Kinetically Controlled Ring‐Closing Metathesis: Synthesis of a Potential Scaffold for 12‐Membered Salicylic Macrolides

Abstract

For the synthesis of a 12-membered salicylic macrolide scaffold, ring-closing metathesis (RCM) of a omega-diene compound was planned. The stereochemical outcome of the RCM reaction changed depending on the type of Ru catalyst that was used; a "first-generation" Grubbs catalyst produced exclusively the E isomer and "second-generation" catalysts provided a mixture of the E and Z isomers under kinetic control (not thermodynamic control). Considerations for the E/Z selectivity are described.

Chemoselective olefin metathesis transformations mediated by ruthenium complexes

“…Recently, Matsuya and Nemoto investigated the formation of 12-membered Salicyclic macrolides via macro-RCM mediated by complexes Cat-1A, Cat-1C, and Cat-3C. 39 Unprotected diene 26 and protected phenol, such as the tert-butyldimetylsilyl ether 27, were used as substrates; results are summarized in Table 2. On both dienes, Cat-1A promoted the formation of the E isomer exclusively, respectively (E)-28 and (E)-29.…”

Neighbor‐directed histidine N (τ)–alkylation: A route to imidazolium‐containing phosphopeptide macrocycles

“…Because cyclization under RCM conditions typically yields mixtures of E/Z products, we eliminated geometric isomers by reducing the ring‐closing double bonds. We examined diimine reduction, since this is compatible with both solution and solid‐support protocols .…”

Synthesis of dicarba-cyclooctapeptide Somatostatin analogs by conventional and MW-assisted RCM: A study about the impact of the configuration at C α of selected amino acids

“…Moreover, it is also in accordance with the behavior of the 2 nd generation Grubbs catalysts and with the large ring size of our compounds. 44,45,46,47,48 However, recently Riera et al published the MW supported synthesis of the first dicarba-analogue of SRIF-14. 49 The authors claimed that in the RCM conditions very similar to those we used, the Z-isomer was by far the major species obtained despite the fact that the dicarba-SRIF-cycle is larger than our cyclo-octapeptides and contains the same aromatic side-chains pattern in positions 6-11 of the compounds I-XIII here described.…”