Carbonyl-ene-type reaction

Carreira et al. used a chiral BlNOL-derived Schiff base-titanium complex as the catalyst for the aldol reactions of acetate-derived ketene silyl acetals (Scheme 8C.29) [64a]. The catalyst was prepared in toluene in the presence of salicylic acid, which was reported to be crucial to attain a high enantioselectivity. A similar Schiff base-titanium complex is also applicable to the carbonyl-ene type reaction with 2-methoxypropene [64b], Although the reaction, when con-... 

A nickel hydride complex, NiHCl(diphenylphosphinoethane), catalyses the tandem isomerization-aldolization reaction of allylic alcohols with aldehydes.156 The atom- (g) efficient process proceeds at or below ambient temperature with low catalyst loading, and works well even for bulky aldehydes. Magnesium bromide acts as a co-catalyst, and mechanistic investigations suggest that a free enol is formed, which then adds to the aldehyde in a hydroxyl-carbonyl-ene -type reaction. 

This section deals with oxidation reactions as an initiative step of the domino process in combination with many other organic transformations. In 2004, Snaith and coworkers [3] demonstrated a simple and efficient method to synthesize 3-substituted 4-piperidinones 4 using a domino oxidation/carbonyl-ene/oxidation reaction (Scheme 9.1). This domino reaction comprises oxidation of unsaturated alcohol 1 using PCC (pyridinium chlorochromate) to give the corresponding aldehyde 2, followed by a carbonyl-ene type reaction to yield the secondary cyclic alcohol 3, which was oxidized under the reaction conditions to give 3-substituted 4-piperidinones 4 in good yields. 

Ng, T. F. Jamison, J. Am. Chem. Soc. 2006, 128, 5362-5363. Nickel-catalyzed, carbonyl-ene-type reactions selective for alpha olefins and more efficient with electron-rich aldehydes, (c) C.-Y. Ho, T. F. Jamison, Angew. Chem. Int. Ed. 2007, 46, 782—785. Highly selective coupling of alkenes and aldehydes catalyzed by [Ni(NHC) P(OPh)j ] synergy between a strong a donor and a strong k acceptor. 

Reactions of the allylic position of alkenes with carbonyl or imine electrophiles are known as Prins reactions and have been discussed in previous sections (3.2.9). More examples of similar Alder-ene-type reactions (the Prins reaction) will be discussed in Chapter 8. 

The reaction shown in equation 170 is, however, the only known example where a silene reacts with its acylpolysilane precursor. Whereas sUenes of the type (Me3Si)2Si=C(OSiMe3)R do not react with their polysUane precursors, they readily react with less sterically congested acylsilanes. Thus, mesitylsilene 349 gives with benzoyl trimethylsilane a mixture of the diastereomeric sUoxetanes /Z-511 in 95% yield (equation 171). Typically, the adamantylsilene 150 gives with benzoyl trimethylsilane the nominal [4 + 2] cycloadduct 512 in 89% yield (equation 172). The silyl enol ether 513 is the result of an ene -type reaction which occnrs between 150 and acetyl triphenylsilane, a carbonyl compound having an activated hydrogen (eqnation 173). ... 

Type I and II silicon-tethered carbonyl-ene reactions were first performed by Robertson.4,4a,4b One particularly striking application of this method is the conversion of isoserine derivative 3 (Scheme 1) into amino triol 4 via a carbonyl-ene reaction followed by Tamao-Fleming oxidation.5... 

The carbonyl group in a ketone or aldehyde is an extremely versatile vehicle for the introduction of functionality. Reaction can occur at the carbonyl carbon atom using the carbonyl group as an electrophile or through enolate formation upon removal of an acidic proton at the adjacent carbon atom. Although the carbonyl group is an integral part of the nucleophile, a carbonyl compound can also be considered as an enophile when involved in an asymmetric carbonyl-ene reaction or dienophile in an asymmetric hetero Diels-Alder reaction. These two types of reaction are discussed in the next three chapters. 

