Conformation of aldehydes

Figure 7.6 Calculated conformations of aldehydes 28, 29, 32, and 33. Dot lines on 29 and 33 indicate hydrogen bondings and arrows show the approach trajectory of nucleophile.

Figure 2. Transoid (16a) and cisoid (16b) rotomers of the preferred conformer of aldehyde 16. Nucleophilic attack could be predicted to occur upon the less sterically encumbered a-face of 16a to provide the C-1 S diastereomer 30.

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. 

On the basis of this analysis, it may be anticipated that the extent of aldehyde diastereofa-cial selectivity will depend on the difference in size of the R3 aldehyde substituent relative to that of the methyl group. The examples summarized in Table 2 are generally supportive of this thesis, particularly the reactions of (F)-2-butenylboronntc. The data cited for reactions of 3-methoxymethoxy-2-methylbutanal with (Z)-2-butenylboronate and 2-propenylboronate, however, also show that diastereoselectivity depends on the stereochemistry at C-3 of the chiral aldehydes. These data imply that simple diastereoselectivity depends not simply on reduced mass considerations, but rather on the stereochemistry and conformation of the R3 substituent in the family of potentially competing transition states21,60. The dependence of aldehyde diastcrcofacial selectivity on the stereochemistry of remote positions of chiral aldehydes has also been documented for reactions involving the ( )-2-butenylchromium reagent62. 

Entry 6 involves a titanium enolate of an ethyl ketone. The aldehyde has no nearby stereocenters. Systems with this substitution pattern have been shown to lead to a 2,2 syn relationship between the methyl groups flanking the ketone, and in this case, the (3-siloxy substituent has little effect on the stereoselectivity. The configuration (Z) and conformation of the enolate determines the 2,3-vyn stereochemistry.113... 

The reacting aldehyde displaces the oxazolidinone oxygen at the tetravalent boron in the reactive TS. The conformation of the addition TS for boron enolates is believed to have the oxazolidinone ring oriented with opposed dipoles of the ring and the aldehyde carbonyl groups. 

Synclinal and antiperiplanar conformations of the TS are possible. The two TSs are believed to be close in energy and either may be involved in individual systems. An electronic tt interaction between the stannane HOMO and the carbonyl LUMO, as well as polar effects appear to favor the synclinal TS and can overcome the unfavorable steric effects.161bi 162 Generally the synclinal TS seems to be preferred for intramolecular reactions. The steric effects that favor the antiperiplanar TS are not present in intramolecular reactions, since the aldehyde and the stannane substituents are then part of the intramolecular linkage. 

The stereospecific preparation of aldehyde ester 462, already comprising five of the six stereo centers of the molecule and, furthermore, the stereoselective construction of the epialloyohimbane skeleton with Ec2 conformation are regarded the remarkable features of Woodward s approach. 

The allenylsilane ene reaction is also well suited for the synthesis of cyclohexane rings. Jin and Weinreb have described the process of Eq. 13.55 in a synthesis of 5,11-methanomorphanthridine, an Amaryllidaceae alkaloid [64], Conversion of aldehyde 163 to imine 164 with piperonylamine took place in situ. Heating the solution of imine at reflux in mesitylene for 2 h led to cyclization through the conformer shown. The yield of 165 from aldehyde 163 was 66%. 

FIGURE 5. Important conformations of Lewis acid complexed aldehydes... 

The results obtained for ligands 48 and 50, which contain only one fixed stereocentre, are interesting and very informative about the system. Ligand 48-(R,—), in which only the binaphthyl bridge has a predetermined absolute configuration R, leads to an e.e. of 83% (R-aldehyde), which is quite close to the value of 94% for (R,S)-BINAPHOS. This suggests that in the formation of the complex the binaphthyl bridge controls the conformation of the bisphenol... 

Basic rate information permits one to examine these phenomena in detail. Leighton [2], in his excellent book Photochemistry of Air Pollution, gives numerous tables of rates and products of photochemical nitrogen oxide-hydrocarbon reactions in air this early work is followed here to give fundamental insight into the photochemical smog problem. The data in these tables show low rates of photochemical consumption of the saturated hydrocarbons, as compared to the unsaturates, and the absence of aldehydes in the products of the saturated hydrocarbon reactions. These data conform to the relatively low rate of reaction of the saturated hydrocarbons with oxygen atoms and their inertness with respect to ozone. 

The central point of Evans s methodology is the induction of a 7t-enantiotopic facial differentiation through a conformationally rigid highly ordered transition state. Since the dialkylboron enolates of AT-acyl-2-oxazolidinones exhibit excellent syn-diastereoselectivity syn.anti >97 3) when reacted with a variety of aldehydes, Evans [14] studied the aldol condensation with the chiral equivalents 32 and 38. which are synthesised from fS)-valine (35) and the hydrochloride of (15, 2R)-norephedrine (36) (Scheme 9.11), respectively, and presently are commercially available. 

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