Aldehydes chelated

Aldehyde Steric Aldehyde Chelate Aldehyde Polar... 

The substitution of the remaining acetylacetonate rings provided additional evidence of the assigned aldehyde chelate structures and opened the way for the preparation of a number of unsymmetrically substituted chelate rings. 

Mikami has also reported a related ene-like process involving glyoxylates and ketone-derived enolsilanes 42 (Eq. 8B2.11) [17]. The enol ether adducts 43 yield the corresponding P-hydroxy ketone upon treatment with mild acid. On the basis of an analysis of the stereo- and regiochemical outcome of the addition reaction Mikami has invoked a monodentate complex between aldehyde and metal, in contrast to the typical transition-state structures involving glyoxylates that are suggested to involve metal/aldehyde chelates. 

In the stereochemical model of the catalyst-aldehyde chelate complex, the square pyramidal complex 28 [39], the re aldehyde enantioface is shielded by the ligand phenyl group exposing the si enantioface to nucleophilic attack (Fig. 1-9). Since enantioselective formation of (5)-/(-hydroxy esters is observed (si face attack), the absolute stereochemistry of the products is consistent with the proposed coordination model. 

Reaction of the /y-benzyloxy-o-methyl chiral aldehyde 97a with (/ )-crolylsi-lanes 217 (R = H, Et) under catalysis by TiC affords the ann,antt-dipropionate adduct 362 (Eq. (11.29)). The diastereoselectivity in this reaction is best explained by anti S e addition of the chiral crotylsilane to the least hindered face of the fi-alkoxy aldehyde chelate, as shown in the synclinal transition state 363. Finally, the anri.syn-dipropionate 364 may be obtained as the major adduct when aldehyde 97a is treated under the same conditions with the enantiomeric crotylsilane reagents (5)-217 (Eq. (11.30), R=Me, Et). This adduct should arise from the antiperiplanar transition state 365, where the anti S e facial selectivity of the crotylsilane reagent and the facial bias of the chiral aldehyde are maintained. In these cases, the factors that dictate the utilization of the synclinal vs the antiperiplanar transition states are (1) the requirement that a small substituent (H) occupy the position over the chelate ring, (2) that C-C bond formation occurs anti to the sterically demanding a-methyl group of the aldehyde and (3) the requirement for an anti Se mechanism, which dictates the stereochemistry of C(5) of the adducts 362 and 364. 

The utility of BF3-OEt2, a monodentate Lewis acid, for acyclic stereocontrol in the Mukaiyama aldol reaction has been demonstrated by Evans et al. (Scheme 10.3) [27, 28]. The BF3-OEt2-mediated reaction of silyl enol ethers (SEE, ketone silyl enolates) with a-unsubstituted, /falkoxy aldehydes affords good 1,3-anti induction in the absence of internal aldehyde chelation. The 1,3-asymmetric induction can be reasonably explained by consideration of energetically favorable conformation 5 minimizing internal electrostatic and steric repulsion between the aldehyde carbonyl moiety and the /i-substituents. In the reaction with anti-substituted a-methyl-/ -alkoxy aldehydes, the additional stereocontrol (Felkin control) imparted by the a-substituent achieves uniformly high levels of 1,3-anti-diastereofacial selectivity. 

Meyers has demonstrated that chiral oxazolines derived from valine or rert-leucine are also effective auxiliaries for asymmetric additions to naphthalene. These chiral oxazolines (39 and 40) are more readily available than the methoxymethyl substituted compounds (3) described above but provide comparable yields and stereoselectivities in the tandem alkylation reactions. For example, addition of -butyllithium to naphthyl oxazoline 39 followed by treatment of the resulting anion with iodomethane afforded 41 in 99% yield as a 99 1 mixture of diastereomers. The identical transformation of valine derived substrate 40 led to a 97% yield of 42 with 94% de. As described above, sequential treatment of the oxazoline products 41 and 42 with MeOTf, NaBKi and aqueous oxalic acid afforded aldehydes 43 in > 98% ee and 90% ee, respectively. These experiments demonstrate that a chelating (methoxymethyl) group is not necessary for reactions to proceed with high asymmetric induction. 

