A Reactivity-Driven Approach to the Discovery and Development of Gold-Catalyzed Organic Reactions

Abstract

Approaches to research in organic chemistry are as numerous as the reactions they describe. In this account, we describe our reactivity-based approach. Using our work in the area of gold-catalysis as a background, we discuss how a focus on reaction mechanism and reactivity paradigms can lead to the rapid discovery of new synthetic tools.

1,2-Boryl Migration Empowers Regiodivergent Synthesis of Borylated Furans

“…Migratory cycloisomerization is a powerful approach effectively used in synthesis of densely functionalized heterocycles. 1 Our group and others have developed a set of transition metal-catalyzed heterocyclization reactions proceeding with migration of various functional groups. 2 Recently, Davies’ group efficiently employed alkynyl aziridine 1 in a gold-catalyzed cycloisomerization toward either 2,4- or 2,5-substituted pyrroles 2 and 3 (Scheme 1 , eq 1).…”

“…We expected formation of a skipped propargyl aldehyde 9 (analogue of 8 ), which was thought to be a key precursor for the synthesis of very useful, yet otherwise challenging to access borylated furans such as 5 , 6 , 7 via a subsequent cycloisomerization reaction (Scheme 2 , eq 4). 1 , 8 However, the reaction of 4 in the presence of BF 3 ·OEt 2 5a did not provide 9 ; allenyl aldehyde 10 was efficiently formed instead (Scheme 2 , eq 4). 9 All attempts to cyclize allene 10 into furan 5 under forcing reaction conditions failed.…”

“…9 All attempts to cyclize allene 10 into furan 5 under forcing reaction conditions failed. Since allenyl aldehydes and ketones are capable substrates for the Cu-catalyzed cycloisomerization reaction toward furans, 1 , 10 we tested transformation of allenyl boronate 10 into furan 5 in the presence of copper catalysts (Scheme 2 , eq 4). Indeed, employment of [CuOTf] 2 ·PhH catalyst led to the formation of borylated furan 5 in a reasonable yield.…”

Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

“…More efficient, convenient and highly stereoselective synthetic routes are still being sought after. In the past decades, gold catalysis has emerged as an important tool in a plethora of fields of synthetic organic chemistry, and after methodological investigations [11–16], the good functional group compatibility of gold catalysts renders gold catalysis a straightforward protocol in the realm of the synthesis of natural products [17–18]. …”

When gold can do what iodine cannot do: A critical comparison

“…In particular, the utilization of gold pre-catalysts has led to numerous elegant contributions in both heterocycle and carbocycle syntheses [14–20]. In general, these processes are easy to perform under simple reaction conditions: Significant redox chemistry is not involved.…”