Catalytic asymmetric addition of diorganozinc reagents to N -phosphinoylalkylimines

Abstract

The synthesis of ␣-chiral amines bearing two alkyl groups has been hampered by the accessibility and stability of the alkylimine precursor. Herein, we report an efficient strategy to generate the alkyl-substituted imine in situ that is compatible with the MeDuPHOS monoxide⅐Cu(I) catalyzed addition of diorganozinc reagents. The sulfinic acid adduct of the imine is readily prepared by mixing diphenylphosphinic amide, the aldehyde, and sulfinic acid. The sulfinic acid adduct is generally isolated by filtration. The addition of diorganozinc reagents in the presence of Me-DuPHOS monoxide⅐Cu(I) and the in situ-generated imines affords the corresponding ␣-chiral amines in high yields and enantiomeric excesses.

Asymmetric Mannich Reactions with in Situ Generation of Carbamate-Protected Imines by an Organic Catalyst

“…Palomo 5a and the group of Herrera, Bernardi, and Ricci 5b independently reported highly enantioselective aza-Henry reactions with in situ generation of carbamate-protected aryl and alkyl imines from α-amido sulfones 1A 6 promoted by a chiral phase-transfer catalyst, thereby establishing asymmetric Mannich reactions tranforming directly the stable α-amido sulfones 1 into the corresponding aza-Henry (Mannich) adducts. Although chiral organic catalysts not based on PTC (phase transfer catalysis) have emerged as versatile catalysts for asymmetric Mannich reactions, to our knowledge, the development of practical asymmetric Mannich reactions with in situ generation of carbamate-protected imines catalyzed by such chiral organic catalysts has not yet been reported …”

N-Phosphinoylimines: An Emerging Class of Reactive Intermediates for Stereoselective Organic Synthesis

“…An approach was recently described by Charette and coworkers for the in situ preparation of these imines via elimination of the corresponding sulfone 15. 13 These compounds were efficiently prepared by the reaction of the corresponding aldehydes and P,P-diphenylphosphinic amide in the presence of p-toluenesulfinic acid (Scheme 7). Treatment of sulfone 15 with a strong base, such as an organometallic reagent, afforded the N-phosphinoylimine which was subsequently utilized in asymmetric additions (vide infra).…”

“…More recent results from the Charette lab involve the use of alkyl-substituted N-phosphinoylimines 110. 13 Imines 110 are formed via the in situ elimination of the corresponding a-tosyl phosphinamide 109 (cf. Scheme 7).…”

Highly Stereoselective Synthesis of Substituted γ‐Lactams from Acylsilanes

“…We chose the diphenylphosphoryl group because of a) its electron-withdrawing capacity, b) the steric magnitude associated with this functionality, which might provide nonbonding interactions during the addition event and influence diastereoselection, and c) the ease of removal of this group under acidic conditions, which could facilitate cyclization to the g-lactam. [34][35][36][37][38][39][40][41] Gratifyingly, this three-component reaction provided the g-amino-b-hydroxy amide in 74 % yield and greater than 20:1 diastereomeric ratio after desilylation ( Table 1, entry 1). An examination of the imine scope of the reaction demonstrates that the reaction proceeds in good yields in the presence of both electron-deficient (Table 1, entries 2 and 3) and electron-rich (Table 1, entries 4 and 5) aromatic systems.…”