COPPER-CATALYZED ALLYL ADDITION METHODS FOR THE ENANTIOSELECTIVE SYNTHESIS OF QUATERNARY STEREOCENTERS

I. Enantio- and Diastereoselective Synthesis of Quaternary Stereocenters by CuCatalyzed Addition of Allyl Diboron Reagents to Aldehydes In this chapter, the development of an enantio- and diastereoselective method for copper-catalyzed allyl addition to aldehydes is disclosed for the synthesis of all-carbon quaternary stereocenters α to secondary alcohols. The method is general for a broad scope of aldehydes, including aryl, alkenyl, alkynyl, and alkyl aldehydes. A chiral allyl-copper nucleophile is generated in situ from readily available 1,1-disubstituted allyl diboron reagents. The synthetic utility of the method is demonstrated by a variety of product transformations. Interesting mechanistic insight is gained through experimentation and the construction of a Hammett plot that elucidates a correlation between the electronic nature of aryl aldehydes and the diastereoselectivity obtained. II. Enantioselective, Cu-Catalyzed Synthesis of α-Quaternary Ketones, α-Ketoesters,and Aldehydes by Addition of Allyl Diboron Reagents to Acyl Electrophiles This chapter discusses the expansion of our method for the synthesis of α-quaternary ketones by copper-catalyzed allyl addition to acyl carbonates. The addition into other readily available acyl electrophiles (dimethyl oxalate and methyl formate) to synthesize α-ketoesters and aldehydes with quaternary carbons is also described. The method proceeds by in situ formation of a chiral allyl-copper nucleophile from readily available 1,1-disubstituted allyl diboron reagents. Acyl carbonates, readily obtained from the corresponding carboxylic acid, react to afford ketones in excellent yields and enantioselectivities. Product derivatizations demonstrate the synthetic utility of the protocol and mechanistic experiments provide insight into the effects of a protic additive. III. Efforts Towards the Enantioselective Synthesis of Heteroatom-SubstitutedQuaternary Stereocenters Chapter three contains the efforts made towards an enantioselective method for the synthesis of α-tertiary alcohols and amines by allyl diboron additions into electrophilic sources of oxygen and nitrogen. Specifically, nitrosobenzene and azodicarboxylates (e.g. DIAD) have been used for this goal. The optimization of these processes is currently ongoing and the work thus far is discussed.