Hoveyda-Grubbs II catalyst

In 2012, You and co-workers developed a cascade ring-closing metathesis/ isomerization/asymmetric Pictet-Spengler reaction, employing ruthenium complex (Hoveyda-Grubbs II catalyst) and chiral phosphoric acid as the... 

Previously, Ascic et al. [43] reported the same reaction with the Hoveyda-Grubbs II catalyst and trifluoroacetic acid as a bicatalytic system, but as a racemic version [43]. The intermediate acyliminium ion readily attacks also other tethered nucleophiles, such as trimethoxybenzene, benzothiophene, thiophene, 0,0-dimethyl catechol, and furan, intramolecularly. When tryptophane or the corresponding alanine derivatives are employed, reasonable levels of diastere-oselectivity can be observed for the terminal Pictet-Spengler acyhminium cyclization. Even a tethered alcohol functionahty diastereoselectively traps the chiral acyhminium intermediate, furnishing bicychc OAf-acetals. 

Mukai and coworkers reported the concise total synthesis of Melodinus alkaloid ( )-meloscine (40) [Route (a), Fig. 13], in which the final key transformation involved an alkene RCM of the triene precursor (42) in the presence of Hoveyda-Grubbs II catalyst [55], The RCM between the A(-allyl group and the top-oriented vinyl moiety exclusively occurred to generate the desired diastereomer (40) in almost quantitative yield. The extremely high diastereoselectivity could be rationalized on the basis of ring strain to favor one conformer. Shortly after this work, Curran et al. disclosed another approach to the total syntheses of ( )-epimeloscine (41) and ( )-meloscine (40) applying the same RCM protocol for the final ring formation [Route (b), Fig. 13] [56],... 

In terms of the application of selective alkene RCM for multiple ring formation, Martin et al. reported a very interesting example in their total synthesis of indole alkaloid ( )-pseudotabersonine (44) [57]. In this case, a highly functionalized tetraene substrate (45) underwent double RCMs in the presence of Hoveyda-Grubbs II catalyst to afford a mixture of two diastereomers (46) (Fig. 14). During this process the high regioselectivity for alkene RCM was achieved, which was worthy of note. 

Preparation of 6-alkylidenebicyclo[3.2.1]octan-8-one via a tandem cross-metathesis/ semipinacol rearrangement reaction occurs with the Hoveyda-Grubbs II catalyst that serves as the Lewis acid for the rearrangement (Scheme 92). ... 

A synthesis of enantioenriched tetrahydro- -carbolines has been reported using chiral phosphoric acid in conjunction with Hoveyda-Grubbs II catalyst through a ring-closing metathesis/isomerization/Pictet-Spengler cascade reaction (Scheme 93). ... 

Esterification of 56 using alcohol 53 (Scheme 6.12) with DCC/DMAP (dicyclo-hexylcarbodiimide) furnished ester 57, which on RCM with Gmbbs II catalyst in CH2CI2 afforded diastereomeric cyclic compound 58. Desilylation of 58 followed by oxidation and MOM deprotection gave alcohol Z-60 as identified from the spectral data. However, RCM of ester 57 under Hoveyda-Grubbs II conditions gave a mixture of separable macrolides 58 and 58a in 1 3 ratio. Lactone 58a, on further desilylation, oxidation, and deprotection, furnished balticolide 60 (Scheme 6.12). 

General aspects and new metathesis catalysts. For alkene metathesis Grubbs I (1) and Grubbs II (2, 3) complexes, and the Grubbs-Hoveyda catalyst (4A) and Grela catalyst (4B) remain the workhorses. 

II) first-generation Grubbs catalyst (III) second-generation Grubbs catalyst and (IV) second-generation Hoveyda-Grubbs catalyst (HG-II) [5]. 

Wang and co-workers at GlaxoSmithKline (London, U.K.) published RCM approaches for the preparation of potent cathepsin K inhibitor 18, a candidate for the treatment of osteoporosis and osteoarthritis.As shown in Scheme 24.6, the researchers prepared tetrahydroazepine 17 via the RCM of diene 16 using Hoveyda catalyst [Ru]-III in toluene. Under the optimized scale-up conditions, 17 was obtained in 96% yield (71.8 kg)." Although Grubbs catalyst [Ru]-II worked well in the small-scale RCM of 16, poor conversions were observed on scale-up. 

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