Chiral α-Stereogenic Oxetanols and Azetidinols via Alcohol-Mediated Reductive Coupling of Allylic Acetates: Enantiotopic π-Facial Selection in Symmetric Ketone Addition

Abstract

Iridium-tol-BINAP-catalyzed reductive coupling of allylic acetates with oxetanones and azetidinones mediated by 2-propanol provides chiral α-stereogenic oxetanols and azetidinols. As illustrated in 50 examples, complex, nitrogen-rich substituents that incorporate the top 10 N-heterocycles found in Food and Drug Administration (FDA)-approved drugs are tolerated. In addition to 2-propanol-mediated reductive couplings, oxetanols and azetidinols may serve dually as reductant and ketone proelectrophiles in redox-neutral C–C couplings via hydrogen autotransfer, as demonstrated by the conversion of dihydro-1a and dihydro-1b to adducts 3a and 4a, respectively. The present method delivers hitherto inaccessible chiral oxetanols and azetidinols, which are important bioisosteres.

Access to 4‐Membered Heterocycles via Visible‐Light Triggered Intramolecular Cyclization from Alkynes: Bypassing Unfavorable 4‐endo‐dig Cyclization

“…(18)(19)(20)(21)(22)(23). In addition, it was revealed that our protocol is compatible with a wide range of functional groups, maintaining reaction efficiency irrespective of the electronic properties of the substituents in the aromatic ring (24)(25)(26)(27)(28)(29)(30)(31). Interestingly, a series of oxetane-3-ones derived from heteroaryl propargylic alcohols including thiophene (32), pyridine (33) and benzothiophene (34) could be accessed by the present method.…”

“…Among these strategies, a notable success has been achieved by employing oxetan‐3‐ones and azetidine‐3‐ones as versatile synthons for oxetane and azetidine, respectively (Figure 1A). [2,9,25–37] …”

“…[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] Among these strategies, a notable success has been achieved by employing oxetan-3-ones and azetidine-3ones as versatile synthons for oxetane and azetidine, respectively (Figure 1A). [2,9,[25][26][27][28][29][30][31][32][33][34][35][36][37] While highly enabling, the preparation of these building blocks remains challenging in the context of diversification of the substitution patterns. 3,3-Disubstituted oxetanes and azetidines have typically been envisioned via conventional synthetic methods through Michael acceptors or Bus-ketimines derived from oxetaneone and azetidinones.…”

Asymmetric Synthesis of Trisubstituted Vicinal Diols through Copper(I)‐Catalyzed Diastereoselective and Enantioselective Allylation of Ketones with Siloxypropadienes

“…In 2021, they achieved the first enantioselective carbonyl reductive coupling of 1‐alkoxy‐1‐methyl‐propadiene under ruthenium catalysis, which afforded trisubstituted chiral vicinal diols in moderate yields with high both diastereoselectivity and enantioselectivity [13b] . Later, the same group also succeeded in the Ir‐catalyzed asymmetric reductive coupling of oxetanones and phthalimido‐allene [13c] . Moreover, Breit and co‐workers developed a dual palladium/photoredox‐catalyzed enantioselective decarboxylative hydroaminoalkylation of alkoxyallenes with amino acids in 2021, which worked formally as a reductive allylation of aldimines [14] …”