Chelated intermediates

The mechanism of organolithium addition to naphthyl oxazolines is believed to occur via initial complexation of the alkyllithium reagent to the oxazoline nitrogen atom and the methyl ether to form chelated intermediate 17. Addition of the alkyl group to the arena 7t-system affords azaenolate 18, which undergoes reaction with an electrophile on the opposite face of the alkyl group to provide the observed product 4. The chelating methyl... 

Substantially high diastereoselectivity was accomplished by the conjugate addition of Grignard reagents to the amide 1 derived from 1-ephedrine32. The reagent attacked from the Re-face of the double bond, as shown in 2, via a chelated intermediate. Low asymmetric induction was observed when butyllithium was used instead of butylmagnesium bromide. 

On the other hand, a 10 1 diastereofacial preference in favor of 3b was realized by way of a chelated intermediate starting from (Z)-5-benzyloxy-3-hexen-2-one. 

While a different explanation for the diastereoselection in these protonation reactions has been proposed, the stereochemical sense of protonation can be rationalized as arising from protonation of the chelated intermediate from the least hindered diastereotopic face of the nitronate anion (i.e. anti to the /i-methyl group)20-21. 

The stereochemical outcome could be rationalized by attack on the chelated intermediate from the diastereoface of the enolate that is anti to R1. 

Zinc bromide promoted addition of a functionalized benzyl Grignard reagent to the a,/ -unsat-urated y-lactone, 3-(4-methylphenylsulfinyl)-2(5//)-furanone, via a zinc-chelated intermediate, gave, after several synthetic steps, (-)-podorhizon with 95% ee18. 

Enantiomerically pure 3-tolyl-2-sulfinyl-2-cyclopentenone 37 undergoes smooth, mild and diastereoselective conjugate hydride addition with lithium tri(sec-butyl)borohydride to afford ultimately 3-tolylcyclopentanone 38 in 93% enantiomeric purity (equation 35)78. The absolute stereochemistry of product 38 is consistent with a chelated intermediate directing hydride addition from that diastereoface containing the sulfoxide lone pair. 

McLafferty rearrangement 133, 163 Meisenheimer complexes 699, 702 Metal-chelated intermediates 838 Metal-halogen exchange 781, 784 Methionine, oxidation of 852-855 Methionine sulphone 853 Methionine sulphoxide 851-869 reduction of 1063 residues of... 

In contrast to a, -ethylenic ketones or even a, -ethylenic sulfones, a, ) -ethylenic sulfoxides generally are not sufficiently electrophilic to undergo successful nucleophilic j8-addition . a-Carbonyl-a, j8-ethylenic sulfoxides, however, are potent, doubly activated alkenes which undergo rapid and complete -addition of various types of nucleophiles even at — 78 °C. A brief account summarizing this area is available . The stereochemical outcome of such asymmetric conjugate additions to enantiomerically pure 2-sulfmyl 2-cycloalkenones and 2-sulfinyl-2-alkenolides has been rationalized in terms of a metal-chelated intermediate in which a metal ion locks the -carbonyl sulfoxide into a rigid conformation (36 cf. 33). In this fixed conformation, one diastereoface of the cyclic n... 

Another reagent that has found use in pinacolic coupling is prepared from VC13 and zinc dust.264 This reagent is selective for aldehydes that can form chelated intermediates, such as (3-formylamides, a-amidoaldehydes, a-phosphinoylaldehydes,265 and 8-ketoaldehydes.266 The vanadium reagent can be used for both homodimerization and heterodimerization. In the latter case, the reactive aldehyde is added to an excess of the second aldehyde. Under these conditions, the ketyl intermediate formed from the chelated aldehyde reacts with the second aldehyde. 

Several important classes of polar monomers have so far eluded copolymerization by the Pd(II) system. Vinyl chloride insertion, for example, leads to catalyst deactivation following P-halide elimination to form inert chloride species such as 1.32, as shown by Jordan [90], Similarly, attempted vinyl acetate copolymerization results in deactivation by an analogous acetate elimination process, although the ester chelate intermediate that forms after insertion also effectively shuts down the reaction [90], Therefore, -elimination of polar groups represents a significant and unresolved problem for late transition metal polymerization systems unless access of the metal to it is restricted. 

The diastereofacial selectivity is explained by the proposed chelated intermediate 151. Internal delivery of the nucleophile takes place from the less hindered side. Removal of the chiral directing moiety with a catalytic amount of palladium hydroxide on carbon in absolute ethanol then furnishes the final product. This process yields the amino ester in 83-100% yield without observable racemization. 

Figure 4.7. Acylated Oppolzer s sultam 66 and proposed Zr-chelate intermediate 67.

Aldehydes react with dimethyl 2-phenylselenofumarate (70) at -70 °C in diethyl ether in the presence of MeLi to give good yields of highly substituted 4-phenylselenobutano-y-lactones (71) and (72). High diastereoselectivity [for benzaldehyde, (71) (72)-89 11] was rationalized by assuming the formation of a chelated intermediate between MeLi and (70), with approach of the aldehyde from the favoured si-fact (Scheme 5). " ... 

Kinetic studies on the oxidation of glutamate by manganese(III) in aqueous sulfuric acid, acetic acid, and pyrophosphate suggest different mechanisms for each case. In all cases there is evidence for the involvement of free radicals and in the case of acetic acid and pyrophosphate media a chelated intermediate is postulated. Simultaneous Mn(III)/Mn(IV)-mediated reaction is observed in the oxidation of formaldehyde by... 

Only with less efficient catalysts and at low temperature, have p-chelate intermediates been intercepted by P H HP NMR spectroscopy in the course of copolymerisations in MeOH-d4 [5g]. The unambiguous detection of p-chelates has been observed in a reaction catalysed by the l,r-bis(diphenylphosphino)ferro-cene complex [Pd(H20)2(dppf)](0Ts)2 (3) at room temperature (Scheme 7.7) [5g]. As shown in the sequence of P H NMR spectra reported in Figure 7.8, the P-chelate intermediates 4- disappeared already at 50 °C. A parallel model study confirmed the formation and the structure of the dppf P-chelates and also provided information of more elusive intermediates (see Section 7.2.1.8) [19]. 

Carbanions of enantiomerically pure sulfoxides have been investigated as precursors for asymmetric synthesis. However, they react with carbonyl compounds with modest selectivity. This selectivity is increased by the incorporation of an ester group adjacent to the carbanionic center. The observed stereochemistry in this reaction is consistent with chelated intermediates, where magnesium chelate is particularly efficient, as illustrated in equation 91 " . ... 

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