Synthesis of a New Chiral Cyclico-Hydroxynaphthylphosphonodiamide and its Application as Ligand Catalyst in Asymmetric Silylcyanation of Aromatic Aldehydes

Abstract

A new chiral cyclic o-hydroxynaphthylphosphonodiamide (+)-2 was synthesized starting from (+)-cis-1,2,2-trimethylcyclopentane-1,3-diamine. The absolute configuration of phosphorus atom was determined as S by X-ray diffraction analysis. Excellent enantioselectivity (up to 98.3% ee) was achieved in asymmetric silylcyanation of aromatic aldehydes using a chiral titanium complex prepared in situ from Ti(Oi-Pr) 4 and (+)-2 as the catalyst.Optically active cyanohydrins are important intermediates in organic synthesis for the synthesis of a variety of valuable classes of chiral compounds, such as a-amino acids, a-hydroxyl carboxylic acids, b-amino alcohols, vicinal diols, a-hydroxyketones, etc. Many efficient approaches have been reported for obtaining them by biochemical and chemical methods. 1 In the latter, the most important one was the asymmetric silylcyanation of aldehydes with trimethylsilylcyanide catalyzed by a Lewis acid, such as Ti(Oi-Pr) 4 , TiCl 4 , AlCl 3 , SmCl 3 , etc. in the presence of a chiral ligand. In this reaction, a wide range of chiral ligands have been elaborated, such as Schiff bases, 2 diols, 3 diamides, 4 phosphorus compounds, 5 etc. As shown in literature, most of the effective chiral ligands have a free hydroxyl group or an amino group bearing at least a N-H bond which is favorable to coordinate conveniently with the metal atom in Lewis acid. Thus the moiety of the coordinated metal atom should work as a Lewis acid center (LA). Moreover, if a phosphoryl group (P=O) is existed at an appropriate position in the ligand molecule, the unshared electron pair on oxygen atom should act as a Lewis base (LB). In the catalyst, it contains both a Lewis acid center and a Lewis base center, namely, LALB catalyst. It is a new type of chiral bifunctional catalyst. 5b Based on these findings, recently, a new cyclic o-hydroxynaphthylphosphonodiamide (1) was synthesized starting from (-)-a-phenylethylamine and employed in the asymmetric silylcyanation of aromatic aldehydes in the presence of Ti(Oi-Pr) 4 by our research group. The corresponding cyanohydrins were obtained in high chemical yields with good to excellent enantiomeric excesses up to 90%. 6 In order to further improve the enantioselectivity of this type of cyclophosphonodiamides, in this paper, we will report the synthesis of a new cyclic o-hydroxynaphthylphosphonodiamide (2) containing a phosphorus stereocenter starting from (+)-cis-1,2,2-trimethylcyclopentane-1,3-diamine (3) and its application in asymmetric silylcyanation of aromatic aldehydes (Figure 1, Scheme 1). Scheme 1NH 2 NH 2

o‐Hydroxyarylphosphanes: Strategies for Syntheses of Configurationally Stable, Electronically and Sterically Tunable Ambiphiles with Multiple Applications

“…In this connection it shall be noted that treatment of the C‐analogous O ‐arylcarbamates with s BuLi (−78 °C) also leads to 1,3‐O,C‐rearrangement whereas reaction with s BuLi/TMEDA/THF (−78 °C) furnishes obviously TMEDA‐stabilized o ‐lithiated carbamates, switching to classic trapping reactions with organic electrophiles or Me 3 SiCl [159] . In the case of P ‐asymmetric p ‐methoxyphenyl phosphoroesteramides (RR’=1,3,2‐oxazaphospholidine with ephedrine backbone) [160] and aryl phosphorodiamidates 82 (aryl=phenyl, biphenyl, naphthyl, pyridyl) with 2‐oxo‐ N ‐phenyl‐1,3,2‐diazaphospholidine group, obtained by transamination of (NMe 2 ) 3 with 2‐(phenylaminomethyl)proline, replacement of the remaining NMe 2 group by reaction with aryl‐OH and oxidation with t BOOH, the directed o ‐lithiation/rearrangement with LDA proceeds stereoselectively with total retention of the configuration (Scheme 20b) [161a–d,162a,b] . If the 2‐oxybiphenyl group in 82 (R=Ph) contains a substituent in 3‐position, blocking the 1,3‐rearrangement, an alternative 1,5‐O,C migration to an o ’‐position of the second phenyl ring, known for lithiation of 3‐substituted biphenyl‐2‐yl diethylcarbamide, [163] was not observed [161d] .…”