Z-Selective olefinations

Perlmutter used an oxymercuration/demercuration of a y-hydroxy alkene as the key transformation in an enantioselective synthesis of the C(8 ) epimeric smaller fragment of lb (and many more pamamycin homologs cf. Fig. 1) [36]. Preparation of substrate 164 for the crucial cyclization event commenced with silylation and reduction of hydroxy ester 158 (85-89% ee) [37] to give aldehyde 159, which was converted to alkenal 162 by (Z)-selective olefination with ylide 160 (dr=89 l 1) and another diisobutylaluminum hydride reduction (Scheme 22). An Oppolzer aldol reaction with boron enolate 163 then provided 164 as the major product. Upon successive treatment of 164 with mercury(II) acetate and sodium chloride, organomercurial compound 165 and a second minor diastereomer (dr=6 l) were formed, which could be easily separated. Reductive demercuration, hydrolytic cleavage of the chiral auxiliary, methyl ester formation, and desilylation eventually led to 166, the C(8 ) epimer of the... 

The starting material is an O-protected a-hydroxyaldehyde which is submitted to an (E)- or (Z)-selective olefination. After O-deprotection, the allylic alcohol is rearranged to the y.d-un-saturaled ethyl ester with >99% chirality transfer. 

The stereoselectivity of olefin formation is crucial to the utility of CM. To date, a general metathesis catalyst capable of effecting diastereomeric control over a broad range of substrates has yet to be realized. Of particular interest is the development of a Z-selective catalyst, as Z olefins are a prevalent structural motif within both natural products and pharmaceutical agents.Current examples of Z-selective olefin CM have proved to be substrate dependent. These include the CM of enynes with alkenes, acrylonitrile the CM reaction... 

A highly Z-selective olefination of a-oxy and a-amino ketones via ynolate anions has been reported (Scheme 9).43 The stereocontrol mechanism has been explained by (g) orbital interactions between the s orbital of the breaking C-O bond or n orbital of the enolate and the s orbital of the C-O or C-N bonds of the substituent in the ring opening of the /I-lactone enolate intermediates, and/or the chelation to lithium. 

Z)-Alcohol 9 was therefore synthesized by (Z)-selective olefination of 13 with Ando s reagent 15, giving 16. 3H- and 13C-NMR spectra of synthetic (R,Z) 9 and (S,Z) 9 (both mixtures of diastereomers of C-l and C-5 ) were very similar to those of the natural pheromone, and (f ,Z)-9 was pheromonally active against E. leivisi.13 Mori s synthesis, however, could not determine the relative configuration at C-l and C-5 of the pheromone. 

This review will focus on isolated and characterized high-oxidation state molybdenum and tungsten alkylidene and metallacyclobutane complexes. Attention will be directed largely toward monoalkoxide pyrrolide (MAP) complexes because they have yielded the majority of new results in the last several years. MAP species have been found to be especially efficient in several Z-selective olefin metathesis reactions, such as homocoupling, cross-coupling, ethenolysis, and ROMP (see Grubbs, Handbook of Metathesis, 2nd Edition, Volume 2, Chapter 7). Most of what is presented here has appeared since a review in 2009 [4]. 

Flook, M. (2011) Z-Selective Olefin Metathesis Processes and O s/Syndioselective ROMP with High Oxidation State Molybdenum Alkyli-denes. PhD thesis. Massachusetts Institute of Technology. 

Keitz BK, Endo K, Patel PR, Herbert MB, Grubbs RH. Improved Ruthenium Catalysts for Z-Selective Olefin Metathesis. J dm Chem Soc. 2011 134(l) 693-699. 

Scheme 5.3 General pathway for Z-selective olefin metathesis with molybdenum alkyli-dene catalysts.

The importance of the cation-oxygen interaction has also been pointed out in highly Z-selective olefination reactions of the a-silyl-a-phosphoryl carbanion 19 (Scheme 2.16) [41, 42]. The chelating Li-O interactions are likely to determine the configuration of the carbanion 19 in the approach of the aldehyde. This transition state leads to the formation of the kinetically favored adducts 20, which give the (Z)-alkenes 21 after syn-elimination of the oxophilic silylated moiety and hydrolysis. 

