Gold-catalyzed intermolecular [4C+3C] cycloaddition reactions

Abstract

In the presence of the N-heterocyclic carbene gold catalyst (NHC-AuIPr, 7), propargyl esters 1a-f and 13 undergo a [4C + 3C] cycloaddition reaction with cyclopentadiene and furan under mild conditions. The evidence suggests the formation of the seven-membered ring occurs by a direct cycloaddition process, rather than a stepwise cyclopropanation/Cope rearrangement sequence.The potent antiangiogenesis natural product family of cortistatins contain a center sevenmembered ring flanked by two six-membered rings. 1,2 Our initial attempt to construct the tetracyclic ring system using a transannular [4C+3C] cycloaddition strategy was met with mixed results. 3,4 In the same time, Mascarenas and co-workers reported an intramolecular [4C +3C] cycloaddition reaction, in which an allene functional group was selectively activated by Pt or Au catalyst. 5 This type of allene-diene intramolecular [4C+3C] cycloaddition reactions was further improved to occur under milder conditions. 6-8 Other reports using propargyl esters as reactants involved stepwise [4+3] cycloaddition reactions to prepare benzonorcaradienes and azepines. 9,10 More recently, Harmata reported the treatment of 5-silyloxydioxins with 5 mol % AuCl 3 /AgSbF 6 in the presence of cyclopentadiene or furan resulted in the formation of [4C+3C]-cycloadducts. 11 In this report, we disclose an intermolecular version of goldcatalyzed formal [4C+3C] cycloaddition reactions. This discovery expands the employment of propargyl esters as precursors in gold-catalyzed [4+3] cycloaddition reactions. 12 The likely mechanism for our recently reported gold-catalyzed transannular [4+3] cycloaddition could involve two possible pathways based on known examples in the literature. [13][14][15] The first pathway involves a gold-stabilized allyl cation and the second involves a gold carbene intermediate. As shown in Scheme 1, the first pathway (I to II through A and B) includes (1) a 3,3-rearrangement of the propargyl ester to give an allenyl ester (A), 16,17 (2) in situ activation by the same gold catalyst to generate an allyl cation B ,18 and (3) a [4+3] cycloaddition followed by a 1,2-acetoxy migration and deauration to produce the tetracyclic ring system II. The second mechanism through intermediates C and D is depicted on the right side in Scheme 1. This pathway involves a 1,2-acetoxy migration followed by a cyclopropanation/Cope rearrangement to produce the same product. Diazoesters undergo cyclopropanation/Cope rearrangement reactions in the presence of rhodium catalysts and Davies and coworkers have studied these reactions extensively. 19,20 Ohe and coworkers reported cyclopropanation of alkenes using propargylic carboxylates as vinylcarbene precursors and [RuCl 2 (CO) 3 ] 2 as the catalyst. 21 More recently, Au(I)-catalyzed Correspondence to: Benjamin W. Gung. Supplementary data Supplementary data associated with this article (experimental procedures, NMR spectra) can be found in the online version at Publisher's Disclaimer: This is a PDF file of an unedited manuscript that...

Gold‐Catalyzed Tandem Cycloisomerization/Cope Rearrangement: An Efficient Access to the Hydroazulenic Motif

“…From a mechanistic point of view, it is important to note that, in contradistinction to what has previously been reported [Eq. (6)],9a,b, 2i the present tandem cycloisomerization/Cope rearrangement does not involve the initial formation of a gold carbenoid of type 24 which could be trapped by a diene to furnish the intermediate divinylcyclopropane 25 (compare 6 and 24 ). This is a key difference with earlier work.…”

“…2e More recently, electrophilic platimum(II) and gold(I) species have also shown their catalytic potential to produce 1 by a [4+3] cycloaddition between an allene and a diene [Eq. (1)] 2f–i …”

Gold‐Catalyzed Cyclopenta‐ and Cycloheptannulation Cascades: A Stereocontrolled Approach to the Scaffold of Frondosins A and B

“…[17] In contrast, when 1,4-dienes are used, the cyclopropyl system undergoes a goldcatalyzed Cope rearrangement to deliver the cis-2,3-disubstituted cycloheptenyl acetates 4 (Scheme 2; path b). [11] A boatlike transition state is proposed in this case to account for the observed cis relative stereochemistry.…”

“…[10] We envisioned that a reaction sequence involving propargyl esters and dienes could be orchestrated such that gold not only catalyzed the 1,2-acetoxy migration and subsequent cyclopropanation, but could also reactivate the in situ generated vinyl acetate, thereby triggering a formal homo-Cope rearrangement to give sevenmembered rings in a straightforward manner (Scheme 1; path a). [11] Furthermore, if alkenes instead of dienes were used, highly substituted cyclopentenyl acetates could be obtained upon cyclopropyl ring opening (Scheme 1; path b). Herein, we report the realization of these concepts and an application in the formal enantioselective synthesis of marine secondary metabolites frondosins A and B.…”

Gold(I)-catalyzed enantioselective cycloaddition reactions

“…However, significant progress has been made in the last 4 years. While the development of an intermolecular [4 + 3] cycloaddition between allenes and dienes remains elusive, neither in a racemic nor enantioselective fashion [69], it has been shown that allenamides [70] or allenyl ethers [71] participate as two-carbon atom components in several gold-catalyzed [4 + 2] cycloadditions with dienes. The racemic version of the reaction between allenamides and dienes, which is efficiently promoted by AuCl or the cationic gold catalyst Au9 /AgSbF 6 , was translated into a enantioselective version by using a novel chiral gold complex Au14 , featuring a triazole unit embedded in a rigid axially chiral cyclic frame (Scheme 11) [72].…”