Pd- and Rh-Catalyzed Hydroarylation of γ-(2-Methoxycarbonylphenyl)propargylic Alcohols: Approaches to 4- or 5-Substituted Seven-Membered Benzolactones and 3,3-Disubstituted Phthalides

Abstract

A study of the palladium-catalyzed hydroarylation/hydrovinylation reaction of γ-(2-methoxycarbonylphenyl)propargylic alcohols with aryl iodides/vinyl triflates and of the rhodium-catalyzed one with organoboron derivatives is described. The opposite regiochemical outcome of the two processes allows an easy selective approach to 5- or 4-substituted benzoxepin-1(3H)-ones by combining the hydroarylative/hydrovinylative step with cyclocondensation between -OH and -COOMe groups in the intermediate γ,γ-disubstituted or β,γ-disubstituted allylic alcohols. A one-flask procedure to give benzo[c]oxepin-1(3H)-ones directly from the starting alkyne has been also developed. Treatment of crude γ,γ-disubstituted allylic alcohols with NaOH, followed by acidification, affords 3,3-disubstituted phthalides.

Exciting progress in the transition metal‐catalyzed synthesis of oxepines, benzoxepines, dibenzoxepines, and other derivatives

“…Arcadi et al in 2015 used γ‐(2‐methoxycarbonylphenyl)propargylic alcohols 64 as starting compounds in the palladium‐catalyzed hydroarylation/hydrovinylation reaction with aryl iodides/vinyl triflates 65 and then the cyclocondensation to afford 5‐substituted benzo[ c ]oxepin‐1(3 H )‐ones 69 and also the rhodium‐catalyzed reaction with organoborons that led to 4‐substituted benzo[ c ]oxepin‐1(3 H )‐ones 70 (Scheme 19). [ 66 ]…”

“…Arcadi et al in 2015 used γ-(2-methoxycarbonylphenyl) propargylic alcohols 64 as starting compounds in the palladium-catalyzed hydroarylation/hydrovinylation reaction with aryl iodides/vinyl triflates 65 and then the cyclocondensation to afford 5-substituted benzo[c]oxepin-1 (3H)-ones 69 and also the rhodium-catalyzed reaction with organoborons that led to 4-substituted benzo[c]oxepin-1 (3H)-ones 70 (Scheme 19). [66] Roux et al in 2011 succeeded to synthesize 3-amino-2,2-dihydro-5H-benzo[b]oxepin-4-ones 75 via Mitsunobu reaction of 2-benzyloxycarbonylamino-but-3-en-1-ol 71 with 2-iodophenol derivatives 54, palladium-catalyzed Heck coupling, and iodine(III)-mediated rearrangement under Koser and Justik conditions (Scheme 20). [67] The substituted benzo[b]oxepin-4-ones showed potent aminopeptidase (APN or CD13) inhibitory activity.…”

Recent advancements in synthetic methodologies of 3-substituted phthalides and their application in the total synthesis of biologically active natural products

“…Arcadi and co-workers 69 have described a palladiumcatalyzed hydroarylation and hydrovinylation reaction of gpropargylic alcohols 54 with aryl iodides 55 to afford crude g,gdisubstituted allylic alcohols 56. Allylic alcohols 56 were treated with NaOH followed by acidication afforded 3,3-disubstituted phthalides 59 in good to moderate yields (Scheme 3).…”

Synthesis and Antifungal Activity of 3-Aryl-7-methyl- 7-hydroxy-2-octen-6-olide

“…[3,[8][9][10][11][12][13] However, the natural products with sevenmembered lactone have rarely been reported and synthesized in the literatures (Figure 1, 1～4), [14][15][16][17][18][19][20][21][22] because they have a unique ring strain seven-membered lactone structure, and the synthesis of them is practically challenged. [23][24][25][26][27][28][29] In the previous paper, we paid our attention to the total synthesis of natural products with seven membered lactone moiety and their biological activities, the synthesis and biological activity evaluation of the racemic 3,7-dimethyl-7-hydroxy-2-octen-6-olide (1), 3,7-dimethyl-2,6-octadien-1,6-olide (2), 7-methyl-7-hydroxy-2-octen-6olide (5), and their 3-(2-hydroxypropan-2-yl)-4,5-dihydrobenzo[c]oxepin-1-(3H)-one analogues (6) were carried out in our laboratory. [30][31][32][33] 3-Phenyl-7-methyl-7-hydroxy-2octen-6-olide (5a, R＝Ph) was found to exhibit much excellent fungicidal activities against several phytopathogens than naturally occurring 3,7-dimethyl-7-hydroxy-2-octen-6-olide (1) and the other derivatives.…”