Tandem ROM/RCM

The dendrobatid alkaloid 251F 213 (Figure 12.4) was isolated from the skin exudates of a Columbian dendrobatid poison frog, Minyobates bombetes [105]. The asymmetric total synthesis of this molecule has been reported by Aube and co-workers [106], The synthesis featured a Noyori-type three-component reaction to access an advanced bicyclopentenone intermediate, and also included a tandem ROM/RCM reaction sequence and a Schmidt rearrangement as key steps. 

Scheme 2.23 Tandem ROM/RCM process in the synthesis of 14-membered macrolides.

From an interest in the phelligridin G scaffold Cooper and Wright have reported a tandem ROM/RCM approach to oxaspirocycles (Scheme 68) [74]. The ROM/RCM reaction of readily available oxabicycle 262 using the Grubbs second-generation catalyst 229 resulted in the generation of spirocycle 263 in 50 % yield. 

PhiUips et al. designed the tandem RRM reaction of bicyclic compounds having two reactive sites in side chains to synthesize a tricyclic diterpenoid cyanthiwigin U 137, which is isolated from both fungal and marine sources (Scheme 24.35). The two-directional tandem ROM-RCM sequence of bicyclo[2.2.2]-octane 135 was catalyzed by [Ru]-II (20mol%) under the ethylene atmosphere, and transformations of tricyclic compound 136 completed a synthesis of this natural product in 17% overall yield in 12 steps. 

A concise asymmetric total synthesis of (+)-cyanthiwigin U (307) was reported by Phillips and Pfeiffer relying on the clever use of tandem metathesis of bi-cyclo[2.2.2]octenes (Scheme 1.56) [76]. The two-directional tandem ROM-RCM of compound 308, using catalyst [Ru]-II under an atmosphere of ethylene, simultaneously generated the cyclopentenone and the cycloheptenone rings of... 

Scheme 74 Synthesis of bis-dihydropyran fragment 380 of halichondrin by tandem ROM-double RCM of cyclopentene 379 [158]...

A type of ROM-RCM based tandem reaction was discovered by Lazarova al When various natural 16-membered macrolide antibiotics with a 1,3-diene unit in the marocyclic core (e.g., josamycin 422) were exposed to catalyst E (20mol%) in the presence of 1-hexene (2 equiv.), an ROM-RCM sequence occurred with excision of... 

In contrast to 52 (Scheme 12), diastereomer 55 (Scheme 13), because of its more exposed and highly reactive strained olefin, undergoes rapid polymerization in the presence of 4a. The less reactive Ru complex 56 [23] can however be used under an atmosphere of ethylene to effect a tandem ROM/CM to generate 57. The resulting triene can be induced to undergo Mo-catalyzed ARCM (5 mol % 4a) to afford optically pure 58, the AROM/RCM product that would be obtained from 55. 

The desymmetrization of dicarbonate 206 was initiated by the addition of one equivalent of N-(3-butenyl) nosylamide 207 under palladium catalysis in the presence of Trost s chiral diphosphine ligand 205. When the first allylic substitution was completed, the reaction was warmed and the resulting intermediate 208 was treated in situ with one equivalent of a second nosylamide 209. Product 210 resulting from this double substitution reaction was submitted to a tandem intramolecular ROM/RCM to furnish key precursor 211, which was engaged in the final cyc-lization step by the reduction of the double bonds, followed by the HCl-promoted domino deprotection of the acetal and aminal formation. 

The Blechert group also applied the tandem RRM process with CM (RCM-ROM-RCM sequence) to the synthesis of (—)-lasubine 11 (141, Scheme 24.36), an alkaloid extracted from the leaves of Lagerstroemia subcostata Koehne. ° This strategy requires a careful choice of substrates and catalysts to avoid the CM reaction before the RRM reaction takes place. Therefore, cyclopentenone 138 was chosen as a starting material from the outcome of their study. In the presence of [Ru]-II (5 mol%), the treatment... 

Another example of some of the problems associated with the use of RCM in the formation of medium rings comes from the Fujiwara et al. work on ciguatoxin [52]. The generation of the E-ring oxepine with the F-ring intact resulted in the generation of not only the desired product (228) but also a significant quantity of bis-oxepene 229 from a competitive ROM/RCM tandem sequence (Scheme 3.44). 

Treatment of the precursor 150 with Grabbs II catalyst (give structure of the catalyst in the scheme) initiated the key tandem ring-opening metathesis (ROM)/ring-closing metathesis (RCM) sequence, which led to the carbocyclic... 

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