Enones chemoselectivity

Nal, CeCl3 7H20, CH3CN, rt, 0.5-21 h, 84-96% yield. Chemoselective cleavage of ketone derivatives is observed in the presence of aldehyde derivatives, and enone ketals are cleaved in the presence of simple ketone ketals. 

Reduction of carbon-carbon double bond Microalgae easily reduce carbon-carbon double bonds in enone. Usually, the reduction of carbonyl group and carbon-carbon double bond proceeds concomitantly to afford the mixture of corresponding saturated ketone, saturated alcohol, and unsaturated alcohol because a whole cell of microalgae has two types of reductases to reduce carbonyl and olefinic groups. The use of isolated reductase, which reduces carbon-carbon double bond chemoselectively, can produce saturated ketones selectively. 

An arenethiolatocopper (I) complex has been used by van Koten et al. to catalyse the 1,4-Michael addition of Grignard reagents to acyclic enones, providing the corresponding products with excellent chemoselectivities, high... 

Scheme 24) [38]. Chemoselective enolization of the less substituted enone moiety under hydrogenation conditions accompanied by subsequent aldol reaction provided the corresponding hydroxyl-enones, such as 87-89, which could be converted to various building blocks for polypropionate synthesis. p-Me2N styryl vinyl enone also was employed successfully as an enolate precursor, as demonstrated by the formation of hydroxy enone 90. 

The synthesis of 2,3,5-trialkylpyrroles can be easily achieved by conjugate addition of nitroalkanes to 2-alken-l,4-dione (prepared by oxidative cleavage of 2,5-dialkylfuran) with DBU in acetonitrile, followed by chemoselective hydrogenation (10% Pd/C as catalyst) of the C-C- double bond of the enones obtained by elimination of HN02 from the Michael adduct. The Paal-Knorr reaction (Chapter 10) gives 2,3,5-trialkylpyrroles (Eq. 4.124).171... 

Alternatively, Ballini devised a new strategy to synthesize tri-alkylated pyrroles from 2,5-dialkylfurans and nitroalkanes <00SL391>. This method involves initial oxidation of 2,5-dimethylfuran with magnesium monoperoxyphthalate to cA-3-hexen-2,5-dione (6). Conjugate addition of the nitronate anion derived from the nitro compound 7 to 6 followed by chemoselective hydrogenation of the C-C double bond of the resulting enones 8 (obtained by elimination of nitrous acid from the Michael adduct) completes the conversion to the alkylated y-diketones 9. Final cyclization to pyrroles 10 featured improved Paal-Knorr reaction conditions involving reaction of the diketones with primary amines in a bed of basic alumina in the absence of solvent. 

A ruthenium(n)-indenyl complex, which is an efficient catalyst for the isomerization of allylic alcohols, is also an effective catalyst for the isomerization of propargylic alcohols to both a,/3-enals and a,/ -enones (Scheme 57).96 In this reaction, the addition of 20—40 mol% InClj is highly effective. The reaction exhibits extraordinary chemoselectivity and a variety of functional groups are unaffected, which allows a highly efficient synthesis of dienals (R1 =Me2C = CH, R2 = H). 

Electrocatalytic hydrogenation has the advantage of milder reaction conditions compared to catalytic hydrogenation. The development of various electrode materials (e.g., massive electrodes, powder cathodes, polymer film electrodes) and the optimization of reaction conditions have led to highly selective electrocatalytic hydrogenations. These are very suitable for the conversion of aliphatic and aromatic nitro compounds to amines and a, fi-unsaturated ketones to saturated ketones. The field is reviewed with 173 references in [158]. While the reduction of conjugated enones does not always proceed chemoselectively at a Hg cathode, the use of a carbon felt electrode coated with polyviologen/Pd particles provided saturated ketones exclusively (Fig. 34) [159]. 

Chemoselectivity is often a major issue in the reduction of multifunctional organic substrates such as substituted conjugated enones. The corresponding unsaturated alcohols have found use as building blocks for pharmaceutically active molecules for example (i-amino-a-phenylethanol is used for the synthesis of (5-blockers which are the active molecules for controlling hypertension and other cardiac disorders. 

The synthesis of the non-racemic cyclopentanone (+)-93 is outlined in Scheme 15. Starting with 2-methyl-cyclopent-2-enone (90), sequential cuprate addition and enolate alkylation afforded the racemic cyclopentanone rac-92 as a single diastereomer. The double bond was cleaved by ozonolysis, the resulting aldehyde chemoselectively reduced in the presence of the keto function and the primary hydroxyl function was subsequently protected as a silyl ether to provide racemic rac-93. This sequence has been applied fre-... 

Carbenoid transformations involving competition between intramolecular cyclopropa-nation and /8-hydride elimination have been investigated149. The chemoselectivity of these catalytic transformations can be effectively controlled by the choice of catalyst. Rhodium(II) trifluoroacetate catalysed decomposition of diazoketone 111 proceeds cleanly to give only enone 112. However, rhodium(II) acetate or bis-(iV-t-butylsalicyladiminato) copper(II) cu(TBs)2 provides exclusively cyclopropanation product 113 (equation 102)149. 

The chemoselectivity in the hydrogen transfer reaction is the same already observed in H2 addition conditions in the presence of C11/AI2O3. Thus, the conjugated enone is selectively hydrogenated while the saturated keto-group remains unchanged. Also regioselectivity is the same and the olefinic bond is reduced before the carbonylic one. 

Chemoselective reduction of conjugated enones to allylic alcohols via hydrogen transfer from propan-2-ol over metal oxides is investigated in vapour phase conditions. The unique ability of Mgo to reduce exclusively carbonyl group is observed. However, because of the high basicity of MgO side reactions are present. It is shown that by doping the Mgo catalyst with HC1 a significant decrease of its basicity occurs and consequently side reactions are minimized. 

The 1,4-conjugate addition of ester enolates to a, 3-enones was first reported by Kohler in 1910,138a c as an anomalous Reformatsky reaction, but chemoselectivity was dependent on the structure of the a,(3-enone and restricted to bromozinc enolates obtained from either a-bromoisobutyrate or bromomalonate esters (Scheme 66).138d,e Further evaluation, with lithio ester enolates and lithio amide enolate additions, has resulted in identification of four factors that affect the chemoselectivity and diastereoselectivity of additions to a, 3-enones.139 These factors are (a) enolate geometry, (b) acceptor geometry, (c) steric bulk of the -substituent on the acceptor enone and (d) reaction conditions. In general, under kinetic reaction conditions (-78 °C), ( )-ester enolates afford preferential 1,2-addition products while (Z)-ester enolates afford substantial amounts of 1,4-addition products however, 1,2 to 1,4 equilibration occurs at 25 C in the presence of HMPA. The stereostructure of the 1,4-adducts is dependent on the initial enolate structure for example, with ( )-enones, (Z)-ester enolates afford anti adducts, while (E)-ester enolates afford syn adducts (Scheme 54). In contrast, amide enolates show a modest preference for anti diastereomer formation. 

---