Aldehydes oxygenated

After 19 hours, no reaction between the zinc chelate 2 and benzaldehyde can be detected at 20 °C. However, 10 mol % of the zinc chelate effectively catalyzes theenantioselective addition of diethylzinc to aromatic aldehydes. The predominant formation of the S-configurated products, effected by this conformationally unambiguous catalyst, can be explained by a six-mem-bered cyclic transition state assembly17. The fact that the zinc chelate formed from ligand M is an equally effective catalyst clearly demonstrates that activation of the aldehyde moiety does not occur as a consequence of hydrogen bond formation between the ammonium proton of the pyrrolidine unit and the aldehydic oxygen. 

Entry 10 was used in conjunction with dihydroxylation in the enantiospecific synthesis of polyols. Entry 11 illustrates the use of SnCl2 with a protected polypropionate. Entries 12 and 13 result in the formation of lactones, after MgBr2-catalyzed additions to heterocyclic aldehyde having ester substituents. The stereochemistry of both of these reactions is consistent with approach to a chelate involving the aldehyde oxygen and oxazoline oxygen. 

A radical cyclization of this type was used to synthesize the 4-amino-5-hydroxyhexahydroazepine group found in the PKC inhibitor balanol. The cyclization involves an a-stannyloxy radical formed by addition of the stannyl radical to the aldehyde oxygen. 

The asymmetric induction cannot be explained simply by steric interaction because the R group in the aldehyde is far too remote to interact with the tartrate ester. In addition, the alkyl group present in the tartrate ligand seems to have a relatively minor effect on the overall stereoselectivity. It has thus been proposed that stereoelectronic interaction may play an important role. A more likely explanation is that transition state A is favored over transition state B, in which an n n electronic repulsion involving the aldehyde oxygen atom and the /Mace ester group causes destabilization (Fig. 3-6). This description can help explain the stereo-outcome of this type of allylation reaction. 

A theoretical study of allylboration of aldehydes shows that (i) an initial complex may form, but if so, it is weak, and predicted reactivity trends are unchanged whether it is taken into account or not, and (ii) electron delocalization from the aldehyde oxygen to the boron p atomic orbital governs the reaction. ... 

These considerations prompted us to suggest early on that transition state A is favored as a consequence of n/n electronic repulsive interactions between the aldehydic oxygen atom and the P-face ester group that destabilizes C relative to A. c These interactions i(Rgure 25) are... 

For this mechanism to be correct, it is also necessary for the dioxaborolane to exist in conformation B with the two -COaiPr units pseudoaxial. In any other conformation of the dioxaborolane, or if other C-COaiPr bond rotational isomers are considered, the ester and aldehydic oxygen atoms are too far removed to interact. It should be noted further that reasonable transition states for C-C bond formation are not accessible if the aldehyde is symmetrically disposed with respect to the dioxaborolane system. Clockwise rotation about the B-O bond as indicated in B moves the aldehyde nonbonding lone pair away from the proximate ester carbonyl and leads to the favored transition state A. 

Originally, it was proposed that lone pair repulsions between one of the tartrate ester carbonyl oxygens and the aldehyde oxygen in transition structure 60 were responsible for the preference for transition structure 59 and the consequent enantiofacial selectivity (Scheme 5). Recent theoretical calculations. 

The liquid-phase oxidation of acrolein (AL), the reaction products, their routes of formation, reaction in the absence or presence of catalysts such as acetylacetonates (acac) and naphthenates (nap) of transition metals and the influence of reaction factors were discussed in an earlier paper (22). The coordinating state of cobalt acetylacetonate in the earlier stage of the reaction depends on the method of addition to the reaction system (25, 26). The catalyst, Co(acac)2-H20-acrolein, which was synthesized by mixing a solution of Co(acac)2 in benzene with a saturated aqueous solution, decreases the induction period of oxygen uptake and increases the rate of oxygen absorption. The acrolein of the catalyst coordinated with its cobalt through the lone pair of electrons of the aldehyde oxygen. Therefore, it is believed that the coordination of acrolein with a catalyst is necessary to initiate the oxidation reaction (10). 

Enantioselective condensation of aldehydes and enol silyl ethers is promoted by addition of chiral Lewis acids. Through coordination of aldehyde oxygen to the Lewis acids containing an Al, Eu, or Rh atom (286), the prochiral substrates are endowed with high electrophilicity and chiral environments. Although the optical yields in the early works remained poor to moderate, the use of a chiral (acyloxy)borane complex as catalyst allowed the erythro-selective condensation with high enan-tioselectivity (Scheme 119) (287). This aldol-type reaction may proceed via an extended acyclic transition state rather than a six-membered pericyclic structure (288). Not only ketone enolates but ester enolates... 

