Desymmetrization of Diols by Phosphorylation with a Titanium-BINOLate Catalyst

Abstract

The desymmetrization of ten prochiral diols by phosphoryl transfer with a titanium-BINOLate complex is discussed. The phosphorylation of nine 1,3-propane diols is achieved in yields of 50–98%. Enantiomeric ratios as high as 92:8 are achieved with diols containing a quaternary C-2 center incorporating a protected amine. The chiral ligand, base, solvent, and stoichiometry are evaluated along with a nonlinear effect study to support an active catalyst species that is oligomeric in chiral ligand. The use of pyrophosphates as the phosphorylating agent in the desymmetrization facilitates a user-friendly method for enantioselective phosphorylation with desirable protecting groups (benzyl, o-nitrobenzyl) on the phosphate product.

Mechanistic Applications of Nonlinear Effects in First‐Row Transition‐Metal Catalytic Systems

“…reported the asymmetric phosphorylation of diols catalyzed by titanium (Scheme 7). [ 16 ] According to the results of previous studies on active titanium BINOLate complexes, compounds INT‐3 and INT‐4 , which are in equilibrium with one another were supposed to be the possible active catalysts. [ 17 ] However, under conditions that are conducive to shifting the equilibrium towards compound INT‐4 (cooling, reducing the ratio of ligand to metal), a significant decrease in the enantioselectivity of the product was found.…”

Recent developments in enantioselective titanium-catalyzed transformations

“…Moreover, the indoline arene moiety could exhibit electron-withdrawing and electrondonating substituents at either C4, C5 or C6 position of the substrate. The same year, Sculimbrene et al investigated the desymmetrization of 2,2-disubstituted-1,3-diols 206 through phosphorylation in the presence of a titanium catalyst derived from (R)-BINOL [152]. As illustrated in Scheme 72, the reaction employed tetrabenzyl pyrophosphate (TBPP) as the phosphorylating agent and was performed at 0 °C in dichloromethane as the solvent.…”

Recent Advances in Nonprecious Metal Catalysis

“…Sculimbrene and coworkers reported the Ti-catalyzed desymmetrization of 1,3-propanediols via phosphorylation (Scheme 53). 131 The reaction is conducted under mild conditions with the relatively stable phosphorylating agent TBPP and affords the monophosphorylated products in excellent yields with up to 92:8 er from protected 2-amino-1,3-propanediols. A relatively high catalyst loading (10 mol % Ti and 20 mol % BINOL) is required, although the ligand is inexpensive.…”