Chiral Camphor-Based 1,3- and 1,4-Amino Alcohols and Aminodiols as Ligands for Diethylzinc Addition to Aldehydes

Olusegun B Olubanwo,James A Golen,Vesa Nevalainen,Arnold L Rheingold

doi:10.4236/ijoc.2018.82018

Abstract

Syntheses of (1R,2S,3R,4S)-1,7,7-trimethyl-2-pyridin-2-ylmethylbicyclo[2.2.1]-heptane-2,3-diol (7), (1R,2S,3R,4S)-1,7,7-trimethyl-2-[(6-methyl)-pyridin-2-ylmethyl-bicyclo-[2.2.1]heptane-2,3-diol (13), and (1R,2S,2’R,4R)-1,7,7-trimethyl-2-piperidin-2-ylmethyl-bicyclo[2.2.1]heptan-2-ol (19b) from commercially available (d)-camphor (1) are described. Key steps of the syntheses involved substrate-controlled diastereoselective alkylation and platinum oxide-catalyzed hydrogenation reactions. These compounds, and other intermediate amino alcohols in their syntheses, were successfully utilized as ligands in enantioselective diethyl zinc (Et2Zn) addition to benzaldehyde with moderate enantioselectivity.

Highlights

Chiral amino alcohols are common precursors to many functional molecules [1]
We have described syntheses and structural characterization of six new camphor-based amino alcohols and diols
These compounds were utilized as ligands for enantioselective additions of Et2Zn to benzaldehydes to obtain 1-phenylethanols

Summary

Introduction

The chelate is capable of catalyzing enantioselective additions of organozincs to aldehydes [2]. The first ligand, (S)-leucinol, used to catalyze the addition of diethylzinc (Et2Zn) to benzaldehyde gave moderate enantioselectivity (49%) as reported by Oguni and Omi in 1984 [3]. In continuation of our ongoing research on the design and synthesis of new chiral ligands for asymmetric reactions [25], we are reporting syntheses of new amino alcohols and amino diols derived from (+)-camphor. The utility of the new ligands for the addition of Et2Zn to benzaldehyde was studied briefly

Result and Discussion

H OH N 28

Findings

Experimental

Conclusions