Build/Couple/Pair Strategy Combining the Petasis 3-Component Reaction with Ru-Catalyzed Ring-Closing Metathesis and Isomerization

Abstract

A "build/couple/pair" pathway for the systematic synthesis of structurally diverse small molecules is presented. The Petasis 3-component reaction was used to synthesize anti-amino alcohols displaying pairwise reactive combinations of alkene moieties. Upon treatment with a ruthenium alkylidene-catalyst, these dienes selectively underwent ring-closing metathesis reactions to form 5- and 7-membered heterocycles and cyclic aminals via a tandem isomerization/N-alkyliminium cyclization sequence.

Preferential Oxidation of CO in H2 on Pure Co3O4−x and Pt/Co3O4−x

“…Based on the initial results and our previous experience with Petasis reactions,5b,12 optimization was focused on solvent selection for the reaction between dihydroxylactam 2a and [( Z )‐1‐propen‐1‐yl]boronic acid (Table 1). First of all, in the absence of BF 3 · OEt 2 (Entries 1 and 2), no conversion of the starting dihydroxylactam 2a was observed, indicating that a Lewis acid is indeed necessary for the formation of the N ‐acyliminium ion.…”

Synthesis of Heterocycles through Transition‐Metal‐Catalyzed Isomerization Reactions

“…Formation of oxazabicyclooctane 42 was speculated to proceed by means of RCM, isomerization, and intramolecular attack from the hydroxyl group. In a later report,24 extensive optimization studies were carried out to identify reaction conditions providing access to both tetrahydroazepines 41 and oxazabicyclooctanes 42 . Thus, the use of the Grubbs II catalyst at room temperature was found to provide minimal pre‐metathetic isomerization, whereas the use of the Hoveyda–Grubbs II catalyst in refluxing toluene provided maximal post‐metathetic isomerization.…”

“… Synthesis of oxazabicyclooctanes via tandem RCM/isomerization/ O ‐cyclization of N ‐alkyliminium ions 20. 24 …”

2-Methyltetrahydrofuran as a Solvent of Choice for Spontaneous Metathesis/Isomerization Sequence

“…34,35 The metathesis/isomerization sequence was exploited, for example, in the synthesis of centrolobine derivatives. 36,37 Reactions leading to cyclic vinyl ethers, 38,39 amines, 39,40 and lactams, 39,41,42 whereby double bond migration was induced by simple heating of the reaction mixture without any chemical triggers, are also possible. However, in most cases, utilization of specially prepared substrates was crucial to achieve satisfactory yields.…”