Aldehydes conformational stability

According to this concept, the aldol condensation normally occurs through a chairlike transition state. It is further assumed that the stmcture of this transition state is sufficiently similar to that of chair cyclohexane to allow the conformational concepts developed for cyclohexane derivatives to be applied. Thus, in the example above, the reacting aldehyde is shown with R rather than H in the equatorial-like position. The differences in stability of the various transition states, and therefore the product ratios, are governed by the steric interactions between substituents. 

Additionally, it was found that the energy difference between the two transition states (3 and 4) is determined mainly by the difference in the conformational energy of the a-chloro aldehyde in the two transition states i.e., the energetic preference of transition state 3 over 4 is due to a more favorable conformation of the aldehyde rather than a more favorable interaction with the attacking nucleophile. In fact, interaction between lithium hydride and 2-chloropropanal stabilizes transition state 4, which yields the minor diastereomer. 

A degree of stereoselective control of the course of a reaction, which is absent or different from that prevalent when the reaction is conducted in the absence of quaternary ammonium salts, may be achieved under standard phase-transfer catalysed reaction conditions. The reactions, which are influenced most by the phase-transfer catalyst, are those involving anionic intermediates whose preferred conformations or configurations can be controlled by the cationic species across the interface of the two-phase system. For example, in the base-catalysed Darzens condensation of aromatic aldehydes with a-chloroacetonitriles to produce oxiranes (Section 6.3), the intermediate anion may adopt either of the two conformations, (la) or (lb) which are stabilized by interaction across the interface by the cations (Scheme 12.1) [1-4]. 

Rather, the conformational bias in our substrates is apparently dependent on a very particular relationship between the formyl moiety and unsaturated in the pendant side chain. As a result of our studies, we speculate that the presence of unsaturation at C4-C5 in the aldehyde moiety provides a subtle stabilizing nonbonded interaction between the unsaturation in the aldehyde and the carbonyl of the enolate (Table 2.1,... 

The cavitands are essentially synthesized from their resorc[4]arene precursors which are readily obtained by resorcinol condensation with aldehydes. The main feature comes from the different configurations that are expected for this tetrameric species and the relative thermodynamical stability of each isomer, which has been widely investigated by several authors. In addition, the conformational mobility of the resorc[4]arene molecules will depend on substitution at the upper and lower rims [28, 36, 40, 41]. The first attempt to synthesize a phosphorus bridged cavitand was to treat resorc[4]arene la (1, R=CH3) with phenylphosphonic dichloride or phenylphosphonothioic dichloride. Only inseparable isomer mixtures were obtained and isolation of the desired cavitands was not possible [42]. The first isolated phosphorylated resorcinol-based cavitand was described in 1992 by Markovsky et al., who prepared compound D from la and four equivalents of o-phenylenechlorophos-phate in the presence of triethylamine [43, 44]. For this compound, a tautomeric temperature and solvent dependent equilibrium exists between the spirophosphorane structure and the cyclic phosphate form (Scheme 4). 

One further point is worthy of brief mention. While we have focused on lone pair/lone pair repulsive interactions that destabilize transition state C, it is conceivable that A is actually stabilized relative to C by a favorable charge-charge interaction between the ester carbonyl (5 ) and the aldehydic carbonyl carbon (5+) owing to the proximity of these groups in A. While it is not yet possible to resolve the relative contributions of these distinct stereoelectronic effects, it is clear that our mechanistic proposal e)mlains the experimental results only if the dioxaborolane and the C-COaiPr bonds exist in the conformations indicated in B. Any conformational infidelity at either site would be expected to lead to diminished enantioselectivity. 

The energetics relative to the conformational problem of pyridine-2-carboxaldehyde thus appear qualitatively similar to that of furan-2-carbox-aldehyde the less polar conformer is more stable as an isolated molecule and polar media are likely to reverse the relative stability. Nevertheless, while the energy difference between cis and trans forms of 2-formyl derivative of furan becomes nearly zero in solvents of relatively low polarity (72T3015), the same seems to occur for pyridine derivative in more polar solvents. 

In addition to aldehydes and ketones, a variety of other functional groups can be used as electrophiles in Reformatsky-type reactions.1-3 Among them, nitriles play a prominent role since they lead to p-oxoesters after hydrolytic work-up (the primary enamines initially formed can only be isolated when stabilized by extended conjugation or by conformational means, cf. Table 14.1, entry 4). 

T(2-Alkylcycloalk-l-enyl)methyl carbamates of type 56 are useful 1,2-dianion synthons that can be combined with two aldehydes in adjacent positions to provide a versatile synthesis of [fjannulated tetrahydrofurans (Scheme 81). At first, a carbanion of carbamate 56, which exhibits considerable configurational stability, is generated by (—)-sparteine-mediated deprotonation this is then converted to an optically active homoaldol product 57 with up to %% ee. An (it)-oxonium ion, which is subsequently formed under the influence of BF3, undergoes an intramolecular Mukaiyama-type addition of the enolic moiety onto the carbonyl group of a second aldehyde in the least-hindered conformation. Finally, the carhamoyl group is extmded, and after aqueous workup, diastereomerically pure tetrahydrofurans can be isolated <2005ASC1621>. 

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