Unsaturated aldehydes selective

HS(CH2) SH, BF3-Et20, CH2CI2, 25°, 12 h, high yield, n = 2, n = 3. In a,/3-unsaturated ketones the olefin does not isomerize to the /3,7-position as occurs when an ethylene ketal is prepared. Aldehydes are selectively protected in the presence of ketones except when steric factors force the ketone to be protected as in the example below." A TBDMS group is not stable to these conditions. ... 

Unsaturated aliphatic aldehydes were selectively reduced to unsaturated alcohols by specially controlled catalytic hydrogenation. Citral treated with hydrogen over platinum dioxide in the presence of ferrous chloride or sulfate and zinc acetate at room temperature and 3.5 atm was reduced only at the carbonyl group and gave geraniol (3,7-dimethyl-2,6-octadienol) [59], and crotonaldehyde on hydrogenation over 5% osmium on charcoal gave crotyl alcohol [763]. 

Propanol doped on dehydrated alumina reduces various aldehydes and ketones at room temperature to the corresponding alcohols. a,p-Unsaturated aldehydes are selectively reduced under these conditions to the corresponding allylic alcohols. For example, citral is converted to geraniol in 88% yield. a,p-Unsaturated nitriles are reduced to saturated nitriles with triethylamine-formic acid azeotrope in... 

Reactivities and yields are said to increase with increasing size of the alkyl group of the aldehyde.89 Addition to, / -unsaturated aldehydes occurs selectively to the carbonyl group,91 this behavior differing from that of ,/J-unsaturated ketones (cf. page 695) of the unSaturated ketones it is only those, such as mesityl oxide, that carry two alkyl groups at the -position, that add phosphites to the carbonyl group.93... 

As mentioned above, although some examples of intramolecular MBH reactions have been reported in the literature, this aspect is still in its infancy. Most known reports are based on the cyclizations of combinations of enone-enone, enone-acrylate, enone-aldehyde, unsaturated thioester-aldehyde, enone-allylic carbonate frameworks, etc. More recently, Krafft et al. have developed a novel, entirely organo-mediated intramolecular MBH reaction by using allyl chloride 277 as an alternative electrophile to afford densely functionalized cyclic enones 278. This reaction tolerates modification of the enone and the use of primary and secondary allylic chlorides and generates both five-and six-membered rings in excellent yields. Both mono- and disubstituted alkenes are formed with excellent selectivity in the absence of a transition metal catalyst (Scheme 1.100). ... 

The representative 2-alkenal adducts are summarized in Figure 6.4. The reactions of lysine with 2-alkenals have been mainly studied with acrolein, crotonaldehyde, and 2-nonenal. Similar to other a,P-unsaturated aldehydes, acrolein selectively reacts with the cysteine, histidine, and lysine residues of proteins. The primary products are their 3-substituted propanals (1) (Figure 6.4a). These p-substituted propanals or Schiff s base crosslinks had been suggested as the predominant acrolein-lysine adducts however, the major product formed upon the reaction of acrolein with a protein was identified to be a novel lysine product, A -(3-formyl-3,4-dehydropiperidino) lysine (FDP-lysine) (2), which requires attachment of two acrolein molecules to one lysine side chain (Uchida et al, 1998b). This and the fact that crotonaldehyde also forms a similar FDP-type adduct, A -(2,5-dimethyl-3-formyl-3,4-dehydropiperidino) lysine (dimethyl-FDP-lysine) (Ichihashi et al., 2001), suggest that this type of condensation reaction is characteristic of the reaction of 2-alkenals with primary amines. Indeed, upon reaction with a lysine derivative, other 2-alkenals, such as... 

