A GaCl₃-Catalyzed [4+1] Cycloaddition of α,β-Unsaturated Carbonyl Compounds and Isocyanides Leading to Unsaturated γ-Lactone Derivatives

Abstract

A GaCl3-catalyzed reaction of alpha,beta-unsaturated ketones with isocyanides leading to the formation of unsaturated lactone derivatives is described. This is the first example of the catalytic [4+1] cycloaddition of alpha,beta-unsaturated ketones and isocyanides. GaCl3 is an excellent catalyst due to its lower oxophilicity, which is desirable for all of the key steps, such as E/Z isomerization, cyclization, and deattachment from the products.

A computational study on the mechanism for the GaCl3-catalyzed [4+1] cycloaddition of α,β-unsaturated ketone and 2,6-dimethylphenyl isocyanide

“…Therefore, a catalytic amount of GaCl 3 can promote the title reaction to give the product in high yield, just as observed by Chatani et al 12 3.4. The reaction process without GaCl 3 activator…”

“…Chatani et al 12 used toluene as the solvent for the title reaction in their experimental study. Accordingly, in order to take into account the solvent effect, we performed the single-point energy calculations using the SCRF/PCM method at the B3LYP/6-31G* level.…”

“…Recently, GaCl 3 was used as a good activator in many organic reactions. [5][6][7][8][9][10][11] Chatani and co-workers 12 reported that GaCl 3 can promote the cycloaddition of a,b-unsaturated carbonyl compounds with isocyanides leading to unsaturated g-lactone derivatives.…”

Oligosubstituted Pyrroles Directly from Substituted Methyl Isocyanides and Acetylenes

“…Due to their formally divalent terminal carbon atom, isocyanides are unique organic nitrogen derivatives. Consequently, they have found wide use in organic synthesis, [7] especially in multicomponent reactions, [8] different types of insertions [9,10] and cycloadditions, [11] giving rise to a large variety of nitrogen-containing compounds. Cycloadditions are possible due to the ability of substituted methyl isocyanides to be metallated in the a-position, as first observed by Schçllkopf and Gerhart.…”

Transition-Metal-Catalyzed Reactions in Heterocyclic Synthesis

“…The following cyclization of 490 and the subsequent 1,2-alkyl shift of 491 led to 484. Chatani et al reported the catalytic [4 + 1]-cycloaddition of R, isocyanides 493, leading to unsaturated γ-lactone derivatives 494 (Scheme 149) 211. In the presence of a catalytic amount of GaCl 3 , the reaction of R, -unsaturated ketones 492a and 492b with 2,6-dimethylphenyl isocyanide 493 proceeded in toluene, and the corresponding unsaturated iminolactones 494a and 494b were obtained in high yields.…”