Unsaturated aldehydes steric effects

One interesting phenomenon was the effect of the boron substituent on enantioselectivity. The stereochemistry of the reaction of a-substituted a,/ -unsatu-rated aldehydes was completely independent of the steric features of the boron substituents, probably because of a preference for the s-trans conformation in the transition state in all cases. On the other hand, the stereochemistry of the reaction of cyclopentadiene with a-unsubstituted a,/ -unsaturated aldehydes was dramatically reversed on altering the structure of the boron substituents, because the stable conformation changed from s-cis to s-trans, resulting in production of the opposite enantiomer. It should be noted that selective cycloadditions of a-unsubsti-tuted a,/ -unsaturated aldehydes are rarer than those of a-substituted a,/ -unsatu-... 

The Sorghum (S)-oxynitrilase exclusively catalyzes the addition of hydrocyanic acid to aromatic aldehydes with high enantioselectivity, but not to aliphatic aldehydes or ketones [519, 526], In contrast, the Hevea (S)-oxynitrilase was also found to convert aliphatic and a,/ -unsaturated substrates with medium to high selectivity [509, 527]. The stereocomplementary almond (R)-oxynitrilase likewise has a very broad substrate tolerance and accepts both aromatic, aliphatic, and a,/ -unsaturated aldehydes [520, 521, 523, 528, 529] as well as methyl ketones [530] with high enantiomeric excess (Table 9). It is interesting to note that this enzyme will also tolerate sterically hindered substrates such as pivalaldehyde and suitable derivatives 164 which are effective precursors for (R)-pantolactone 165 [531],... 

Figure 10.2 illustrates selected examples of these epoxide products. Aromatic and heteroaromatic aldehydes proved to be excellent substrates, regardless of steric or electronic effects, with the exception of pyridine carboxaldehydes. Yields of aliphatic and a,/ -unsaturated aldehydes were more varied, though the enantio-selectivities were always excellent. The scope of tosylhydrazone salts that could be reacted with benzaldehyde was also tested (Fig. 10.3) [29]. Electron-rich aromatic tosylhydrazones gave epoxides in excellent selectivity and good yield, except for the mesitaldehyde-derived hydrazone. Heteroaromatic, electron-poor aromatic and a,/ -unsaturated-derived hydrazones gave more varied results, and some substrates were not compatible with the catalytic conditions described. The use of stoichiometric amounts of preformed sulfonium salt derived from 4 has been shown to be suitable for a wider range of substrates, including those that are incompatible with the catalytic cycle, and the sulfide can be recovered quantitatively afterwards [31]. Overall, the demonstrated scope of this in situ protocol is wider than that of the alkylation/deprotonation protocol, and the extensive substrate...

Ketones and Aldehydes The R2C=0 and the RCH=0 carbon atoms absorb in a characteristic region. Acetone absorbs at 203.3 ppm, and acetaldehyde at 199.3 ppm. Alkyl substitution on the a-carbon causes a shift to the left of the C=0 absorption of 2-3 ppm until steric effects supervene. Replacement of the CH3 of acetone or acetaldehyde by a phenyl group causes a shift to the right of the C=0 absorption (acetophenone, 195.7 ppm benzaldehyde. 190.7 ppm) similarly, a,/3-unsaturation causes shifts to the right (acrolein, 192.1 ppm, compared with propionaldehyde, 201.5 ppm). Presumably, charge delocalization by the benzene ring or the double bond makes the carbonyl carbon less electron deficient. 

Steric and electronic effects on the photochemical reactivity of oxime acetates of p/y-unsaturated aldehydes. Journal of the Chemical Society, Perkin Transactions 1, 163-169 (b) Armesto, D., Horspool, W.M., Mancheno, M.J., and Ortiz, M.J. (1990) The aza-di-jt-methane rearrangement of stable derivatives of 2,2-dimethyl-4,4-diphenylbut-3-enal. Journal of the Chemical Society, Perkin Transactions... 

Another valuable feature of the Noyori dioxolanation is the preference for protection of a saturated ketone in the presence of an a, p-unsaturated ketone or aldehyde as illustrated in Scheme 2,29.67 However, the preference is subject to steric effects because dioxolanation of the a, P-unsaturated carbonyl of the Wieland-Miescher ketone [Scheme 230] occurs selectively (see Scheme 2,22) and there is a further bonus the double bond did not rearrange out of conjugation as it is wont to do under certain traditional acid-catalysed conditions (see below).6 ... 

Ketones are less reactive than aldehydes because the inductive and steric effects of the second alkyl group make the carbonyl group less susceptible to nucleophilic attack. Nevertheless, acetone can be induced to react and an equilibrium (see Scheme 3.80) can be estabhshed. Depending on the base, elimination of water may take place to give an unsaturated ketone. A second condensation may also take place to form phorone (2,6-dimethyl-4-oxohepta-2,5-diene). 

The exceptionally bulky Lewis acid MAD has a distinct steric effect on stereoselectivity in the Diels-Alder reaction of cyclic dienes and a,/3-unsaturated aldehydes, as exemplified by the MAD-mediated highly exo-selective cycloaddition of methacrolein and cyclopentadiene (Sch. 130) [169],... 

The continued search for methods to effect lj4-reductions using catalytic quantities of CuH produced several reports late in the last decade. The basis for these new developments lies in an appreciation for the fadlitj with which various silyl hydrides undergo transmetalation vdth copper enolates. Thus a limited amount of (PhjP)CuH (0.5-5 mol%) in the presence of PhSiHj (1.5 equivalents relative to substrate) reduces a varietj of unsaturated aldehydes and ketones in high yields (Eq. 5.14) [29]. Limitations exist with respect to the extent of steric hindrance in the educt Similar results can be achieved using BusSnH in place of PhSiHj although the latter hydride source is the appropriate (albeit expensive) choice from the environmental perspective. 

Reduction of tosyl- and trisylhydrazones.3 The reagent (1 equivalent) reduces tosylhydrazones of ketones to alkanes in yields of 60-85% (GLC). The reduction is lubject to steric hindrance and so is not effective with the tosylhydrazone of camphor. Tosylhydrazones of aldehydes are reduced in moderate yield (about 50%). The reagent does not reduce tosylhydrazones of aromatic or a,/ -unsaturated aldehydes or ketones. 

From these findings, it can be concluded that the structure sensitivity in the selective hydrogenation of a,p unsaturated aldehydes such as crotonaldehyde and cinnamaldehyde largely depends on the steric effect of the bulky substituent on P-carbon of the substrate, but that another interpretation, e.g., an electronic effect, should be proposed for the size effect in the hydrogenation of acrolein. 

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