In the course of our studies on the vinylation of nitrones, we had found that vinylboronic esters, in the presence of dialkylzincs, could transfer their vinylic chain onto nitrones. We had developed this method with pinacol esters, since these reagents offer two important advantages: they are very easily accessible by hydroboration of 1-alkynes, and they are air- and water- stable, thus can be purified and stored.
But we also found that these pinacolboronic esters were poorly reactive. We couldn't use mild reaction conditions that would have been compatible with sufficient chemoselectivities. Thus, we sought for other vinylboronic esters that would be as stable, as easy to handle, and as accessible as pinacolboronic esters, but that would nevertheless be more reactive. This brought us to study the preparation and use of 4,4,6-trimethyl-1,3,2-dioxaborinane (or MPBH for MethylPentanediolBorane) in hydroboration. This reagent had been disclosed in 1966 and its stability had been noticed, but has seldom been used ever since.
We describe in the first chapter of this thesis our development of convenient, cost-effective, scalable, fast preparations of MPBH, and in chapter 2 its use in the hydroboration of 1-alkynes catalyzed by Cp2ZrHCl. This hydroboration is high yielding and chemoselective, allowing the preparation of E vinylboronic esters with functionalized side chains under very simple and robust conditions.
In chapter 3 are detailed our studies on the preparation of N-hydroxy-allyl-amines by reaction of a vinylboronic ester derived from MPBH, a nitrone and dimethylzinc. Compared to our former work on this reaction, new and milder conditions have been found that give access to functionalized N-hydroxy-allyl-amines in good yields. We compare the relative reactivity of MPBH and pinacolborane (PinBH) in Zr-catalyzed hydroboration. We compare also the relative reactivities of diversely hindered vinylboronic ester in the reaction with nitrones, and we propose a discussion on the mechanism of the latter reaction.
With MPBH now easily available, it was tempting to use it for the borylation of aryl halides, since this is a very efficient, broad-scope, atom-economic access to the very useful class of arylboronic derivatives. Chapter 4 describes successful borylation of aryl iodides, bromides, triflates and chlorides with MPBH and two different Palladium-based catalytic systems. High yields and selectivities are attained.
In the last chapter, we confirm that the arylboronic esters can be readily used for the Suzuki-Miyaura coupling, which is the principal application of this reagents family. |
