Mild and Efficient Synthesis of Benzo-Fused Seven- and Eight-membered Ring Lactams: A Convenient Approach to Biologically Interesting Chemotypes

Synthesis of Benzo[b]azocin‐2‐ones by Aryl Amination and Ring‐Expansion of α‐(Iodophenyl)‐β‐oxoesters

“…TLC was performed on aluminum plates coated with SiO 2 F 254 . 1 H, 19 Fa nd 13 CNMR spectra were recorded on Bruker AvanceD RX 500 and 300 instruments. Multiplicities of carbon signals were determined with DEPT experiments.…”

“…[11,12] An obvious synthetica ccess to hexahydrobenzo[b]azocin-2-one derivatives is provided by Beckmann rearrangement of oximesf rom benzosuberones. [13] Al ess evident, though very efficient access to the target structure is achievedb yo xidative cleavage of cyclopenta[b]indole derivatives with periodate. [14] Not necessarily most effective, but very interesting routes to eight-membered ring lactamsi nvolve ring expanding transformations.…”

Yttrium‐Catalyzed Intramolecular Hydroalkoxylation/Claisen Rearrangement Sequence: Efficient Synthesis of Medium‐Sized Lactams

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An efficient yttrium-catalyzed intramolecular hydroalkoxylation/Claisen rearrangement sequence has been achieved, thus enabling facile access to ad iverse array of valuable medium-sized lactams.F urthermore,amechanistic rationale for this novel cascade reaction is well supported by av ariety of control experiments.Medium-sized lactams (8-to 11-membered rings), especially the eight-membered lactams (benzazocinones), are important structural motifs which have been found in bioactive molecules and natural products (Figure 1). [1] However,s uch units are regarded as difficult structures to access because of entropic effects and transannular interactions, [2] and only very limited methods have been developed to date, [3][4][5] with intramolecular carbonylation [3] and ring-closing metathesis (RCM) [1e,4] being the most popular choices.T hus, new methods for the efficient construction of this type of skeleton are highly desired.Supportinginformation for this article can be found under: http://dx.

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“…Medium-sized lactams (8-to 11-membered rings), especially the eight-membered lactams (benzazocinones), are important structural motifs which have been found in bioactive molecules and natural products (Figure 1). [1] However,s uch units are regarded as difficult structures to access because of entropic effects and transannular interactions, [2] and only very limited methods have been developed to date, [3][4][5] with intramolecular carbonylation [3] and ring-closing metathesis (RCM) [1e,4] being the most popular choices.T hus, new methods for the efficient construction of this type of skeleton are highly desired.…”

“…[8a] In 2015, Toste et al disclosed its enantioselective version by asymmetric desymmetrization strategy (Scheme 1c). [8b] Despite these remarkable achievements,these intramolecular cascade reactions have so far been limited to noble-metal catalysts.In addition, the construction of important medium-sized rings by this strategy has not been reported to date.I nspired by our recent study on ynamide chemistry, [10,11] we envisioned that the synthesis of eight-membered benzolactams (2)m ight be achieved by catalytic intramolecular hydroalkoxylation of ynamides (1)and subsequent Claisen rearrangement. Herein, we describe the realization of such an yttrium-catalyzed tandem intramolecular hydroalkoxylation/Claisen rearrangement, thus allowing the atom-economical synthesis of various synthetically useful benzazocinones (Scheme 1d).…”