Catalytic enantioselective preparation of alpha-substituted allylboronates and their use in synthesis.

摘要

Over the past few decades, despite remarkable advances in boron chemistry, chiral alpha-substituted allylboronates have been neglected. This can be attributed to their difficult synthesis and their moderate stability. Nevertheless, they have shown great potential for stereocontrolled additions to aldehydes. Chapter 2 presents a study of the behavior of alpha-substituted allylboronates in Lewis acid-catalyzed additions to aldehydes. This study provided key information on the nature of the transition state in such reactions and solved the problem of E/Z selectivity, an important limitation in the use of chiral alpha-substituted allylboronates in stereocontrolled additions.;Chapter 6 describes preliminary results in the development of even more challenging applications for chiral alpha-substituted allylboronate reagents. Ketone allylation is achievable but only when the reagent is transformed to the corresponding chiral alpha-substituted allyltrifluoroborate salt. This approach is limited as only modest control on the E/Z selectivity of the process was achieved. Nevertheless, this represents a novel method for stereocontrolled additions to ketones with potassium trifluoroborate reagents. Also, imine allylation with chiral alpha-substituted allylboronate reagents was achieved when using primary and secondary imines. With primary imines, the reaction proceeded with high stereoselectivity, modest E/Z selectivity and modest yield. With secondary imines, the reaction required an excess amount of Lewis acid in order to proceed. This approach provided secondary homoallylic amines in good yield, good E/Z selectivity but with poor stereoselectivity.;The use of a catalytic, enantioselective allylic substitution reaction provided a new approach to chiral alpha-substituted allylboronates. As shown in Chapter 3, chiral alpha-alkyl allylboronates can easily be prepared with high enantioselectivity. To provide a practical use of alpha-alkyl allylboronate reagents, a one-pot asymmetric allylic substitution/aldehyde allylation reaction was developed (Chapter 4). The one-pot reaction sequence affords enantioenriched homoallylic alcohols with high selectivity and yield. As exemplified in Chapter 5 through the total synthesis of two small delta-lactone natural products, this one-pot sequence is easily scalable and the products can be efficiently transformed to more complex scaffolds.