Note Cite This: J. Org. Chem. 2018, 83, 12897−12902
pubs.acs.org/joc
Direct Synthesis of a Dioxabenzobicyclo[3.2.1]octane Core from Salicylaldehydes Haiyong Zhu,†,§ Chao Chen,‡,§ Dan Li,† Pengxin Wang,† Yuan Wang,† Lutao Bai,† Dongxu Yang,*,† and Linqing Wang*,† †
Downloaded via UNIV OF TEXAS AT EL PASO on October 19, 2018 at 08:14:36 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China ‡ Guangdong Provincial Key Laboratory of Nano-Micro Materials Research, School of Chemical Biology & Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China S Supporting Information *
ABSTRACT: A copper(II) trifluoromethanesulfonate via Prins reaction between salicylaldehydes and allyl alcohols is realized under mild conditions. A series of compounds containing dioxabenzobicyclo[3.2.1]octane motifs are obtained in moderate to good yields. The current method can efficiently construct the valuable structural motif from easily accessed starting materials, providing a smooth method to build benzobicyclo skeletons.
D
Scheme 1. Copper-Mediated Building of Different Dioxabenzobicyclo[3.2.1]octane Compounds
ioxabicyclo[3.2.1]octane skeletons can be found as a central structure in some natural products and bioactive compounds.1 Therefore, efficient methods would be valuable that provide access to these structural motifs from easily accessed starting materials under mild conditions.2 Although there are several works to efficiently build dioxabicyclo[3.2.1]octane motifs by different strategies, the studies toward dioxabenzobicyclo[3.2.1]octane structures are still limited. In 2000, Suga et al. constructed the benzobycyclo structure from a designed o-(methoxycarbonyl)diazoacetophenone substrate employing a bimetal catalysis.3 In 2002, Zammattio and co-workers synthesized a series of dioxabenzobicyclo[3.2.1]octane compounds by preparing phenolic epoxides as precursors.4 Ma’s group also accomplished this skeleton by Pd-mediated allene chemistry.5 Bochet et al. successfully built the benzobicyclo skeleton by photochemistry of allenyl salicylaldehydes in 2008.6 Very recently, Chang and co-workers reported a Cu/ DMSO-mediated intramolecular cycloacetalization/ketalization of o-carbonyl allylbenzenes for successfully constructing dioxabenzobicyclo[3.2.1]octane structures in good chemical yields (Scheme 1a).7 Inspired by the rapid development of Prins-type reactions under Lewis acid or Brϕnsted acid conditions,8,9 we describe a Cu(II)-catalyzed Prins reaction to build a different dioxabenzobicyclo[3.2.1]octane skeleton from salicylaldehydes and allyl alcohols under mild conditions (Scheme 1b). Although there are many documented methods on the development of Prins reactions, the application of salicylaldehydes in Prins reactions is still very limited.10 We initially tested the model reaction between salicylaldehyde 1a and allyl alcohol 2a by screening a series of Lewis acids. The desired product 3a was detected in the presence of BF3·Et2O, TMSOTf, BBr3, Cu(OTf)2, Sc(OTf)3, and Y(OTf)3, as shown in Table 1. Under mild conditions, the employment © 2018 American Chemical Society
of Cu(OTf)2 shows relatively better results, leading to bicycle product 3a in about 34% yield (Table 1, entry 6). Next we further optimized the reaction conditions by choosing copper(II) trifluoromethanesulfonate as catalyst (Table 2). The solvent screening process identified chloroform as an optimal choice compared with DCM, DCE, toluene, and tetrahydrofuran (Table 2, entries 1−5). Moreover, increasing the temperature to 30 °C leads to a slightly higher chemical yield of 3a (Table 2, entry 6). The introduction of some additives, such as molecular sieves, Na2CO3, or neutral aluminum oxide, would depress the reaction progress (Table 2, entries 7−9). To further improve the results of this reaction, we increased Received: July 22, 2018 Published: September 20, 2018 12897
DOI: 10.1021/acs.joc.8b01873 J. Org. Chem. 2018, 83, 12897−12902
Note
The Journal of Organic Chemistry
Scheme 2. Substrate Scope with Respect to Allyl Alcoholsa
Table 1. Optimization Process of the Reaction by Screening of Metal Catalysts
entrya
catalysts
yield of 3a (%)b
1 2 3 4 5 6 7 8 9 10
BF3·Et2O AlCl3 TMSOTf BBr3 ZnCl2 Cu(OTf)2 Mg(OTf)2 Ni(ClO4)2·6H2O Sc(OTf)3 Y(OTf)3
26 28
