Transition state assembly

Evans and co-workers investigated the effect of a number of -symmetric bis(oxazoline) ligands on the copper(II)-catalysed Diels-Alder reaction of an N-acyloxazolidinone with cyclopentadiene. Enantiomeric excesses of up to 99% have been reported (Scheme 3.4). Evans et al." suggested transition state assembly 3.7, with a square planar coordination environment around the central copper ion. In this scheme the dienophile should be coordinated predominantly in an cisoid fashion in... 

Fig. 3.5 Bimetallic transition state assembly for directed cy-clopropanation...

A transition state assembly as depicted in Scheme 1.23 was proposed in order to interpret the observed selectivity. Electronic effects are thought to be operative, as the methyl and bromo substituents in transition state 83 are sterically similar. 

The transition state assembly 55 (Figure 3.8), that rationalizes the stereochemistry of the cycloadduct, is consistent with the structure of the chiral catalyst determined by an X-ray diffraction study. Interestingly it has been shown [58] that in the cycloadditions of maleimides 56 with 2-methoxy-l,3-butadiene, the enantioselection depends on the bulkiness of Ar and Ari groups of catalyst 54 and dienophile 56, respectively (Scheme 3.13). The importance of the bulky Ari... 

Finally, Mikami and Motoyama have used a p-hydroxy sulfonamide ligand to catalyse the enantioselective B-catalysed Diels-Alder reaction of glyoxylate with Danishefsky s dienes." " A favourable transition-state assembly for a one-directional diene-approach from the site proximal to the sulfonylamino moiety was proposed to explain the observed high enantio- and c (e fi o)-diastereos-electivity (Scheme 5.28). 

Saito and coworkers have used C2-symmetrical alkenes derived from a variety of tartaric acid derivatives, for controller in discriminating 71 faces of dipolarophile in nitrone cycloaddition. Excellent endolexo and diastereofacial selectivity (de) are obtained. Endo transition state assembly shown in Eq. 8.50 could be responsible for the formation of preferred distereoisom-... 

The observed absolute stereopreference can be understood in terms of two proposed transition-state assemblies, 27 and 28 (Figure 12.2). The direction of the H—O bond of (R)-26 might be fixed in the naphthoxy plane by bidentate chelation... 

Figure 12.3. Two transition-state assemblies 33 and 34 in the proton-induced cyclization of ( )-29.

Under these conditions, the Z-enolate is formed and the aldol adducts have syn stereochemistry. The addition can proceed through a cyclic transition state assembled around titanium. 

An alternate mechanism invoking an ion-pair transition-state assembly has been proposed to account for the enantioselectivity of the asymmetric epoxidation process [137]. In this proposal, two additional alcohol species are required in the transition-state complex. This... 

Diels-Alder reaction of 2-bromoacrolein and cyclopentadiene using 10 mol% of titanium catalyst 74 gave the synthetically versatile (R)-bromoaldehyde adduct 75 in 94% yield, 67 1 exo. endo diastereoselectivity, and 93% ee. The absolute stereochemical outcome of the reaction is consistent with the proposed transition state assembly 76 in which the dienophile coordinates at the axial site of the metal, proximal to the indane moiety through Ji-attractive interactions. In this complex, the 7t-basic indole and the Ji-acidic dienophile can assume a parallel orientation facilitated by the octahedral geometry of the transition metal. The aldehyde would then react through a preferential s-cis conformation (Scheme 17.27).54... 

The boron-substituent-dependent enantioselectivity of CAB-catalyzed Diels-Alder reactions has been studied as a first step toward obtaining mechanistic information on the sp -sp conformational preferences in a, d-enals, where the possibility of s-cis or s-trans conformers exists in the transition-state assembly of Diels-Alder reaction catalyzed by Lewis acid [12]. a-Substituted a,P-ena s (e.g. methacrolein) favors an s-trans conformation in the transition-state assembly irrespective of the steric features of the boron substituent. On the other hand, the sp -sp conformational preference of a-unsubstituted a,/3-enals (acrolein and crotonaldehyde) can be reversed by altering the structure of the boron substituent an s-trans conformation is preferred when the substituent on the boron is small (H, C=CBu), whereas an s-cis conformation is preferred when the substituent is bulky (o-PhOC(jH4). 

The absolute stereo-preference in the Diels-Alder reaction can be easily understood in terms of the most favorable transition-state assembly 5, in which an attractive donor-acceptor interaction favors coordination of the dienophile at the face of boron which is cis to the 2-hydroxyphenyl substituent. At this time, the conformation of a,y3-enal has a strong s-trans preference. We believe that the coordination of a proton of the 2-hydroxyphenyl group with an oxygen of the adjacent B-O bond in complex 5 plays an important role in asymmetric induction this hydrogen-bonding interaction via a Brpnsted acid would cause the Lewis acidity of boron and the jr-basicity of the phenoxy moiety to increase, and the transition-state assembly 5 would be stabilized. The jr-basic phenoxy moiety and the jr-acidic dienophile could then assume a parallel orientation at the ideal separation (3 A) for donor-acceptor interaction. In this conformation, the hydroxyphenyl group blocks the si face of the dienophile, leaving the re face open to approach by diene. 

The fl ri-preference of the BF3-propynal complex in the transition-state assembly, as suggested by our calculations, might be adapted to complexes with bulky chiral Lewis acids such as 2,4 and 6. 

To identify the stereochemical course of the protonation of the vinyl carbon, cis and trans silyl enol ethers derived from menthone were isomerized by use of a deuter-ated achiral proton source. Surprisingly, only the identical syn isomer was obtained from both the silyl enol ethers. Thus reaction of the cis isomer occurs via an anti Se mechanism whereas reaction of the trans isomer occurs via a syn Se mechanism. Interestingly, this cis silyl enol ether was isomerized more rapidly than the trans isomer. In the cis silyl enol ether, deuterium was located at a psewdo-axial position in the isomerized product. Therefore, the anti-S pathway can be explained by the product developing control via the product-like transition state assembly. The syn-S pathway for the trans silyl enol ether can be explained by substrate control via the favored intermediate. The relative contributions of the two pathways depend on the relationship between the free energies of their transition state assemblies (Sch. 8). 

One interesting possibility emerges from the likelihood that an n-71 interaction between an oxygen lone pair of LBA and jr electrons of the terminal carbon-carbon double bond of the substrates stabilizes the transition state of the cyclization or the initial protonation step. The transition-state assembly proposed on the basis of this assumption and the steric repulsion would clearly lead to predominant approach of (i )-LBA to the si face of the terminal isoprenyl group (Fig. 4). 

The slow nucleophilic addition of dialkylzinc reagents to aldehydes can be accelerated by chiral amino alcohols, producing secondary alcohols of high enantiomeric purity. The catalysis and stereochemistry can be interpreted satisfactorily in terms of a six-membered cyclic transition state assembly [46,47], In the absence of amino alcohol, dialkylzincs and benzaldehyde have weak donor-acceptor-type interactions. When amino alcohol and dialkylzinc are mixed, the zinc atom acts as a Lewis acid and activates the carbonyl of the aldehyde. Zinc in this amino alcohol-zinc complex is regarded as a kind of chirally modified Lewis acid. Various kinds of polymer-supported chiral amino alcohol have recently been prepared and used as ligands in dialkylzinc alkylation of aldehydes. 

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