Catalytic Intramolecular Addition of Metal Carbenes to Remote Furans

Abstract

Diazo esters and diazo ketones linked to a furan undergo catalytic intramolecular addition of an intermediate metal carbene to the remote furan to form diendiones with ring sizes up to 17. Regioselectivity is catalyst dependent with addition to either the more or less substituted double bond. The high product yields and absence of need for high dilution suggest that this methodology is general for macrocycle preparations.

Macrocycle Formation from Catalytic Metal Carbene Transformations

“…With 15, which upon diazo decomposition can undergo either addition to the carbon-carbon triple bond or addition to the aromatic ring, aromatic cycloaddition occurs exclusively when Rh 2 (MEOX) 4 The extent to which this macrocyclization process can be used for the preparation of large-ring esters can be seen in results from diazo decomposition of the diazoacetate 16 derived from triethylene glycol (Scheme 11). 25 Catalysis by Rh 2 (5S-MEPY) 4 gave only the product from C-H insertion (17) in high yield even though the use of the model carboxamidate, Rh 2 (cap) 4 , resulted in a mixture of products in which both 17 (major) and 19 (minor) were evident. In contrast, use of Cu(MeCN) 4 PF 6 gave mainly 18, and dirhodium(II) octanoate, Rh 2 (oct) 4 , and Rh 2 (OAc) 4 gave mainly ring-opened products 19.…”

Dirhodium(II) Carbenes : The Chiral Product Cascade

“…Doyle et al (1999d) -intramolecular addition to remote furans; Davies and Panaro (1999) -improved D 2 -symmetric dirhodium(II) tetraprolinate cyclopropanation catalysts; Doyle et al (2000) -macrocycle formation via intramolecular cyclopropanation.…”

A gold-catalyzed 1,2-acyloxy migration/intramolecular cyclopropanation/ring enlargement cascade: syntheses of medium-sized heterocycles

“…As reported by Doyle, the tandem cyclopropanation and ring-opening process gave a 14-membered 70 ring compound as a Z/E isomeric mixture in only 40% yield (Scheme 1, D). [11] Herein, we reported an intramolecular reaction of furan-ring at C5-position under gold catalysis, affording ten or eleven-membered heterocycles with a trans-double bond in high chemoselectivity and regioselectivity in up to 98% yield.…”

“…When either electron-withdrawing 30 or electron-donor groups were introduced on the benzene ring of R 2 , the reactions proceeded smoothly to give the corresponding products 2d-2h in moderate to excellent yields ( Table 2, entries 3-7). When R 2 were 1-naphthalenyl and 2-chlorophenyl groups, the reactions produced the desired products 2i and 2j in 20% and 35 45% yields, and the relatively low yields were probably due to the increased steric hindrance ( [10][11][12][13][14]. However, treatment of N-phenyl group (R 3 ) protected substrate under gold catalysis, the reaction became complex, presumably due to this phenyl ring could also take part in the reaction as that of furan ring (Table 2, entry 15).…”

“…Subsequent 1,2-acyloxy migration delivers gold carbene intermediate C. [12] Following a cyclopropanation at C4-40 and C5-positions of furan delivers intermediate syn-D and regenerates the catalyst. [11] The steric hindrance of aryl groups in intermediate C may cause the cyclopropanation exclusively taking place at C4-and C5-positions. Finally, the ring opening process of syn-D provides the desired product 2a.…”