthetic examples have been reported for the preparation of optically active tertiary phosphine oxides (TPOs) from SPOs. In 2016, Gaunt and co-workers reported a new strategy in which Cu combined with chiral pyridine-2,6-bis(oxazolines) ligand (pybox) was applied for the enantioselective arylation of SPOs with diaryliodonium salt, affording P-chiral tertiary phosphorus compounds with up to 98 % ee (Scheme 1 a). [12] The Cai group reported a Pd-catalysed arylation of SPOs with aryl iodides with moderate to high ee (Scheme 1 b). [13] Recently, Zhang and co-workers also reported Pd-catalysed asymmetric arylation and alkenylation reactions of SPOs (Scheme 1 c), in which products were obtained in up to 99 % ee. [14] In addition to the above examples, the Qing-Wei Zhang group developed a Ni-catalysed kinetic resolution of SPOs via an allylic substitution process, providing a series of Pstereogenic compounds with high enantioselectivity (Scheme 1 d). [15] However, the SPOs in the abovementioned examples usually contain one aryl and one alkyl group. Substrates b...

Resolution of aryl-H-phosphinates applied in the synthesis of P-stereogenic compounds including a Brønsted acid NMR solvating agent

“…Preparation of enantiomerically enriched P*(O)H compounds using kinetic resolution became a popular method in recent years. Generally, these procedures were optimized to give enantiopure tertiary phosphine oxides, 15 but in a few instances, the remaining >P(O)H starting materials were also obtained with high enantiomeric excess. 16 Secondary phosphine oxides were the main starting materials in these reactions, but a few procedures are also known for H -phosphinates.…”

Ni-catalyzed asymmetric hydrophosphinylation of conjugated enynes and mechanistic studies

“…However, the enantioselective reactions were achieved with limited success. 5 In addition, the control of P -chirality was much more challenging than carbon chiralities as exemplified by Leung’s, 6 Dong’s, 7 Wang’s 8 and Yin's 9 studies, which achieved excellent enantioselectivities of carbon stereocenters but suffered from low d.r. when racemic secondary phosphine oxides were used.…”

Manganese(i)-catalyzed access to 1,2-bisphosphine ligands

“… 4 Following the publication of this initial work, precious noble metal complexes such as chiral Pd or Pt catalysts have been widely used in the field of asymmetric hydrophosphination ( Scheme 1B ). 5 Only few examples utilizing earth-abundant metals such as Ni, 6 Cu 7 and very recently Mn 8 have been reported to date for catalytic asymmetric hydrophosphination. Apart from metal based catalytic systems, examples of asymmetric organocatalytic hydrophosphination reactions were also presented in the literature.…”