Gold(I)‐Catalyzed Synthesis of Functionalized Cyclopentadienes

Abstract

. ‥ or a touch of gold: Electrocyclization of the pentadienyl cation produced on coordination of cationic phosphinegold(I) to vinyl allenes results in the regioselective formation of highly functionalized cyclopentadienes. The regioselectivity of the reaction is consistent with an intramolecular 1,2-hydrogen shift of a gold(I)–carbenoid intermediate (see scheme). In light of our recent success in using [Ph3PAuCl] with AgSbF6 in dichloromethane for carbon–carbon bond-forming reactions,4c we chose this system for preliminary studies of the proposed cycloisomerization (Table 1). Treatment of vinyl allene 4 with 2 mol % cationic triphenylphosphinegold(I) afforded the desired cyclopentadiene 5 as a single regioisomer in 97 % yield after 1 min at 0 °C (Table 1, entry 1). Similar results were obtained when a lower temperature or lower catalyst loading were used (Table 1, entries 2 and 3). Control experiments employing either 5 mol % [Ph3PAuCl] or 5 mol % AgSbF6 as the sole catalyst did not lead to any conversion of 4 into 5 (Table 1, entries 4 and 5). Other transition-metal complexes showed no catalytic activity; however, gold(III) chloride rapidly consumed 4 to afford a small amount of 5 (Table 1, entry 6).8 Entry Catalyst T [°C] t [min] Yield [%][a] 1 2 % Ph3PAuCl/2 % AgSbF6 0 1 97 2 2 % Ph3PAuCl/2 % AgSbF6 −20 5 93 3 1 % Ph3PAuCl/1 % AgSbF6 0 1 96 4 5 % Ph3PAuCl 23 180 0[b] 5 5 % AgSbF6 0 5 0[c] 6 5 % AuCl3 0 5 30[d] With optimal conditions in hand, the scope of the gold(I)-catalyzed cycloisomerization of vinyl allenes was examined.9 We were pleased to find that the reaction allowed for the regiospecific synthesis of functionalized cyclopentadienes in high yields with a variety of substitution patterns (Table 2). Substitution at the allene terminus was well tolerated, encompassing linear alkyl (Table 2, entries 8 and 9), oxygenated (entries 3–7), secondary benzyl (entry 1), and phenyl substituents (entry 2). Notably, the gold(I)-catalyzed reaction can be easily carried out on a gram scale albeit with a slightly diminished yield (Table 2, entry 1). Furthermore, the stability of acid-labile protecting groups, such as tetrahydropyranyl (Table 2, entry 9) and silyl ethers (entries 3, 4, 6, and 7), isopropylidene acetal (entry 5), and an N-Boc amine (entry 6), is a testament to the mildness of the reaction conditions. Bicyclic cyclopentadienes are readily produced from the cycloisomerization of vinyl allenes containing cyclic alkenes (Table 2, entries 1–6). Additionally, the gold(I)-catalyzed reaction can be employed for the synthesis of cyclopentadienes with a quaternary carbon center (Table 2, entries 2 and 3). The use of a more electron-rich gold(I) complex, [tBu3PAuCl], as a catalyst gave improved yields for some vinyl allenes (Table 2, entries 5, 6, 8, and 9). For example, switching the gold catalyst from [Ph3PAuCl] to [tBu3PAuCl] resulted in an improved yield for the formation of cyclopentadiene 21 (Table 2, entry 8). Entry Vinyl allene Cyclopentadiene Yield [%][b] 1 6[c] 7[c] 98 (88)[d] 2 8 9 92 3 10 11 63 4 12 13 86 5 14[c] 15[c] 78[e] 6 16 17 53[e] 7 18 19 72 8 20: R=Bn 21 39 (78)[e] 9 22: R=THP 23 87[d] Proposed mechanism for gold(I)-catalyzed cyclopentadiene synthesis. In conclusion, we have developed a gold(I)-catalyzed cycloisomerization of vinyl allenes for the synthesis of cyclopentadienes. The mild reaction conditions of this gold(I)-catalyzed carbon–carbon bond-forming reaction provide a regiospecific method for the synthesis of highly functionalized cyclopentadienes, including tricyclic structures through a tandem cycloisomerization/ring-enlargement reaction sequence. Application of the gold(I)-catalyzed reaction to the preparation of optically active metallocenes and asymmetric catalysis is ongoing in our laboratory and will be reported in due course. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z604006_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.