The carbanions derived from acylthiophenes have been condensed with aldehydes,and, through the Claisen condensation with esters, thienylsubstituted -diketones have been obtained. 2-Thenoyl trifluoroacetone, first prepared by Reid and Calvin through the Claisen condensation of 2-acetylthiophene with ethyl trifluoracetate, has become an extremely useful chelating agent for the extraction of numerous elements from strongly acidic solutions, The tautomeric form which dominates in aqueous solution is the ketone hy-drate. Other thiophenes have also proved useful for analytical purposes. ... 

Although it may not be obvious, putative intermediate 12 could conceivably be fashioned in one step from lactol 13. Of course, 13 can be regarded as a latent aldehyde that should be amenable to an a-chelation-controlled carbonyl addition reaction21 with ethyl-magnesium bromide. This event could secure the formation of the indicated stereocenter in intermediate 12. It seems reasonable to suppose that the sequential action of aqueous acid and 1,1-... 

The addition of vinylmagnesium bromide to methyl (S)-3-benzyloxy-4-oxobutanoate (5) in tetrahydrofuran proceeded with a slight preference for the nonchelation-controlled reaction product (40 60)5°. A reversal of the diastereoselectivity (80 20) could be observed when the Grignard reagent, as a solution in tetrahydrofuran, was added to a dichloromethane solution of the aldehyde which had been precomplexed with one equivalent of magnesium bromide. The almost exclusive formation of the chelation-controlled reaction product 6 was achieved when tetrahydrofuran was completely substituted by dichloromethane the presence of tetrahydrofuran interferes with the formation of the chelate complex, which is a prerequisite for high chelation-controlled diastereoselection. 

Addition of alkynes to a-alkoxy aldehydes is most favorably performed with the corresponding zinc reagents (Table 12)46. As with Grignard reagents, the chelation-controlled addition of zinc alkynes proceeds with higher diastereoselectivity when diethyl ether rather than tetrahydrofuran is used as reaction solvent. 

The lower diastereoselectivity found with aldehyde 15 (R = CH3) can be explained by the steric influence of the two methyl substituents in close vicinity to the stereogenic center, which probably diminishes the ability of the ether oxygen to coordinate. In contrast, a significant difference in the diastereoselectivity was found in the additions of phenyllithium and phenylmagnesium bromide to isopropylidene glyceraldehyde (17)58 (see also Section 1.3.1.3.6.). Presumably the diastereo-sclcctivity of the phenyllithium addition is determined by the ratio of chelation-controlled to nonchelation-controlled attack of the nucleophile, whereas in the case of phenylmagnesium bromide additional chelation with the / -ether oxygen may occur. Formation of the -chelate 19 stabilizes the Felkin-Anh transition state and therefore increases the proportion of the anZz -diastereomeric addition product. 

A synthetically useful diastereoselectivity (90% dc) was observed with the addition of methyl-magnesium bromide to a-epoxy aldehyde 25 in the presence of titanium(IV) chloride60. After treatment of the crude product with sodium hydride, the yy -epoxy alcohol 26 was obtained in 40% yield. The yyn-product corresponds to a chelation-controlled attack of 25 by the nucleophile. Isolation of compound 28, however, reveals that the addition reaction proceeds via a regioselective ring-opening of the epoxide, which affords the titanium-complexed chloro-hydrin 27. Chelation-controlled attack of 27 by the nucleophile leads to the -syn-diastereomer 28, which is converted to the epoxy alcohol 26 by treatment with sodium hydride. 

The nucleophilic addition of Grignard reagents to a-epoxy ketones 44 proceeds with remarkably high diastereoselectivity70. The chelation-controlled reaction products are obtained in ratios >99 1 when tetrahydrofuran or tetrahydrofuran/hexamethylphosphoric triamide is used as reaction solvent. The increased diastereoselectivity in the presence of hexamethylphos-phoric triamide is unusual as it is known from addition reactions to a-alkoxy aldehydes that co-solvents with chelating ability compete with the substrate for the nucleophile counterion, thus reducing the proportion of the chelation-controlled reaction product (vide infra). 

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