Synthesis of propellanes containing a bicyclo[2.2.2]octene unitviathe Diels–Alder reaction and ring-closing metathesis as key steps

Abstract

The synthesis of propellanes containing bicyclo[2.2.2]octene via olefin metathesis approach is less explored.Herein, we describe a simple and convenient method to synthesize propellane derivatives containing a bicyclo[2.2.2]octene unit which are structurally similar to 11b-HSD1 inhibitors by sequential usage of the Diels-Alder reaction, C-allylation and ring-closing metathesis (RCM) as the key steps. Additionally, we expanded this approach to an endo-tricyclo[4.2.2.0 2,5 ]decene derivative which is a useful monomer for polymer synthesis and we have also synthesized basketene and anthracene-based propellanes using the same strategy.

Application of New Efficient Hoveyda–Grubbs Catalysts Comprising an N→Ru Coordinate Bond in a Six-Membered Ring for the Synthesis of Natural Product-Like Cyclopenta[b]furo[2,3-c]pyrroles

“…However, it was found that the pure trans-isomers 6aA, 6eA and 6pA are able to form tricyclic systems of cyclopenta[b]furo[2,3-c]pyrrole 7 in the RRM reaction (the last column of Tables 2 and 4). Moreover, in contrast to the communications [9][10][11]17,19,21,22], in our case, the ring-rearrangement metathesis does not require the supporting application of ethylene that facilitates practical synthesis. To achieve the maximum yield of the target tricycles 7, the metathesis reaction was optimized in terms of solvent, temperature, duration and amount of catalyst.…”

“…It worth mentioning here that by revising the ethylene-supported transformations of the similar substrates [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ], the question of the sequence of metathesis stages arose. In theory, two paths exist for the rearrangement of 6 to 7 in an ethylene atmosphere: ROM/RCM, or vice versa, RCM/ROM successions [ 43 ].…”

“…2), with a shorter bond length between nitrogen and ruthenium (the N→Ru bond is 2.24 Å [27]), is stable at least up to 140 • C [27], and therefore turned out to be effective for the preparation of cyclopenta[b]furo [2,3-c]pyrrole 7p at temperatures above 100 • C in microwave-assisted experiments (entries 17-26, Table 4). It should be noted that the amount of catalysts 1 and 2 required for the complete conversion of the initial esters 6eA, 6pA did not exceed 0.5 mol % in both cases, while the reaction time was much shorter than in the papers cited above [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23].…”

“…In particular, the ring-rearrangement metathesis (RRM) of bi- and polycyclic alkenes has made it possible to obtain systems that are practically inaccessible by means of other synthetic pathways [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Most often, for the rearrangement of bridged alkenes, the commercially available Grubbs (G) and Hoveyda–Grubbs (HG) ruthenium catalysts are used, which permits the reliable production of scaffolds possessing a wide range of potential biological activity due to the characteristics of their carbon skeletons [ 19 , 20 , 21 , 22 , 23 ]. Representative examples of the above-mentioned metathesis reactions clearly demonstrate a variety of possible transformation routes that give the structural diversity of the available final products ( Scheme 1 ).…”

Design and Synthesis of Polycycles, Heterocycles, and Macrocycles via Strategic Utilization of Ring‐Closing Metathesis

“…We have also demonstrated an elegant strategy for the synthesis of propellanes 194 , 196 , and 199 from commercially available starting materials . To this end, the cycloaddition reaction of cyclooctatetraene 187 and maleic anhydride 188 gave the known cycloadduct 189 , which on condensation with aniline gave the N ‐phenyl derivative 191 .…”