2-Cycloalkenone, 2- addition reaction

The addition reaction of the lithium salt of ( + )-3-[(7 )-4-methylphenylsulfinyl]-l-propene with various 2-cycloalkenones was examined at —78 DC in tetrahydrofuran17. 

A different approach towards titanium-mediated allene synthesis was used by Hayashi et al. [55], who recently reported rhodium-catalyzed enantioselective 1,6-addition reactions of aryltitanate reagents to 3-alkynyl-2-cycloalkenones 180 (Scheme 2.57). In the presence of chlorotrimethylsilane and (R)-segphos as chiral ligand, alle-nic silyl enol ethers 181 were obtained with good to excellent enantioselectivities and these can be converted further into allenic enol esters or triflates. In contrast to the corresponding copper-mediated 1,6-addition reactions (Section 2.2.2), these transformations probably proceed via alkenylrhodium species (formed by insertion of the C-C triple bond into a rhodium-aryl bond) and subsequent isomerization towards the thermodynamically more stable oxa-jt-allylrhodium intermediates [55],... 

The 1,4-addition of selenophenols to cycloalkenones proceeds smoothly under the same conditions used in the thiophenol addition (see Section V) (eq. [18]). Although the e.e. of the products is 40 to 65%, compared with the 60 to 80% achieved in the thiol addition reaction, the solid adducts are readily purified to enantiomeric purity by crystallization (63). 

Chiral Ligand for other Stereoselective Reactions. The effect of the addition of dihydroquinidine-derived alkaloids on the product enantioselectivity has also been investigated in the addition reaction of Diethylzinc to aldehydes, in the addition of aromatic thiols to conjugated cycloalkenones, and in the heterogeneous hydrohalogenation of a,a-dichlorobenzazepinone-2. In these cases, the dihydroquinidine derivatives were not the optimal ligands. 

Catalytic, Enantioselective Addition of Arylboronic Acids to Cycloalkenones. A complex between ligand 1 and a rhodium(I) salt was found to catalyze the asymmetric 1,4-addition reaction of arylboronic acids to cyclohexenone and cyclohep-tenone. The reaction proceeds with high enantiocontrol and excellent yields (eq 4). Lower enantiomeric excesses were observed with cyclopentenone (83% ee), but a variety of substituted phenyl-boronic acids could be used. 

The same type of process using osmylation instead of the Simmons-Smith reaction leads to a synthesis of enantiomerically pure 2,3-dihydroxycycloalkanones from 2-cycloalkenones. Addition of (S)-(141) to 3,S,S-trimethyl-2-cyclohexenone (162) produces a mixture of diastereomers (163a) and (163b), which are easily separable by silica gel chromatography. Treatment of the individual diastereomers with tri-ethylamine N-oxide and 0s04 (5 mol %) afford crude triols. In each case, a single diastereomeric product is produced. The subsequent thermolysis of the diastereomeric triols gives enantiomeric 2,3-dihydroxy-3,5,5-trimethyl-2-cyclohexanones(164 Scheme 37). 

Sparteine 7 is also an excellent chiral ligand for the asymmetric Michael addition of chirally fixed organolithiums (Eq. (12.8)) [25]. The choice of ligand for the lithium cation provides control of 1,2- vs 1,4-addition of organolithium species to cycloalkenones. Furthermore, in these addition reactions, two contiguous stereocenters were constructed with high diastereo- and enantioselectivities. 

In the case of cycloheptenone and larger rings, the main initial photoproducts are the fran.r-cycloalkenones produced by photoisomerization. In the case of the seven-and eight-membered rings, the fran -double bonds are sufficiently strained that rapid reactions follow. In nonnucleophilic solvents dimerization takes place, whereas in nucleophilic solvents addition reactions occur. ... 

One of the processes available to electronically excited enones is isomerization about the carbon-carbon double bond. Cis cycloalkenones with seven or eight atoms can undergo photoisomerization to strained trans cycloalkenones. In turn, the trans double bond can undergo addition reactions with alcohols or amines. For example, irradiation (350 nm) of cyclohept-2-enone (90) in acetonitrile containing benzimidazole led to a 94% conversion to 3-(lH-benzo[d]imidazol-l-yl)cycloheptanone (91, equation 12.68). ... 

In 1981, Wynberg and Hiemstra already identified the unmodified cinchona alkaloids as chiral bifunctional catalysts for enantioselective conjugate additions to cycloalkenones [3]. They proposed that the OH group of cinchonine would act as a hydrogen bond donor site and stabilize the enolate-Uke transition state of the conjugate addition reaction (Scheme 6.1). 

Four-component annelation to alkenolides. Posner et al. have reported a one-pot three-step annelation of cycloalkenones to provide, after oxidation, four-atom enlarged macrolides. Thus Michael addition of tributyltinlithium to cyclo-hexenone (1) and Michael addition of the resulting enolate to ethyl vinyl ketone followed by an aldol reaction results in cyclization to a bicyclic hemiketal (2), which is oxidized by Pb(OAc)4 to an unsaturated 10-membered lactone (3). 

This preparation illustrates an efficient two-step process for the transformation of a cycloalkenone to the corresponding a-substituted derivative. The first step involves the installation of an a-iodo substituent by a process thought to involve nucleophilic addition of pyridine, iodine capture of the resulting enolate, and pyridine-promoted elimination of pyridine.5 The resulting vinyl iodides are superior to other vinyl halides as participants in a variety of transition-metal catalyzed coupling reactions, illustrated here by the Suzuki coupling with an arylboronic acid. Other coupling partners that... 

The synthetic implications of this discovery were slow to be exploited. Base-initiated dimerizations of 2-cycloalkenones, known to give crystalline solids,3233 remained puzzling for some time before conjugate additions were suggested to account for some of the possible products 34 indeed, the product of base-catalyzed dimerization of 4,4-dimethyl-2-cyclopentenone, which proceeds via a double Michael addition sequence, was not identified until 1969 (Scheme 2).35 An unanticipated cyclopropanation reaction of acrylaldehyde36 37 using ethyl bromomalonate and proceeding by means of a similar Michael addi-tion-Sw enolate alkylation represents an early synthetic use of tandem vicinal difunctionalization. 

The heterobimetallic multifunctional complexes LnSB developed by Shibasaki and Sasai described above are excellent catalysts for the Michael addition of thiols [40]. Thus, phenyl-methanethiol reacted with cycloalkenones in the presence of (R)-LSB (LaNa3tris(binaphthox-ide)) (10 mol %) in toluene-THF (60 1) at -40°C, to give the adduct with up to 90% ee. A proposed catalytic cycle for this reaction is shown in Figure 8D.9. Because the multifunctional catalyst still has the internal naphthol proton after deprotonation of the thiol (bold-H in I and II), this acidic proton in the chiral environment can serve as the source of asymmetric protonation of the intermediary enolate, which is coordinated to the catalyst II. In fact, the Michael addition of 4-/en-butylbenzcnethiol to ethyl thiomethacrylate afforded the product with up to 93% ee using (R)-SmSB as catalyst. The catalyst loading could be reduced to 2 mol % without affecting enantioselectivity of the reaction. 

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