Gold(I)-catalyzed Tandem Cyclization of 3-(tert-Butoxycarbonyloxy)-1,6-enynes

Abstract

Over the past decade, there has been explosive interest in the area of new homogeneous gold-catalyzed reactions.1 The capability of cationic gold(I) species that activates alkynes towards heteroatom and carbon nucleophiles led to the discovery of numerous novel catalytic transformations. Diverse structures generated by these reactions make this process a very powerful strategy for organic synthesis. Tandem reactions of 1,n-enyne substrates are particularly interesting in this regard.2 Our interest in this area has focused on the divergent reactivity of 3-alkoxy-1,6-enynes. A salient feature of these types of substrates is that oxygen atom and the olefin can compete in the addition to the gold-bound alkynes. This competition may lead to synthetically important structural motifs via catalytic tandem reactions.Recently, we discovered gold(I)-catalyzed cycloisomerization of 3-methoxy-1,6-enynes, invoking heterocyclization and the subsequent [3,3]-sigmatropic rearrangement as the key mechanism.3 Further investigation of 3-siloxy-1,6-enynes led to the development of unprecedented gold(I)-catalyzed divergence between pinacol-terminated vs. Claisen-terminated cyclization cascades. 4 These examples indeed illustrate that the reactivity of 3-alkoxy-1,6-enynes in the divergent pathway can be controlled by the subtle variation of the substituents on the alkoxy group. In an effort to expand the scope of the catalytic reactions associated with the 3-alkoxy-1,6-enynes, we pursued further variation of the alkoxy moiety. In particular, we considered using 3-(t-butyloxycarbonyl)oxy-1,6-enynes 1 (Scheme 1), based on the recent reports on the use of t-butyloxycarbonyl (t-Boc) group in gold(I)-catalyzed domino processes. 5 We first reasoned that the introduction of this substituent onto the oxygen would suppress the formation of 3 (path B, Scheme 2), because of the reduced bacisity of t-Boc group. Unlike our previous studies, 3,4 pathway A would prevail in this case. Moreover, this new catalytic reaction will provide synthetically useful cyclohexane-1,2-diol compounds possessing exo-olefins at the 4-position (2, in Scheme 1).Our rationalization in terms of the competing pathways was justified when we examined substrate 4. Using electron poor ligand 6a (5 mol%) with AgSbF6 (5 mol%) provided the product 5 in only 32% NMR yield, although the starting material was completely consumed within 10 min (entry 1). In this preliminary study, no apparent formation of the cycloheptene product 3 generated via path B was observed. Using a more electron-donating ligand 6b (5 mol%) somewhat improved the yield of 5 (entry 2). A significant increase of the yield arises when more electron-donating ligand 6c (5 mol%) was employed (entry 3) In this case, the product was obtained in 76% isolated yield after 10 min. Delightedly, reducing the catalyst loading to 2 mol% still maintained the catalytic activity with slight decrease in the yield of the desired transformation