Kamalraj V. Rajendran

Identification of a key intermediate in the asymmetric Appel process: one pot stereoselective synthesis of P-stereogenic phosphines and phosphine boranes from racemic phosphine oxides

Sequential treatment of racemic phosphine oxides with oxalyl chloride and chiral non-racemic alcohol generates the same ratios of diastereomeric alkoxyphosphonium salts obtained in the corresponding asymmetric Appel process, strongly implicating the intermediate chlorophosphonium salt in the stereoselecting step. Subsequent reduction allows a novel synthesis of enantioenriched P-stereogenic phosphines-phosphine boranes.

Turning Regioselectivity into Stereoselectivity: Efficient Dual Resolution of P‐Stereogenic Phosphine Oxides through Bifurcation of the Reaction Pathway of a Common Intermediate

Synthetic routes that provide facile access to either enantiomeric form of a target compound are particularly valuable. The crystallization-free dual resolution of phosphine oxides that gives highly enantioenriched materials (up to 94 % ee) in excellent yields is reported. Both enantiomeric oxides have been prepared from a single intermediate, (RP )-alkoxyphosphonium chloride, which is formed in the course of a selective dynamic kinetic resolution using a single enantiomer of menthol as the chiral auxiliary. The origin of the dual stereoselectivity lies in bifurcation of the reaction pathway of this intermediate, which works as a stereochemical railroad switch. Under controlled conditions, Arbuzov-type collapse of this intermediate proceeds through CO bond fission with retention of the configuration at the phosphorus center. Conversely, alkaline hydrolysis of the PO bond leads to the opposite SP  enantiomer.

Cleavage of PO in the Presence of P–N: Aminophosphine Oxide Reduction with In Situ Boronation of the PIII Product

In contrast to tertiary phosphine oxides, the deoxygenation of aminophosphine oxides is effectively impossible due to the need to break the immensely strong and inert PO bond in the presence of a relatively weak and more reactive PN bond. This long-standing problem in organophosphorus synthesis is solved by use of oxalyl chloride, which chemoselectively cleaves the PO bond forming a chlorophosphonium salt, leaving the PN bond(s) intact. Subsequent reduction of the chlorophosphonium salt with sodium borohydride forms the P(III) aminophosphine borane adduct. This simple one-pot procedure was applied with good yields for a wide range of PN-containing phosphoryl compounds. The borane product can be easily deprotected to produce the free P(III) aminophosphine. Along with no observed PN bond cleavage, the use of sodium borohydride also permits the presence of ester functional groups in the substrate. The availability of this methodology opens up previously unavailable synthetic options in organophosphorus chemistry, two of which are exemplified.

Hammond Postulate Mirroring Enables Enantiomeric Enrichment of Phosphorus Compounds via Two Thermodynamically Interconnected Sequential Stereoselective Processes.

The dynamic resolution of tertiary phosphines and phosphine oxides was monitored by NMR spectroscopy. It was found that the stereoselectivity is set during the formation of the diastereomeric alkoxyphosphonium salts (DAPS), such that their initial diastereomeric excess (de) limits the final enantiomeric excess (ee) of any phosphorus products derived from them. However, (31)P NMR monitoring of the spontaneous thermal decomposition of the DAPS shows consistent diastereomeric self-enrichment, indicating a higher rate constant for decomposition of the minor diastereomer. This crucial observation was confirmed by reductive trapping of the unreacted enriched DAPS with lithium tri-sec-butylborohydride (commercially distributed as L-Selectride reagent) at different time intervals after the start of reaction, which gives progressively higher ee of the phosphine product with time. It is proposed that the Hammond postulate operates for both formation and decomposition of DAPS intermediate so that the lower rate of formation and faster subsequent collapse of the minor isomer are thermodynamically linked. This kinetic enhancement of kinetic resolution furnishes up to 97% ee product.