Access to Enantiomerically PureP‐Stereogenic Primary Aminophosphine Sulfides under Reductive Conditions

Abstract

Stereochemically pure phosphines with phosphorus‐heteroatom bonds and P‐centered chirality are a promising class of functional building blocks for the design of chiral ligands and organocatalysts. A route to enantiomerically pure primary aminophosphine sulfides was opened through stereospecific reductive C−N bond cleavage of phosphorus(V) precursors by lithium in liquid ammonia. The chemoselectivity of the reaction as a function of reaction time, substrate pattern, and chiral auxiliary was investigated. In the presence of exclusively aliphatic groups bound to the phosphorus atom, all competing reductive side reactions are totally prevented. The absolute configurations of all P‐stereogenic compounds were determined by single‐crystal X‐ray diffraction analysis. Their use as synthetic building blocks was demonstrated. The lithium salt of (R)‐BINOL‐dithiophosphoric acid proved to be a useful stereochemical probe to determine the enantiomeric purity. Insights into the coordination mode of the lithium‐based chiral complex formed in solution was provided by NMR spectroscopy and DFT calculations.

Stereochemically Pure Si‐Chiral Aminochlorosilanes

“…The enantiomeric ratios of compounds ( S Si )‐ 6 and 8 were determined by our recently reported NMR spectroscopic method using lithiated ( R )‐BINOL‐dithiophosphoric acid [( R )‐BINOL‐PSSLi] as chiral shift reagent (for details, see the Supporting Information) [9] . By applying this method to silanols and silanethiols, we were able to demonstrate that this practical tool can be used to determine the enantiomeric purity of chiral compounds that are sensitive towards Brønsted acids.…”

“…(R)-BINOL-dithiophosphoric acid [(R)-BINOL-PSSH] (99 % ee) was synthesized according to a reported literature procedure. [9,21] tert-Butyldichlorophenylsilane (1) [22] and tertbutyldimethoxyphenylsilane (5) [23] were synthesized according to modified literature procedures. NMR Spectra were recorded in C 6 D 6 (� 99 %, Merck KGaA; dried over 3 Å molecular sieves and degassed by a standard freeze-pump-thaw procedure), CDCl 3 (99.8 %, Sigma-Aldrich; basified with Na 2 CO 3 and dried over 3 Å molecular sieves) or CD 2 Cl 2 (� 99.8 %, Fluorochem; dried over 3 Å molecular sieves and degassed by a standard freeze-pump-thaw procedure).…”

“…n ‐Butyllithium (2.5 M solution in hexane, Merck KGaA), tert ‐butyllithium (1.7 M solution in hexane, Merck KGaA), ( S )‐(−)‐1‐phenylethylamine [( S C )‐ 2 ] (98 %, Merck KGaA), ( S )‐(+)‐3,3‐dimethyl‐2‐butylamine (97 %, Sigma‐Aldrich), hydrogen chloride (2.0 M solution in diethyl ether, Sigma‐Aldrich) hydrogen sulfide (0.8 M solution in tetrahydrofuran, Sigma‐Aldrich), methanol (dried over 3 Å molecular sieves), pyrrolidine (99 %, Sigma‐Aldrich), trichlorophenylsilane (97 %, Alfa Aesar), and triethylamine (99 %, Merck KGaA) were used as received without further purification. ( R )‐BINOL‐dithiophosphoric acid [( R )‐BINOL‐PSSH] (99 % ee) was synthesized according to a reported literature procedure [9,21] . tert ‐Butyldichlorophenylsilane ( 1 ) [22] and tert ‐butyldimethoxyphenylsilane ( 5 ) [23] were synthesized according to modified literature procedures.…”

“…[5b] We recently re-ported the use of this chiral primary amine as an efficient chiral auxiliary in the preparation of enantiomerically pure aminophosphine sulfides featuring phosphorus-centered chirality. [9] In the present work, we describe a facile route to diastereomerically pure silicon-stereogenic aminochlorosilanes. SiÀ NH bond formation between tert-butyldichlorophenylsilane and (S)-(À )-1-phenylethylamine followed by fractional crystallizations allowed complete separation of the two diastereomers of the aminochlorosilane.…”

“…The coupling of ( S )‐(−)‐1‐phenylethylamine with a methoxysilane has been previously described [5b] . We recently reported the use of this chiral primary amine as an efficient chiral auxiliary in the preparation of enantiomerically pure aminophosphine sulfides featuring phosphorus‐centered chirality [9] …”