E/Z selectivity

In 1995, palladium-catalyzed reduction of vinylaziridines with formic acid was reported [42]. As shown in Scheme 2.26, 1,2-reduction products 95 and 1,4-products 96 were obtained in ratios depending on the reaction conditions, such as the additive, solvent, and catalyst employed. Both the E/Z selectivity of 95 and the... 

In our work with aminolysis of vinylepoxides (see Section 9.2.1.1), the substrates were routinely synthesized by SAE followed by Swern/Wittig reactions (Table 9.3, Entries 1-4) [48, 49]. This procedure is well suited for terminal olefins, but dis-ubstituted olefins can seldom be obtained with useful (E Z) selectivities. Nakata recently synthesized some advanced intermediates towards natural products in this manner (Entries 5, 6) [50, 51]. 

The E/Z selectivity problem is restricted to cross metathesis and RCM leading to macrocycles (macro-RCM). Both aspects have recently been covered in reviews by Blechert et al. [8d] and by Prunet [44]. E/Z selectivity can be influenced by reaction temperature, solvent or substitution pattern of the substrate. Here, we will only discuss the influence of the precatalyst. 

Bent ansa-metallocenes of early transition metals (especially Ti, Zr, Hf) have attracted considerable interest due to their catalytic activity in the polymerization of a-olefins. Ruthenium-catalyzed olefin metathesis has been used to connect two Cp substituents coordinated to the same metal [120c, 121a] by RCM or to connect two bent metallocenes by cross metathesis [121b]. A remarkable influence of the catalyst on E/Z selectivity was described for the latter case while first-generation catalyst 9 yields a 1 1 mixture of E- and Z-dimer 127, -127 is the only product formed with 56d (Eq. 19). 

E.Z-Selectivity in the insertion by unsymmetrical carbenoid 24, is specifically indicative of the transition state of the stepwise mechanism. Based on the evidence that carbenoid 24, which is generated from 42 or 43 (E Z = 84 16), exists nearly exclusively in the -configuration under the equilibrium even at —95°C,29 the observed stereoselectivity for E-isomers in the insertion products verifies that hydride abstraction takes place via an Sn2-like transition state 52 with inversion of configuration at the carbenoid carbon, followed by the recombination of menthone 40 and carbanion 53 (Scheme 19). 

Dependence on Metallocene Symmetry of E-Z Selectivity for 2-Butene Copolymerizations. We have seen in the Section 3.1.3 that opposite enantiofaces are favored for primary and secondary propene insertion on C2-symmetric metallocenes, whereas the same enantioface is favored for primary and secondary insertion on Cv-symmetric metallocenes. In this framework, if the same steric interactions which rule the enantioselectivity of primary and secondary propene insertions hold for 2-butene, the insertion of... 

In summary, the prediction that (E)-(Z) selectivity in the ethene/intemal olefins copolymerization with group 4 metallocenes can be achieved by using ligands of suitable symmetry has been proved. In particular, it has been shown that C2- and Os-symmetric metallocenes are able to copolymerize ethene with (Z)- and ( >butene, respectively. 

As for olefins different from propene, molecular modeling studies have also been able to rationalize the dependence on metallocene symmetry of E-Z selectivity for 2-butene copolymerization as well as the stereoselectivity of the cyclization step, which determines the cis or trans configuration of the rings, for cyclopolymerization of nonconjugated dienes. 

Tsuji and co-workers carbonylated a-carbonate-substituted allenes 113 with carbon monoxide and methanol, which provided 114 in excellent yields (Scheme 14.25) [54], They found that allenylic carbonates are more reactive than simple allylic carbonates and that the reaction proceeded rapidly even at ambient temperature under atmospheric pressure of carbon monoxide. Unfortunately, the poor E/Z selectivity diminishes the synthetic value of this very efficient carbonylation reaction. 

A high-level quantum chemical exploration of the Horner-Wandsworth-Emmons reaction has indicated that ring closure of the P—O bond (which favors formation of -product) is rate determining in the gas phase and that the C—C bond-forming addition step is rate determining in most solvated systems several effects that could account for the E/Z selectivities observed have been identified. 

As described above in Eq. 43, simple allylboronates can be transformed into more elaborated ones using olefin cross-metathesis. " Treatment of pinacol allylboronate 31 with a variety of olefin partners in the presence of Grubbs second-generation catalyst 142 smoothly leads to formation of 3-substituted allylboronates 143 as cross-metathesis products (Eq. 104). Unfortunately, these new allylic boronates are formed as mixtures of geometrical isomers with modest E/Z selectivity. They are not isolated but rather are treated directly with benzaldehyde to give the corresponding homoallylic alcohol products in good yields (Table A). 

Stabilized ylides react with aldehydes in water to give Wittig products, sometimes with remarkable acceleration.260 For example, pentafluorobenzaldehyde reacts with ester-stabilized ylide, Ph3P=CHC02Me, at 20 °C in 5 min in 86% yield, with 99 1 E Z-selectivity. Water s ability to stabilize the polar transition state of the reaction, and its participation in the reaction (as determined by deuterium exchange), are discussed. 

Chiral CHdo-alcohols (Fig. 35D (R = Et), F and G) as proton source mediate the enantioselective protonation of Sm-enolates according to Scheme 31 [255]. The optimal molar ratio of DHPEX (Fig. 35G) and HMPA were about 0.7 and 0.6, respectively. Steric factors dominate the enantioselectivity of this reaction sequence when unsymmetrical dialkylketenes are used. High enantiomeric excesses were achieved when the difference between the bulkiness of the alkyl groups for a given substrate is large. The relationship between the enantioselectivity of the protonation and the E/Z selectivity of Sm-enolate formation which is dependent on type of alkyl substitiution was examined. 

If the R-group in the alkyne is a strongly electron-withdrawing moiety such as a carbonyl function, regioselectivity may be reversed, leading to the problem of E/Z-selectivity (Scheme 2). Irrespective of the type of alkyne, the one-step atom-economical process would need to be catalyzed because a simple thermal process does not provide the products. 

A key challenge in M-RCM, especially for the construction of unsaturated targets in which the olefin moiety is installed during the metathesis reaction, is the control of the E/Z selectivity. This applies not only to macrocycles but also to medium-size... 

Scheme 2.13 E/Z selectivity by choice of the catalyst synthesis of herbarumin I and II.

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