Philip N. Moquist

Enantioselective Addition of Boronates to Chromene Acetals Catalyzed by a Chiral Brønsted Acid/Lewis Acid System

Chiral α,β-dihydroxy carboxylic acids catalyze the enantioselective addition of alkenyl- and aryl boronates to chromene acetals. The optimal carboxylic acid is a tartaric acid amide, easily synthesized via a 3-step procedure. The reaction is enhanced by the addition of Lanthanide triflate salts such as cerium(IV)-and ytterbium(III) triflate. The chiral Bronsted acid and metal Lewis acid may be used in as low as 5 mol % relative to acetal substrate. Optimization of the reaction conditions can lead to yields >70% and enantiomeric ratios as high as 99:1. Spectroscopic and kinetic mechanistic studies demonstrate an exchange process leading to a reactive dioxoborolane intermediate leading to enantioselective addition to the pyrylium generated from the chromene acetal.

The Mechanism and an Improved Asymmetric Allylboration of Ketones Catalyzed by Chiral Biphenols

A mechanistic study of the enantioselective asymmetric allylboration of ketones with allyldiisopropoxyborane catalyzed by chiral biphenols resulted in the development of improved reaction process. In a ligand exchange process involving the chiral biphenol and the boronate to liberate isopropanol as the key step, addition of isopropanol to the reaction was found to increase the overall rate and enantioselectivity. In the design of an improved reaction, a boronate possessing a tethered alcohol would more readily liberate catalyst at the end of a reaction. The use of allyldioxaborinane with 2 mol% (S)-3,3′-Br2-BINOL and 2 equivalents t-BuOH relative to ketone at room temperature results in high yields and enantioselectivities. Insight gathered from the mechanistic investigation resulted in the development of a reaction process that uses less catalyst (from 15 mol% to 2 mol%) at warmer temperatures (from -35 °C to room temperature).

Catalytic Diastereoselective Petasis Reactions

Multicomponent Petasis reactions: the first diastereoselective Petasis reaction catalyzed by chiral biphenols that enables the synthesis of syn and anti β-amino alcohols in pure form has been developed. The reaction exploits a multicomponent approach that involves boronates, α-hydroxy aldehydes, and amines.

Enantioselective boronate additions to N-acyl quinoliniums catalyzed by tartaric acid.

Tartaric acid catalyzes the asymmetric addition of vinylboronates to N-acyl quinoliniums, affording highly enantioenriched dihydroquinolines. The catalyst serves to activate the boronate through a ligand-exchange reaction and generates the N-acyl quinolinium in situ from the stable quinoline-derived N,O-acetal.

Enantioselective Synthesis of 1,2-Dihydronaphthalene-1-carbaldehydes by Addition of Boronates to Isochromene Acetals Catalyzed by Tartaric Acid

Tartaric acid is an ideal asymmetric catalyst as it is abundant, cheap, and environmentally friendly. (+)-Tartaric acid was found to catalyze a novel enantioselective [4 + 2] cycloaddition of isochromene acetals and vinylboronates. A variety of substituted isochromene acetals were tolerated, furnishing the desired dihydronaphthalenes and dihydrobenzofluorene products in good yields. High enantiomeric ratios (up to 98.5:1.5) and excellent diastereoselectivities (all >99:1) were observed employing 10 mol % of (+)-tartaric acid as the catalyst, in combination with 5 mol % of Ho(OTf)3.