Bridged benzocyclotrimers: concepts, synthesis, and applications

: Bridged polycyclic frameworks represent a unique tool to form curved units, the bicyclo[2.2.1]hepta-2,5-diene system being widely exploited to design and induce concave topologies. In particular, bridged benzocyclotrimers (BCTs) are characterized by a flat aromatic base decorated with bridged polycyclic motifs which provide the suitable curvature underlying the concave-convex topology. In the 1960s, these molecules attracted interest for their own chemical and physical properties. Later, the improvements of synthetic procedures to produce bridged BCTs have paved the way for their utilization to design and prepare molecular containers, bowls, cages, and baskets that are able to accommodate target molecules, recognize them, and modulate their functions. In this frame, we aim to describe the historical evolution of the concept, from the first bridged BCTs explored to confirm the existence of strained alkynes, and the phenomenon of bond alternation (Mills-Nixon hypothesis), to the most recent gated molecular baskets developed as dynamic synthetic receptors for molecular delivery. The main synthetic approaches which have been used to perform cyclotrimerization of bridged polycyclic alkenes, and related mechanisms, are also examined and discussed, with a specific focus on the syn/anti stereoselectivity issue and its consequences at a mechanistic level. The present review covers literature contributions published until mid 2021.

Branched 2-amino-1,3-dicyanocyclopenta-1,3-diene

Reaction of 2-chloroisobutyrophenonewith two equivalents of malononitrile anion furnishes 2-amino-1,3-dicyano-5,5-dimethyl-4-phenylcyclopenta-1,3-diene. The cyclic compound represents the novel 2-amino-1,3-dicyanocyclopentadiene structure. The unique 1-cyano-2-amino-3-cyano arrangement in the cyclopentadiene brings about a strong polarization of the electronic configuration of the diene system that is conformed by two opposite dipolar halves. The polarized electronic configuration accounts for the extreme persistence manifested by the cyclopentadiene. The compound owns a vivid lemon-hued yellow color consequent to an unusually intense n ®p*absorption of a cyano group in the extensively conjugated compound. This is built up by consecutive one-pot reaction of two molecules of malononitrile carbanion and the ketonic substrate followed by a new tandem carbon-carbon cyclization with final elimination of cyanate ion.

HYDROBORATION-OXIDATION OF GLYCIRRETHIC ACID’S DERIVATIVES

The hydroboration-oxidation reaction is widely used in the chemistry of terpenoids both for proving the structure of new compounds isolated from natural raw materials and for the directed synthesis of low molecular weight bioregulators. Moreover, most of the known examples affect mono- and sesquiterpenes, a much smaller number - for di- and triterpenoids: most are represented by hydroboration-oxidation of localized double bonds, examples for conjugated dienes are limited only by hydroboration-oxidation of cis-eudesma-6,11-diene, abietic acid and its methyl ester. We found that the reduction of the pentacyclic triterpenoid – glycyrrhetate methyl ester – diisobutylaluminium hydride in methylene chloride at -78 ° С and subsequent hydrolysis in the presence of ammonium chloride proceeds with the formation of 3β,30-dihydroxy-18βH-olean-9(11),12(13)-diene with a yield of 90%. It was shown that the hydroboration of the 1,3-diene system in it with a 3.3 molar excess of diborane in tetrahydrofuran is accompanied by the restoration of the carboxyl function, and after oxidation with the hydrogen peroxide-sodium acetate system of the organoboranes formed, three alcohols are mixed (2 : 1 : 1): 3β,11,30-trihydroxy-18βH-olean-12(13)-ene, 3β,12,30-trihydroxy-18βH-olean-9(11)-ene and 3β,9,30-trihydroxy-18βH-olean-12 (13)-ene, respectively. A similar mixture of triols was also obtained by hydroboration-oxidation of 3β-hydroxy-18βH-olean-9(11),12(13)-diene-30-oic acid. The hydroboration-oxidation reactions of 3β,30-dihydroxy-18βH-olean-9(11),12(13)-diene or the corresponding 30th acid proceed as monoprocesses predominantly at 9(11) double bonds.

Synthesis of the C1–C9, C11–C19 Pyran Core and C19–C24 Fragments­ of Macrolactin 3

We describe herein an efficient synthesis of the C1–C9, C11–C19 pyran moiety and C18–C24 core fragments of macrolactin 3. The prominent features of this work include construction of the Z-double bond of the 1,3-(Z,E)-diene system utilizing Horner–Wadsworth–Emmons­ reaction under Still–Gennari conditions. A Sharpless asymmetric epoxidation and subsequent epoxide opening under BF3·OEt2 conditions were applied to generate the stereogenic centers at C15 and C16, oxa-Michael addition and Jacobsen resolution facilitate the synthesis of the fragments.

Total syntheses of smenothiazoles A and B

Stereocontrolled installation of vinyl chloride and the 2,5-diene system via silastannation, Stille reaction and desilylchlorination, and the final peptide coupling reactions led to the concise total synthesis of smenothiazoles A (1) and B (2).