Intermolecular reactions of gold( I )-carbenes with furans by related mechanisms †‡

The intermolecular gold( I )-catalyzed reactions of propargyl carboxylates, 1,6-enynes, or 7-substituted 1,3,5-cycloheptatrienes with furans a ﬀ ord cyclopentenones, polyenes or polycyclic compounds by related mechanisms initiated by the electrophilic addition of gold( I ) carbenes to furans followed by ring-opening.

Gold-catalyzed intramolecular cycloisomerization reactions of 1,n-enynes have been widely studied and applied in synthesis, 1,2 following the pioneering work on similar transformations catalyzed by other late transition metals. 3However, the development of mechanistically related intermolecular cyclizations of alkynes with alkenes or other substrates has been more challenging. 4n important transformation in this area is the cyclization of alkynylfurans, which was discovered using gold 5 or platinum 6 catalysts.This transformation leads to substituted phenols in a rather straightforward manner.Only one example of the corresponding gold-catalyzed intermolecular reaction of a furan with an alkyne had initially been reported using the binuclear gold(I) complex [(Ph 3 PAu) 2 Cl]BF 4 , 5f although we recently found that phenols can be obtained using air-stable [IPrAu(PhCN)]BAr F 4 (A) (BAr F 4 = 3,5-bis(trifluoromethyl)phenylborate) as the catalyst (Scheme 1). 7 have now found that propargyl carboxylates react differently with furans in the presence of gold(I) catalysts to give functionalized cyclopentenones or cyclopentadienyl carboxylates, which had not been reported before by related procedures (Scheme 2).Aryl gold(I) carbenes generated in enyne cyclizations 1n,2,8 or by retro-Buchner reaction 9,10 of 7-substituted 1,3,5-cycloheptatrienes also react with furans to give rise to polycyclic compounds.
The extent of stabilization of a carbocation by gold(I) has been the subject of discussion, [11][12][13] although, according to theoretical calculations, a carbene-like structure is favored when gold(I) is coordinated to strongly donating ligands such as N-heterocyclic carbenes and phosphines.
We first examined the reaction of propargylic acetate 1a with 2,5-dimethylfuran 2a in the presence of gold(I) catalysts, which in all cases gave rise diastereoselectively to cyclopentenone 3a (Table 1).The best yield of 3a was obtained using a cationic gold(I) catalyst [IPrAu(PhCN)]BAr F 4 (A) (Table 1, entry 1).Related IPr gold(I) complex B with hexafluoroantimonate anions gave slightly lower yield after 30 min (Table 1, entry 2), whereas neutral complex C and cationic IMes derivatives required longer reaction times (Table 1, entries 3 and 4).Phosphine and phosphite gold(I) catalysts were less reactive in this transformation (Table 1, entries 5-8).Poor results were obtained with AuCl 3 or PtCl 2 (Table 1, entries 9 and 10).
Unsymmetrically substituted furans 2c-d reacted with 1a and catalyst A to give a mixture of cyclopentenones 3i-j/3i′-j′ favoring formation of the regioisomer with the less sterically hindered group at C-3 of the cyclopentenone (Scheme 3).
We propose a mechanism for the formation of the cyclopentenones and cyclopentadienyl esters initiated by the 1,2acyloxy migration of η 2 -alkyne-gold(I) complex 5, 15    a Isolated yields.b 2.5 : 1 trans/cis.c 5 : 1 trans/cis.to form 9. Intermediate 9 could also be formed directly from 7 by 1,2-elimination.A Mukaiyama-Michael-type cyclization would then form 10, which leads to cyclopentenones 3 or cyclopentadienyl benzoates 4. The observed trans-stereoselectivity is presumably derived to the preferred Z-configuration of the vinyl gold(I) carbenes. 16In the case of unsymmetrically substituted furans 2c-d, the major regioisomers are formed by the attack of the less substituted site of the furan to intermediate 6.
Formation of open chain products derived from intermediates similar to 9 has been reported before for Ru(II), Pt(II), 17,18 and, in one case, for Au(I)- 19,20 catalyzed reactions of furans.A similar reactivity was observed in the reaction of furans with gold(I) carbenes generated by the ring opening of cyclopropenes. 21It is interesting that in our case, 2,5-disubstituted furans react preferentially at C-2, instead of at C3 as it is observed with Ru(II) as a catalyst. 17,6-Enynes 11a-b reacted with mono-and disubstituted furans 2a-j in the presence of gold(I) catalysts to form ketones or carboxylic acid derivatives 12a-i featuring a triene moiety with a (Z,Z)-configuration (Table 3).22 This transformation is mechanistically interesting as it features a gold(I)-catalyzed cyclization/1,5-OR migration via intermediates 13 and 14 to form α,β-unsaturated gold(I) carbenes 15, 8 which react with electron-rich furans to form 16 (Scheme 5).A similar elimination to that proposed before in the elimination of 7 (Scheme 4) gives 12a or 12d after hydrolytic cleavage of the trimethylsilyl ester.
In summary, we have found that three very different types of substrates react with furans and gold(I) catalysts under different reaction conditions by mechanistically related pathways.This is best rationalized if similar gold(I) carbenes are involved as intermediates in all these processes, which is also supported by DFT calculations.The fact that similar reactions are observed in transformations proceeding via ruthenium(II) or platinum(II) carbenes 17 further supports the involvement of closely similar species using gold(I) catalysts.These reactions of furans lead to rather elaborated products from readily available substrates under mild conditions.Further applications of  the trapping of reactive gold(I) carbenes with other types of nucleophiles are being explored.
followed by the electrophilic trapping of the α,β-unsaturated gold(I) carbene 6 by furan 2 (Scheme 4).The resulting intermediate 7 may lead to the cyclopropanation product 8, which could open
-type reaction would lead to intermediates such as 23 or 25, which affords open chain derivatives 24 or 21.In the former case, the initially formed 25 affords 20a-c by Z to E isomerization or 19a-b by a Michael-type ring closing.

Scheme 7
Scheme 7 Reaction of furans with gold(I) carbenes generated by retro-Buchner reaction.