A Scalable, One-Pot Synthesis of 1,2,3,4,5-Pentacarbomethoxycyclopentadiene

Abstract

1,2,3,4,5-Pentacarbomethoxycyclopentadiene (PCCP) is a strong organic acid and a precursor to useful organocatalysts, including chiral Brønsted acids and silicon-based Lewis acids. The synthetic route to PCCP, first reported in 1942, is inconvenient for a number of reasons. The two-step synthesis requires the purification of intermediates from intractable side-products, high reaction temperatures, and extensive labor (3 days). We have developed an improved procedure that delivers PCCP efficiently in 24 hours in one pot at ambient temperature and without isolation.

Unified Synthesis of Polycyclic Alkaloids by Complementary Carbonyl Activation**

“…[1] Their diverse scaffolds with hydrogen bond donor and acceptor groups positioned in a well-defined spatial arrangement make them attractive starting points and inspiration for drug development. [2] Bioactive polycyclic alkaloids, such as yohimbine (1), hirsutine (2), deplancheine (3), eburnamonine (4), ilicifoline B (5), peganumine A (6), and reserpine (7), contain the common quinolizidine core I fused to different heterocyclic rings (Figure 1). We reasoned that developing a straightforward annulation method for efficient construction of these scaffolds is beneficial for the total synthesis of polycyclic natural products and their analogs.…”

“…We tested different conditions to achieve selective amide activation via reactive nitrilium ions, [3] including a variety of phosphorus (V) reagents frequently applied in the Bischler-Napieralski reaction [5] and the von Braun amide degradation (Table 1, entries 1-4). [6] We also screened strong electrophiles, such as Me 3 SiCl and (COCl) 2 , [7] and the Tf 2 O / 2-chloropyridine system [8] which have been used successfully in electrophilic amide activation recently (Table 1, entries 5-7). Most of these conditions afforded tricyclic imine 9 as the major product.…”

Enantioselective PCCP Brønsted Acid Catalyzed Aminalization of Aldehydes

“…18 Regarding the above-mentioned strategies involving chiral Brønsted acids, we envisioned that chiral pentacarboxycyclopentadiene (PCCP) derivatives could be used in enantioselective aminalization of aldehydes with anthranilamide derivatives. PCCPs were firstly reported by Otto Diels, 29,30 but recently, Lambert and co-workers introduced a new generation, chiral PCCPs (Figure 1). 29 Due to the high stability of aromatic cyclopentadienyl anion, PCCPs exhibit a low degree of pKa comparable to pKa of phosphoric acids.…”

“…Contrary to chiral phosphoric acids, PCCPs offer less laborious and inexpensive preparation protocol 30,31 , which makes them an interesting alternative in chiral Brønsted acid-catalyzed transformations. 29,[32][33][34][35] Results and discussion: Table 1: Optimization of reaction condition for aminalization between 1a and 2a.…”

Controlled Cationic Polymerization: Single-Component Initiation under Ambient Conditions

“…Specifically, we propose that the propagating chain end would exist as an equilibrium between the cyclopentadienyloxocarbenium salt 2 and the covalent species 3 (Figure 1b), and that addition of monomers to 2 would occur via the transition state depicted in Figure 1c. 25,26 Given the reactive nature of the oxocarbenium ion, we speculate that the chain end would exist primarily in the covalent form and provide controlled polymerization at ambient temperature. This proposed mechanism would eliminate the need for highly purified reagents, an inert atmosphere in order to exclude moisture, and low temperature conditions.…”