The resonance Raman spectrum of a similar complex has been reported, that of a ternary complex of LADH, NADH and 4-(7V 7V-dimethylamino)benzaldehyde (DABA) with the disappearance of the carbonyl stretching frequency of the DABA at 1664 cm-1 also indicating strongly that inner sphere complexation of the substrate occurs, the zinc withdrawing electron density from the aldehyde oxygen forming a zinc-oxygen coordinate bond.1397... 

Silyloxy-2-aldehydes can undergo hetero-Diels-Alder reaction with aldehydes to give useful heterocycles.350 A model reaction, H2C=C(OSiH3)-N=CH2 with formaldehyde, has been explored theoretically. Lewis acids such as boron trifluoride catalyse the reaction by coordinating to the aldehyde oxygen, making the aldehyde more electrophilic. Concerted and stepwise mechanisms for this process are considered. 

Aldehydes have been allylated with allyltributyltin, using supramolecular catalysis in acidic water at 60°C.196 Using j3-cyclodextrin as catalyst with all species at a 1 mmol level, high yields were obtained in a few hours. The catalyst, which can be recycled effectively, hydrogen bonds the aldehyde oxygen within the cavity. 

Studies on the various zinc-activated dehydrogenases continue apace. The reduction of tra s-4-iViV-dimethylaminocinnamaldehyde (A) by liver alcohol dehydrogenase (LADH) is reported to involve the zinc at the active site of the enzyme acting as a Lewis acid and co-ordinating the substrate via the aldehyde oxygen.235 The kinetics of the reaction show that (A) 4- LADH -f NADH form a stable intermediate at pH 9, the overall reaction sequence being ... 

The stereochemical outcome was rationalized by a Zimmerman-Traxler type transition state 45.64 Assuming the titanium enolate of 42 has a Z-geometry and forms a 7-membered metallacycle with a chairlike conformation, a model can be proposed where a second titanium metal coordinates to the indanol and aldehyde oxygens in a 6-membered chairlike conformation. The involvement of two titanium centers was supported by the fact that aldehydes that were not precomplexed with titanium tetrachloride did not react (Scheme 24.7).63 Ghosh and co-workers further hypothesized that a chelating substituent on the aldehyde would alter the transition state 46 and consequently the stereochemical outcome of the condensation, leading to. vyn-aldol products 47.64 Indeed, reaction of the titanium enolate of 42 with bidentate oxyaldehydes proceeded with excellent. s v -diastereo-selectivity (Scheme 24.8).65... 

The best result using aldehyde/oxygen was reported recently by Qi et al. [53] using novel Ru(HL)(L)C12 (HL is N-2 chlorophenyl-2-pyridine-carboxamide) complexes and isobutyraldehyde/oxygen for the epoxidation of cycbc alkenes. The turnover frequencies (TOFs) in this system were as high as 350 h 1 for cyclohexene, with a selectivity towards the epoxide of 87% (see Eq. 12). 

Roush et al. discovered that the tartrate ester-modified allylboronates, such as diisopropyl tartrate allylboronate (.S, .S )-41, react with achiral aldehydes to give the homoallylic alcohols 42 in good yields and high levels of enantioselectivity of up to 87% ee when the reaction is carried out in toluene in the presence of 4-A molecular sieves20 (Scheme 3.1q). To rationalize the asymmetric induction realized by 41, two six-membered transition states were compared (Scheme 3.1r). It was reasoned that transition state A was favored over transition state B due mainly to the nonbonded electronic repulsive interactions of the lone-pair electrons of the aldehyde oxygen and the carbonyl oxygen of the tartrate ester. 

For the reaction in an organic solvent (THF), they obtained a single TS 75 (Figure 6.27). In this TS, the new C-C bond is formed in conjunction with the proton transfer from the enol to the aldehyde oxygen (Reaction 6.29). The activation energy for this reaction is 18.6 kcal mol ... 

The four steps, after participation of the aldehyde oxygen, are (1) nucleophilic reaction of water with the most electrophilic carbon (2) loss of a proton (3) protonation of the nitrogen and (4) loss of diethylamine. Writing the steps in this order avoids formation of more than one positive charge in any intermediate. 

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