Lanthanum-Catalyzed Double Hydrophosphinylation of Nitriles

Abstract

A new lanthanum-based catalyst was shown to be effective for the double hydrophosphinylation of unactivated nitriles under very mild conditions. Surprisingly, the lanthanum catalyst gave two regioisomeric products depending on the nature of the starting nitrile. Primary alkyl nitriles undergo 1,1-addition to give products with a new P–C–P linkage and concomitant formation of a primary amine. Under the same conditions, secondary alkyl and aryl nitriles instead produced 1,2-addition products, where 1 equiv of the phosphine oxide was added to the carbon, while a second equivalent added to the nitrogen of the nitrile, resulting in a P–C–N–P framework. Further investigation of the catalytic cycle yielded evidence that all nitriles first undergo 1,1-addition (deemed the kinetic product) that then undergoes isomerization to the final unsymmetric addition product (the thermodynamic product). All catalytic reactions were run neat or with very little solvent, required little workup, and had high to moderate yields.

Alkali Metal Catalysed Double Hydrophosphorylation of Nitriles and Alkynes

“…Scheme describes the most plausible mechanism for the double hydrophosphorylation of ‐C≡N and ‐C≡C‐ groups and diphenylphosphane oxide mediated by alkali metal hexamethyl‐disilazides. This mechanism is based on group 1 and group 3 metal–catalysed hydrophosphorylation of alkynes reported recently by Westerhausen and Schmidt respectively , . In the first step, [KN(SiMe 3 ) 2 ] reacts with diphenylphosphane oxide to give potassium diphenylphosphinite [KP(O)Ph 2 ] ( I ) via the removal of HN(SiMe 3 ) 2 , and [KP(O)Ph 2 ] ( I ) acts as the catalytically active species.…”

“…Supporting information (see footnote on the first page of this article): Data for 3a, 3b, 3d, 3g, 3h, 3i, 3j, 3k and 5a, 5d, 5e, 5f are already described in literature , ,. [20a] Crystallographic data of 3e and 3l and 1 H, 13 C{ 1 H} and 31 P{ 1 H} NMR spectra of bis‐hydrophosphorylated products, 3a – 3o and 5a – 5j are given.…”

“…Storace et al first noted that the formation of P–C–N–P linkage, with low yields of double phosphorylated product, was extremely useful for the human leukocyte elastase inhibitor . Very recently, the lanthanum (III) metal complex was employed by Schmidt et al as an efficient catalyst for the hydrophosphorylation of a wide range of nitriles to obtain both the 1,1 and 1,2‐regioisomers in good yield after extending the reaction times …”

“…[15] Very recently, the lanthanum (III) metal complex was employed by Schmidt et al as an efficient catalyst for the hydrophosphorylation of a wide range of nitriles to obtain both the 1,1 and 1,2-regioisomers in good yield after extending the reaction times. [16] Notably, various reports also describe the utility of carbon-carbon unsaturated systems for the synthesis of organophosphorus compounds mediated by alkali metal catalysts. Several reports have recognised the synthesis of mono-or bisalkenylphosphane oxides.…”

Brønsted Base‐Catalyzed Umpolung Intramolecular Cyclization of Alkynyl Imines

“…[4] As the next stage of our research, we envisioned the development of catalytic carbon-carbon bond-forming reactions involving "umpolung" generation of aaminoc arbanions from imines.I nc ontrast to the original [1,2]phospha-Brook rearrangement, namely the [1,2]-rearrangement from carbon to oxygen, the [1,2]-rearrangement of ad ialkoxyphosphoryl moiety from carbon to nitrogen is very rare and has only been observed in very specific cases. [5] Furthermore, catalytic reactions involving the generation of a-amino carbanions via rearrangement and subsequent transformation, such as carbon-carbon bond formation, have never been developed despite the fact that the originalo xygen version has been well-established and used in severalc atalytic carbon-carbon bond-forming reactions under Brønsted base catalysis. [2,4] Therefore, the establishment of an efficient catalytic system for an unprecedented catalytic "umpolung" generation of carbanions from imines is the key to the development of subsequent catalyticc arbon-carbon bond-forming reactions and hence presentsasignificant challenge.…”