Reactions where NLE have been discovered include Sharpless asymmetric epoxi-dation of allylic alcohols, enantioselective oxidation of sulfides to sulfoxides, Diels-Alder and hetero-Diels-Alder reactions, carbonyl-ene reactions, addition of MesSiCN or organometallics on aldehydes, conjugated additions of organometal-lics on enones, enantioselective hydrogenations, copolymerization, and the Henry reaction. Because of the diversity of the reactions, it is more convenient to classify the examples according to the types of catalyst involved. 

Mikami et al. reported the first examples of catalytic asymmetric intramolecular carbonyl-ene reactions of types (3,4) and (2,4), using the BINOL-derived titanium complex (1) [46,49], The catalytic 7-(2,4) carbonyl-ene cyclization gives the corresponding oxepane with high enantiopurity, and the gem-dimethyl groups are not required (Scheme 8C.I8). In a similar catalytic 6-(3,4) ene cyclization, tran.v-tetrahydropyran is preferentially obtained with high enantiopurity (Scheme 8C. 19), The sense of asymmetric induction is the same as that observed for the glyoxylate-ene reaction, that is, (R)-BINOL-Ti catalyst provides (R)-alcohol. Therefore, the... 

Scheme 8C.27. Asymmetric carbonyl-ene rr. aldol-type reaction of a-benzyloxy aldehyde.

Figure 8C.9. Transition states of carbonyl-ene and aldol-type reaction of a-alkoxy aldehyde.

The ene reaction is the major side reaction in the Sakurai-Hosomi coupling reaction. Thus, treatment of 221 with carbonyl or with azo compounds in the presence of TiCl2(OPr-/)2 furnishes a mixture of ene-type product 222 and the Sakurai-Hosomi-type product 223 (equation 182)327. Allylsilylation of alkenes328 and alkynes329-330 proceeds regioselectively to give 224 (equation 183) and 225 (equation 184), respectively when aluminum catalysts are used. 

A useful synthetic alternative to the Mukaiyama aldol addition is the carbonyl-ene reaction [17], This reaction of an aldehyde 51 with an enol ether 55, bearing at least one hydrogen atom in the allylic position, under Lewis-acid catalysis, yields a ff-hydroxy-enol ether of type 56 (Scheme 10). By use of a chiral Lewis acid (L ) enantioselectivity can be achieved. For the... 

Alkynols complexed to cobalt can be oxidized to alkynals without decomplexation. Propargyl aldehydes are protected from polymerization upon complexation with Co2(CO)6. These aldehydes smoothly undergo Wittig-type reactions. Carbonyl-ene reactions have been demonstrated (Scheme 194). Complexation to cobalt protected the enyne in complex (132) from Michael-type reactions (Scheme 195). Alkenyl-substituted complexes undergo [3 + 2]cycloadditions with nitrile A-oxides (Scheme 196). 

Lewis acid-mediated rearrangement of enol ethers affords 1,2-disubstituted cycloaUcanones with high stereoselectivity (Scheme 234). Related reactions of dichloro-substituted enol ethers afford 2,2-dichloro-substituted cycloaUcanones (Scheme 235). When titanium tetrachloride was used as the Lewis acid, a carbonyl-ene Prince-type reaction can take place (Scheme 236). 

Ene Cyclization, " The asymmetric catalysis of the intramolecular carbonyl-ene reaction not only of type (3,4) but also (2,4) employs the BINOL-derived titanium complexes [(I )-BINOL-TiX2 X = C104 or OTf], modified by the perchlorate and trifluoromethanesulfonate ligands. The tmns-... 

The synthetic potential of the asymmetric catalytic carbonyl-ene reaction depends greatly on the functionality possible in the carbonyl enophile. The types of enophile that can be employed in the asymmetric catalytic ene reaction have, however, previously been limited to aldehydes such as glyoxylate [49,51-53,55,56] and chloral [50,57]. It is, therefore, highly desirable to develop other types of carbonyl enophile to provide enantio-enriched molecules with a wider range of functionality. We have thus developed an asymmetric catalytic fluoral-ene reaction [58], which is... 

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