Enantioselective Copper‐Catalyzed Formal [2+1] and [4+1] Annulations of Diynes with Ketones via Carbonyl Ylides

Abstract

Carbonyl ylides have proven to be powerful synthons for the efficient construction of various valuable O‐heterocycles, and the formation of carbonyl ylides by the reaction of metal carbenes with carbonyls has attracted increasing attention over the past decades. However, a catalyst‐controlled highly enantioselective reaction of carbonyl ylides from metal carbenes is extremely challenging. Herein, we report a novel copper‐catalyzed asymmetric formal [2+1] and [4+1] annulations of diynes with ketones via carbonyl ylides. Importantly, this protocol not only represents the first example of successful asymmetric epoxidation via carbonyl ylides, but also constitutes the first reaction of vinyl cations with carbonyl compounds. This method leads to the divergent, practical and atom‐economical synthesis of a range of chiral oxiranes and dihydrofurans in moderate to excellent yields with generally excellent enantioselectivities and diastereoselectivities via remote‐stereocontrol strategy.

Copper-catalyzed formal [4 + 1] annulation ofN-propargyl ynamides with diketones

“…On the basis of the above experimental results and our previous study on the copper-catalyzed cyclization of N -propargyl ynamides, 6 a plausible reaction mechanism to rationalize the formation of pyrrole-substituted dioxole 3a is shown in Scheme 3. First, the Cu( i ) catalyst preferentially coordinates with the electron-richer amide-tethered CC bond of 1a to lead to the precursor A .…”

“…In the past decade, the chemistry of vinyl cations has received particular attention because of their unique carbene-like reactivity. 4 During our recent studies on the copper-catalyzed diyne cyclization, 5,6 we very recently disclosed a copper-catalyzed asymmetric formal [2 + 1] and [4 + 1] annulations of N -propargyl ynamides with ketones via carbonyl ylides, leading to the divergent, practical and atom-economical synthesis of a range of chiral oxiranes and dihydrofurans in moderate to excellent yields with generally excellent enantioselectivities. 6 g Importantly, this protocol represents the first reaction of vinyl cations with carbonyl compounds.…”

“…On the other hand, the use of chiral copper catalyst leads to the chiral product through asymmetric annulation by a remote control of enantioselectivity. 6…”

Brønsted acid–catalyzed asymmetric dearomatization for synthesis of chiral fused polycyclic enone and indoline scaffolds

“…2B, middle). Very recently, our group disclosed the CADA reactions of naphthol-, phenol-, and pyrrole-ynamides (43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53) via direct activation of the electron-rich alkynes by BAs, leading to various valuable spirocyclic enones and 2H-pyrroles bearing a chiral quaternary carbon stereocenter with excellent chemo-, regio-, and enantioselectivities (Fig. 2B, middle) (54).…”

Copper-catalyzed intermolecular formal (5 + 1) annulation of 1,5-diynes with 1,2,5-oxadiazoles

“…In the past decade, the chemistry of vinyl cations has received particular attention because of their unique carbene-like reactivity 36,37 . Recently, our group reported a copper-catalyzed diyne cyclization via vinyl cations as key intermediates, providing a variety of polycyclic pyrrole derivatives [38][39][40][41][42][43][44][45][46][47] . In particular, the related catalytic asymmetric transformations were established via a remote control of enantioselectivity.…”