Ligand‐Controlled Palladium‐Catalyzed Carbonylation of Alkynols: Highly Selective Synthesis of α‐Methylene‐β‐Lactones

Abstract

The first general and regioselective Pd-catalyzed cyclocarbonylation to give a-methylene-b-lactones is reported. Keyt ot he success for this process is the use of as pecific sterically demanding phosphine ligand based on N-arylated imidazole (L11)i nt he presence of Pd(MeCN) 2 Cl 2 as precatalyst. Av ariety of easily available alkynols provideu nder additive-free conditions the corresponding a-methylene-blactones in moderate to good yields with excellent regio-and diastereoselectivity.T he applicability of this novel methodology is showcased by the direct carbonylation of biologically active molecules including natural products. Scheme 1. Natural compounds and biologically active molecules with a-methylene-b-lactone skeleton.

Tropane-Based Dispirocyclic Oxiranes and Spirocyclic Ketones

“…1 H NMR (400 MHz, CD 3 OD):  = 4.06-4.01 (m, 2 H), 2.36 (t, J = 7.7 Hz, 2 H), 2.25 (t, J = 7.2 Hz, 2 H), 2.12 (dd, J = 15.3, 2.1 Hz, 2 H), 1.94 (ddd, J = 28. 5,15.1,5.8 Hz,6 H), 1.81 (t, J = 6.8 Hz, 2 H). 13 C NMR (101 MHz, CD 3 OD):  = 220.…”

“…3 The conformationally restrained tropane scaffold is among the most frequently found heterocyclic scaffolds in FDA-approved drugs and drug candidates. 4 Spirocyclic systems in which the tropane fragment is connected to four-, 5 five-, 6 and six-membered 7 oxygen-containing heterocycles possess various biological activities and demonstrate a synergism of tropane and spirocyclic 8 structural motifs. Spirotropane oxiranes have been used as starting materials for the synthesis of numerous biologically active compounds.…”

Ligand‐Controlled Palladium‐Catalyzed Carbonylation of Alkynols: Highly Selective Synthesis of α‐Methylene‐β‐Lactones

“…Notably,t he molecular structure of ethynyl estradiol derivative 2x was unambiguously confirmed by X-ray structure analysis. [10] Similarly, a-methylene-blactones 2ab-2af derived from other steroid hormones such as dihydrocholesterol, stanolone and epiandrosterone,w ere obtained in 41-87 %y ields with excellent selectivity.M oreover, homopropargylic alcohols also proved to be suitable substrates and afforded the corresponding 5-membered products with excellent regioselectivity (see Supporting Information, Scheme S2).…”

Palladium‐Catalyzed Cascade Carbonylation to α,β‐Unsaturated Piperidones via Selective Cleavage of Carbon–Carbon Triple Bonds

“…[11] Recently,w es tarted to investigate the alkoxy-and aminocarbonylation of propargylic alcohols. [12] During the course of this work, we discovered that a,b-unsaturated piperidones can be synthesized in as traightforward and general manner by an ew palladium-catalyzed cascade carbonylation of alkynols and aliphatic amines through highly selective CC cleavage reaction (Scheme 1c).…”