O-Phosphination of Aldehydes/Ketones toward Phosphoric Esters: Experimental and Mechanistic Studies

Abstract

Addition of P–H species to carbonyl groups, namely the Pudovik reaction, normally delivers hydroxyl phosphorus compounds, along with phosphate byproducts in some cases. A few controllable systems starting from phosphites were set up to mainly provide the phosphates. Herein, we present a highly selective protocol starting from phosphonate precursors leading to phosphinate derivatives. Enantioenriched phosphinates were successfully achieved from chiral phosphine oxide precursors. Experimental and theoretical investigations were conducted to understand the mechanistic details.

Phosphirenium Ions as Masked Phosphenium Catalysts: Mechanistic Evaluation and Application in Synthesis

“…Calculations indicate that loss of {Ph 2 P + } from the parent phosphirenium is uphill by 34 kcal/mol; thus, observation of the free species is unlikely, lending further support to it being transferred directly between nucleophiles during the cycle. Catalytic reactions do show the presence of a phosphinate peak in the 31 P NMR spectrum (−36.5 ppm, corresponding to benzhydryl diphenyl phosphinate), which gives tentative support for the presence of phosphenium adducts.…”

“…Due to the practicality of the reaction, Hirano and Miura's procedure (where the phosphirenium ion was detected but not isolated) 9,11,15 was employed for the synthesis of phosphirenium ion 3•OTf (Table 1, entry 1). Formation of 3• OTf is observed by following the reaction via 31 P{ 1 H} NMR spectroscopy, where a characteristic peak at −108.3 ppm is obtained. 9 To optimize the protocol, different activating agents were reacted with diphenyl acetylene 1 and secondary phosphine oxide (SPO) 2 in CDCl 3 .…”

“…For example, using Cy 2 P(O)H, 4•OTf and 4•B Ar F are isolated in high yields (97 and 98%, respectively). These species display downfield 31 P{ 1 H} NMR signals compared to 3, with a singlet at −85.4 and −86.5 ppm, respectively, due to the increased electron donation of the alkyl substituents. There is only a very modest difference in the 31 Varying the alkyne was also explored; phenyl acetylene and Cy 2 P(O)H lead to full conversion to 7•OTf with a phosphorus signal at −80.2 ppm and a downfield signal for the terminal C−H at 8.4 ppm.…”

Palladium/Xiao‐Phos‐Catalyzed Kinetic Resolution of sec‐Phosphine Oxides by P‐Benzylation

“…Subsequent efforts were turned back to examine other benzylation reagents with more labile nucleofuges. To this end, the easily prepared benzyl diethyl phosphate ( 2 a ) [19] was studied. Gratifyingly, this change led to a dramatic increase in the yield (>40 %) of 3 aa with good enantioselectivity when combined with Cs 2 CO 3 or Rb 2 CO 3 as the base (Table 1, entries 15–16).…”

Palladium/Xiao‐Phos‐Catalyzed Kinetic Resolution of sec‐Phosphine Oxides by P‐Benzylation

“…Subsequent efforts were turned back to examine other benzylation reagents with more labile nucleofuges. To this end, the easily prepared benzyl diethyl phosphate (2 a) [19] was studied. Gratifyingly, this change led to a dramatic increase in the yield (> 40 %) of 3 aa with good enantioselectivity when combined with Cs 2 CO 3 or Rb 2 CO 3 as the base (Table 1, entries [15][16].…”