Grubbs diastereoselectivity

Allylboronates are attractive reagents for the highly diastereoselective ally-lation of carbonyl compounds. A sequential cross-metathesis-allylation reaction has recently been developed by Grubbs et al. [88c] and by Miyaura et al. [103]. The sequence is illustrated in Scheme 23 for the formation of homoallylic alcohol 114 from allylboronate 112, acetal 113, and benzaldehyde [88c]. 

Representatives of the bridged sulfone system 70 have been subjected to ruthenium catalysed ring-closing metathesis reactions (Grubbs catalyst) and shown to afford, in low yields, a few selected cyclic dimers and trimers, of all the possibilities available. The diastereoselectivities observed were rationalised in terms of kinetic control involved with internal ruthenium/sulfonyl oxygen coordination . 

The aryl radical cyclization has been successfully used for the preparation of substituted dihydrobenzo[Z)]indoline derivatives [59], An example is shown in Reaction (7.49). The diene 42 was preliminarly subjected to ring-closure metathesis using Grubbs catalyst and then treated with (TMS)3SiH and EtsB at -20 °C, in the presence of air, to provide the compound 43 with an excellent diastereoselectivity. 

Unsaturated sulfonates e.g. 72 undergo a RCM using a second generation Grubbs catalyst 9 to give 5,6-dihydro-l,2-oxathiine 2,2-dioxides. The 5,6-dihydro derivative behaves as a dienophile towards cyclohexa-1,3-diene, giving the endo sultone with complete diastereoselectivity <04S1696>. 

Recent efforts have achieved Z-selective ruthenium carbene catalysts, providing a catalyst solution to a general problem in stereoselective alkene synthesis Diastereoselectivity in Olefin Metathesis Development of Z-Selective Ru Catalysts Vol 1, Chapter 3 Grubbs, Handbook of Metathesis, 2nd Edition, Volume 2, Chapter 7. As this is a relatively new field, mechanistic studies are... 

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. 

Grubbs catalyst afforded tricyclic [7.5.6] and [7.6.6] ring systems as single diastere-omers in moderate to good yields. Since no specific structural feature in the substrates was found responsible for the observed diastereoselectivity, the authors assumed the RRM process occurs under kinetic control. 

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],... 

An interesting approach to imino sugars was presented by Behr and coworkers/ Using an indium-mediated allylation of a carbonyl group in the unprotected pentosylamines such as 194, they prepared the linear diene 195 with very high diastereoselectivity dr> 95 5 Scheme 40). The latter compound was then in situ protected with p-toluenesulfonic acid (as ammonium salt) and subjected to the RCM reaction with the Hoveyda-Grubbs II cat. which afforded derivative 196 with a long, poly-hydrojylated side-chain. 

CM reactions with vinyl boronates were first reported by Morril and Grubbs [16]. They are usually diastereoselective in favor of the E-isomer. Vincent and Prunet used this type of CM for the synthesis of the C1-C15 fragment of dolabelide C, a cytotoxic macrolactone isolated from the sea hare Dolabdla auricularia [17]. Hence, 1,1-disubstituted olefin 28 was reacted with 4 equiv. of vinyl boronate 29, and the resulting product was converted to the corresponding vinyl iodide in 89% yield for the two steps (Scheme 10.8). As it is often the case with 1,1-disubstituted... 

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