Enantioselective Lewis acid-catalyzed allylboration of aldehydes using camphor-derived diols: Development and synthetic applications

Aldehyde allylboration chemistry has been an essential tool in organic synthesis for many decades. Even though many methods are available, none of them possesses all of the desired attributes. One would hope to develop a method that would be general, provide consistently high yield and selectivity, be compatible with a wide range of substrates, easy to perform, environmentally friendly, and catalytic. In the course of our studies on the Lewis acid-catalyzed allylboration of aldehydes, we found that the use of a camphor-derived chiral auxiliary in conjunction with Sc(OTf)3 provided us with allylic boronate reagents that are stable to purification by silica gel and could be manipulated without particular precaution. These reagents afforded the desired homoallylic alcohols in good yield and excellent enantioselectivity. Chapter 2 describes our work in the development and optimization of this new catalytic method for the allylboration reaction.; The successful application of the camphor-derived diols in this reaction justified our investigation into the development of new preparations of this chiral auxiliary. The two new syntheses of the desired diol are described in Chapter 3. The first approach was executed in two steps from camphorquinone in 55% overall yield and purified by a single final recrystallization. The second route made use of simple camphor as starting material, and provided the final diol in four steps in 55% overall yield and required only a recrystallization for purification after the final step.; The generality of the catalytic conditions was tested in its application to the additions of alpha-silyl substituted allylic boronates described in Chapter 4. Unfortunately, under the catalytic manifold, this class of boronates provided either the allylsilation product or an unseparable mixture of products.; Finally, Chapter 5 presents our work towards the synthesis of psymberin using our Lewis acid-catalyzed allylboration of aldehydes. The application of the Lewis acid-catalyzed allylboration allowed us to prepare the desired homoallylic alcohol resulting from the reaction between a methallylboronate and D-(R)-glyceraldehyde acetonide in 75% yield as a single diastereoisomer. An advanced intermediate containing the pyran core was also obtained through the tandem IEDHDA/allylboration reaction in 50% yield and good enantioselectivity (86%).