A Silver(I)-Catalyzed Intramolecular Ficini's [2 + 2] Cycloaddition Employing Ynamides.

摘要: We reported the first examples of Ficini’s [2 + 2] cycloaddition, or Ficini reaction, employing ynamides in 2010 after a 13-year long attempt.1 This final success came more than 40 years Ficini2–5 had disclosed perhaps most useful carbon-carbon bond forming reaction involving ynamines.2,6 The reaction3 entails stepwise and thermally driven cycloaddition7 ynamines with α,β-unsaturated ketones, while our reaction1 1 were promoted Cu(II)/Ag(I) salts, leading to formation cyclobutenamides 3 via proposed zwitter ionic intermediate 2 [Scheme 1]. Mezzetti8 subsequently beautiful account asymmetric cycloadditions using chiral dicationic Ru(II) complex. However, an intramolecular variant has remained untapped ynamides.9 Given that have become powerful versatile functional group organic synthesis last 20 years,10,11 successful tethered enone motif as shown 4 could prove be tantalizing possibility for constructing complex polycycles. wish communicate here establishing concept cycloaddition its current limitations. Scheme 1 Ficini’s Cycloaddition Using Ynamides. Our work commenced new finding experimentally intermolecular cycloaddition. observed it is not necessary use both Cu(II) Ag(I) catalysts promote reaction. As Table 1, initial keys render are cannot terminally unsubstituted 7 [entries 2], mol% CuCl2 60 AbSbF6 found suitable catalytic system1 afford desired cycloadduct 10 high yield from ynamide 9 [entry 3]. efforts post publication reveal either salt alone catalyze this silver actually superior. More specifically, AgNTf2 appears best catalyst overall 10]12 providing comparable outcome those by AbSbF6. While AgBF4 also worked quite effectively 6], took much longer time 6–8]. Table 1 The Effectiveness Silver Salts. The discovery proves out essential, turned presence completely ineffective 11a–d.13–15 Consequently, we focused on quickly again was 1–3 versus entry 2]. In addition, yields better when carried CH2Cl2 entries 6–9] at higher concentrations 12 11].16 Lastly, nature electron withdrawing nitrogen atom did appear significant impact 13–15]. Table 2 A Ag(I)-Catalyzed Intramolecular Cycloaddition. Relative stereochemistry assigned nOe experiments performed 12a [Figure 1], scope showcased Figure 2. It noteworthy substituted alkene, lower [see 13–16]. likely due competing complexation olefin followed decomposition pathways. Only there sufficient distance between atom, improved 16]. Figure 1 Stereochemical Assignment Experiment. Figure 2 Scope Cycloaddition. Unfortunately, hope obtaining 21, instead only half-cycloaddition product 22 numerous attempts relative unassigned, isolation result direct hydrolysis 23 formation, although taken place, subsequent hydrolytic ring-opening 21 lead 22. On other hand, utilizing AgOTf catalyst, find corresponding 24 11a. all cases, cycloadducts which cyclobutenamide fused 6-membered ring prepared without problem. distinct contrast suggests strain anticipated where 5-membered ring, responsible deterring pathway.17 Scheme 2 Observations Half-Cycloaddition Products. We then examined electrocyclic these cycloadducts.18 Scheme 3, highly torquoselective conrotatory 12d take place 100 °C 2-amidodienes 25a 25d, respectively. Likewise, 26 27 obtained their respective starting 15 16. level torquoselectivity predictably ring-junction hydrogen [in blue] rotating inwardly respect cyclobutene avoid trans-cyclohexene ring. rotational preference trumps inward rotation favored carbonyl based Houk’s prediction,19 leads exclusive Z-vinylogous amide, experiments. Scheme 3 Pericyclic Ring-Opening Cycloadducts. In favor S-trans conformation ∆E being 4.03 kcal mol−1 B3LYP/6-31G* [Spartan™] calculations. Such conformational allylic strain. preliminary carry obvious application form [4 27, latter attempt possible cycloaddition.20 currently exploring applications can distinctly showcase synthetic potential functionalized unique dienes. We described N-sulfonyl motif. catalyzed AgNTf2. Our represents original ynamine–[2 Efforts underway further development applications.