Terpene-derived bis-N-oxide 21.22 represent the most recent addition to the successful catalyst series. The catalyst was shown to be particularly efficient in the allylation and crotylation of aromatic and a,p-unsaturated aldehydes (<99% enantiomeric excess at —60°C), however, with aliphatic aldehydes the selectivity dropped to 50% ee. It is noteworthy that 21.22 was synthesised in four easy steps from inexpensive (I )-myrtenal and the protocol is amendable to scaling up. In contrast, synthesis of enantiopure catalysts 21.19-21.21 requires either resolution of enantiomers or separation of diastereoisomeric mixtures, which hampers their larger-scale application. In this group of polydentate IV-oxides it is also worth mentioning terpyridine N,IV IV"-trioxide, the related bis-imidazole Af,M -dioxides and chiral dinitrones,but their efficiency was inferior to the best pyridine-type dioxides, such as 21.20-21.22. 

The most commonly used protected derivatives of aldehydes and ketones are 1,3-dioxolanes and 1,3-oxathiolanes. They are obtained from the carbonyl compounds and 1,2-ethanediol or 2-mercaptoethanol, respectively, in aprotic solvents and in the presence of catalysts, e.g. BF, (L.F. Fieser, 1954 G.E. Wilson, Jr., 1968), and water scavengers, e.g. orthoesters (P. Doyle. 1965). Acid-catalyzed exchange dioxolanation with dioxolanes of low boiling ketones, e.g. acetone, which are distilled during the reaction, can also be applied (H. J. Dauben, Jr., 1954). Selective monoketalization of diketones is often used with good success (C. Mercier, 1973). Even from diketones with two keto groups of very similar reactivity monoketals may be obtained by repeated acid-catalyzed equilibration (W.S. Johnson, 1962 A.G. Hortmann, 1969). Most aldehydes are easily converted into acetals. The ketalization of ketones is more difficult for sterical reasons and often requires long reaction times at elevated temperatures. a, -Unsaturated ketones react more slowly than saturated ketones. 2-Mercaptoethanol is more reactive than 1,2-ethanediol (J. Romo, 1951 C. Djerassi, 1952 G.E. Wilson, Jr., 1968). 

Ailyl enol carbonates derived from ketones and aldehydes undergo Pd-cat-alyzed decarboxylation-elimination, and are used for the preparation of a, /3-unsaturated ketones and aldehydes. The reaction is regiospecific. The regio-isomenc enol carbonates 724 and 726, prepared from 723, are converted into two isomeric enones, 725 and 727. selectively. The saturated aldehyde 728 can be converted into the a,/3-unsaturated aldehyde 730 via the enol carbonate 729[459]. 

A particularly useful reaction has been the selective 1,2-reduction of a, P-unsaturated carbonyl compounds to aHyUc alcohols, accompHshed by NaBH ia the presence of lanthanide haUdes, especially cerium chloride. Initially appHed to ketones (33), it has been broadened to aldehydes (34) and acid chlorides (35). NaBH by itself gives mixtures of the saturated and unsaturated alcohols. 

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-... 

Among the many chiral Lewis acid catalysts described so far, not many practical catalysts meet these criteria. For a,/ -unsaturated aldehydes, Corey s tryptophan-derived borane catalyst 4, and Yamamoto s CBA and BLA catalysts 3, 7, and 8 are excellent. Narasaka s chiral titanium catalyst 31 and Evans s chiral copper catalyst 24 are outstanding chiral Lewis acid catalysts of the reaction of 3-alkenoyl-l,2-oxazolidin-2-one as dienophile. These chiral Lewis acid catalysts have wide scope and generality compared with the others, as shown in their application to natural product syntheses. They are, however, still not perfect catalysts. We need to continue the endeavor to seek better catalysts which are more reactive, more selective, and have wider applicability. 

Below is a table of asymmetric Diels-Alder reactions of a,/ -unsaturated aldehydes catalyzed by chiral Lewis acids 1-17 (Fig. 1.10, 1.11). The amount of catalyst, reaction conditions (temperature, time), chemical yield, endojexo selectivity, and optical purity are listed (Table 1.32). 

---