Accordingly, considerable effort has been dedicated to the development of olefin metathesis catalysts exhibiting kinetic selectivity. As a result, a number of Z-selective tungsten-, molybdenum-, and ruthenium-based olefin metathesis catalysts have been recently developed (For Mo- and W-based Z-selective catalysts [24-41], For Ru-based Z-selective catalysts [42-45], For cyclometalated Ru-based Z-selective catalysts [46-58]). Many of these systems exhibit consistently high levels of activity and selectivity across a broad range of substrates. Herein, we will focus specifically on the cyclometalated ruthenium-based catalysts developed in our laboratory [46-58]. This chapter is intended to provide a comprehensive summary of the evolution of these cyclometalated ruthenium catalysts, from their initial serendipitous discovery to their recent applications in Z-selective olefin metathesis transformations. Current mechanistic hypotheses and limitations, as well as future directions, will also be discussed. 

Following the promising results obtained with 6 in preliminary Z-selective olefin metathesis assays [46, 47], a variety of new cyclometalated complexes were... 

Initial attempts to introduce other cyclometalated substituents or bulkier orthosubstituents on the A-aryl group only led to decomposition of the catalyst [48, 73]. Fortunately, replacement of silver pivalate with sodium pivalate allowed for a milder protocol to prepare previously inaccessible catalysts (e.g., 10 and 11) [52, 55]. With the exception of catalysts lacking ort/jo-substitution on the A-aryl ring (e.g., 13) [73], a variety of A-aryl and cyclometalated substituents were accommodated (Fig. 2). When these new catalysts were assayed in homo-CM reactions, a dramatic improvement was noted for catalyst 10, which exhibited TONs approaching 7,400 and near perfect Z-selectivity (>95%) [52]. This represents the highest catalytic efficiency exhibited by a Z-selective olefin metathesis catalyst reported to date. Catalyst 10 maintained remarkable activity and Z-selectivity in a variety of homodimerization reactions, as well as a selection of more complicated RCM and CM reactions (cf. Sect. 3). 

The abovementioned cyclometalated ruthenium catalysts have been applied in a number of Z-selective olefin metathesis reactions [46-58]. Of these catalysts, 10 remains the state of the art with respect to a general Z-selective catalyst for CM (Sect. 3.1) and mRCM (Sect. 3.3). The potential of 10 remains to be fully evaluated in more specialized transformations such as AROCM (Sect. 3.2), Z-selective ethenolysis (Sect. 3.5), or ROMP (Sect. 3.4). 

Cyclometalated Ruthenium Alkylidene Complexes A Powerful Family of Z-Selective Olefin Metathesis Catalysts. 1... 

Recent Development of Ru-Carbene Complexes for Highly Z-Selective Olefin... 

Earlier this year, the Grubbs group reported the preparation of the Ru-based catalyst with a chelating iV-heterocyclic carbene (NHC) ligand that catalyzes highly Z-selective olefin metathesis (Fig. 31) [69, 70]. This catalytic system provided similar levels of efficiency and selectivity to the W-alkylidene complexes for homocoupling reactions. The reason for the Z-selectivity is not clear at this point. Extension of the substrate scope of this catalytic system is expected. 

Fig. 31 New Ru-carbene catalyst for highly Z-selective olefin metathesis reactions...

Fig. 39 Improved njthenium catalysts for Z-selective olefin metathesis by Grubbs et al.

In 2011, Hoveyda et al. reported the total syntheses of two natural products, C18 (plasm)-16 0 (PC) (162) and KRN7000 (163), an anti-oxidant plasmalogen phospholipid and a potent immunostimulant, respectively, through catalytic Z-selective olefin cross metathesis (CM) [97]. In this study (Fig. 41), the corresponding disubstituted aUcenes were efficiently formed in good yields and excellent Z-selectivity (up to >96%) by the treatment of a molybdenum aUcylidene complex. 

A variety of pentacoordinated spirophosphoranes undergo olefination with aldehydes in the presence of t-BuOK to give a,p-unsaturated esters, amides, and nitriles with high Z selectivity (Scheme 46) [212, 217], This method has recently been extended to the Z selective olefination of ketones by modifying the pentacoordinated spirophosphoranes, which are readily prepared through the reaction of the corresponding P-H phosphoranes with a-halo carbonyl compounds in the presence of DBU [218],... 

LDA has been identified as the base of choice for the olefination of A-sulfonyl imines with semistabilized triphenylphosphonium ylides [221], A range of A-(p-toluenesulfonyl) aromatic imines undergo olefination with benzylidenetriphenylphosphoranes to give Z-stilbene derivatives with greater than 99 1 stereoselectivity (Scheme 51). The exclusive Z selective olefination reaction... 

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