Ring‐Rearrangement‐Metathesis Approach to Polycycles: Substrate‐Controlled Stereochemical Outcome During Grignard Addition

Abstract

A variety of structurally intricate polycycles have been assembled through ruthenium‐catalysed ring‐rearrangement metathesis of norbornene derivatives. The various substrates required for this work were prepared using Diels–Alder reactions and Grignard additions as key steps. Enyne ring‐rearrangement metathesis of a norbornene system containing a propargyl moiety produced a 1,3‐diene; this was then treated with an appropriate dienophile to deliver the corresponding cycloaddition product.

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

“…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].…”

“…The discovery of metathesis reactions has allowed the noticeable expansion of possibilities for the transformation of different unsaturated substrates, including those aimed at obtaining complex naturally occurring compounds and pharmacologically meaningful molecules, which is reflected in a number of recent reviews [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. 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 ].…”

Selectivity in Ring‐Closing Metathesis: Synthesis of Propellanes and Angular Aza‐tricycles

“…Our journey commenced with Fischer indolization, of 2‐allylcyclohexanone 1 with phenylhydrazine hydrochloride salts 2 a – j under N , N ′‐dimethylurea:L‐(+)‐tartaric acid (DMU:TA) eutectic melt to produce indolenine derivatives 3 a – j in 74–90% yields. Subsequently, indolenine 3 a was treated with allyl magnesium bromide in THF (or diethyl ether). The expected product 4 a was not observed and the starting material was recovered.…”

Six-Membered Ring Systems

“…Certain reaction types have merited special attention. Ring-closing metathesis was applied to the synthesis of 3,6-dihydro-2H-pyrans starting from diene and enyne skeletons using Grubbs catalysts (16TA954,16EJO3900) and also to construct the 5,6-dihydropyran-2-one ring in many natural compounds including cryptocaryol (16AGE5049), cryptomoscatone D1 and (5R,7S)-kurzilactone (16TL1087), the C1-C27 subunit of hemicalide (16JOC11275), 12 withanolide analogs (16S48), and in the synthesis of eight pure stereoisomers of pironetin-dumetorine hybrids, a new scaffold for tubulin binders (16EJO2029). Prins cyclization was used to build the tetrahydropyran core of four diarylheptanoids from Dioscorea villosa (16TL3505), while oxa-Michael cyclization reactions were used to prepare the tetrahydropyran rings of (−)-gilbertine (16JOC4566), neopeltolide (16JOC415), rhopaloic acid A (16AGE3455), and fragments of various polyketides (16AGE6280).…”