2-Cyclohexenone addition with

A comparison of the configuration of the substrates and reaction products shows that the oxiranyl anions arc configurationally stable under the reaction conditions. Only one example is known in which isomerization was observed. When the ci.v-tm-butyl-substituted epoxysilane27 was metalated and quenched with 2-cyclohexenone, addition product 27 was obtained under inversion of the anionic center. Presumably the strain created in forcing the ter/-butyl and the trimethylsilyl group cis on the oxirane ring facilitates the isomerization process13. 

Using 3-substituted cyclohexanones the /rans-diastereoselective synthesis of decalones and octahydro-1 //-indenones may be achieved 164 169. This method has been applied, for instance, in the synthesis of 19-norsteroids. In a related Michael addition the lithium enolate of (R)-5-trimethylsilyl-2-cyclohexenone reacts with methyl 2-propenoate selectively tram to the trimethylsilyl substituent. Subsequent intramolecular ring closure provides a single enantiomer of the bicyclo[2.2.2]octane170 (see also Section 1.5.2.4.4.). 

In 1997, Miyaura and co-workers reported the nonasymmetric version of 1,4-addition of aryl- and alkenylboronic acids to a,/ -unsaturated ketones using rhodium-phosphine complex as the catalyst.97 Later, Hayashi and Miyaura realized the asymmetric 1,4-addition with high catalytic activity and enantioselectivity.98 In the presence of ( y)-BINAP, the reaction of 2-cyclohexenone with 2.5 equiv. of phenylboronic acid gave (A)-3-phenylcyclohexanone with 97% ee (BINAP = 2,2 -bis (diphenylphosphino)-l,l -binaphthyl Scheme 29).99... 

The cuprate derived from the cis isomer of this reagent undergoes conjugate addition with cyclohexenone with unusually high diastereoselectivity (5 1, Eq. 23)24). In this case, electrophilically initiated ring opening with mercuric acetate chemo-selectively attacks the sterically least hindered cyclopropyl bond to give a branched product 7. Reductive work-up produces 8 in which the stereochemistry of the... 

A breakthrough was achieved with chiral phosphoramidite (S, R, i )-18, in which a C2-symmetric (S)-binaphthyl unit and a C2-symmetric (R, R)-bis-(l-phenylethyl)-amine unit are present (Scheme 7.10), resulting in the enantioselective catalytic 1,4-addition of Et2Zn to 2-cyclohexenone (6) with >98% ee [38]. 

In an ideal kinetic resolution (common in enzyme-catalyzed processes), one enantiomer of a racemic substrate is converted tvhile the other is unreactive [70]. In such a kinetic resolution of 5-methyl-2-cyclohexenone, even with 1 equivalent of Me2Zn, the reaction should virtually stop after 50% conversion. This near perfect situation is found with ligand 18 (Fig. 7.10) [71]. Kinetic resolutions of 4-methyl-2-cyclohexenone proceed less selectively (s = 10-27), as might be expected from the lower trans selectivity in 1,4-additions to 4-substituted 2-cyclohexenones [69]. 

After the 2-cyclohexenone addition was complete, the 100-mL, round-bottomed flask was washed with 10 mL of anhydrous tetrahydrofuran, and this wash was cannulated into the 500-mL flask (Note 2). 

Chiral -substituted ketones Conjugate addition of (CH,)iAI to the kctal (2) of cyclohexenone derived from (S,S)-1 followed by acetylation results in the adduct 3, which is hydrolyzed by acid to (S)-3-mcthylcyclohcxanonc (4) in 77% ee. The ketal derived from (2R,3R)-2,3-butanediol undergoes a similai conjugate addition with low a.symmetric... 

Tlie latter reagent undergoes 1,2-addition to a,p-unsaturated aldehydes 1,4-addition, with copper catalysis, is observed with cyclohexenone alone. A more satisfactory reagent for the conjugate introduction of the hydroxymethyl group is the allyldimethylsilylmethyl Grignt reagent... 

Steric interactions can dramatically affect regioselectivity as well. This is demonstrated by the result that cyclohexenone reacts with vinyl acetate to give exclusively the head-to-tail regioisomer (9) while 3-methylcyclohexenone produces a 1 4 mixture of the head-to-head head-to-tail isomers (10) (11) (equation 8). Additionally, 3-n-butylcyclopentenone undergoes photocycloaddition with vinyl acetate to give a 3 1 mixture of head-to-tail head-to-head photoadducts while 1-acetoxy-l-hexene gives rise to exclu-... 

A similar highly stereoselective Michael addition has been reported by Uda. The enolate of a substituted cyclohexenone reacted rapidly in a Michael-type addition with methyl a-thiophenylmethacrylate... 

Diastereoselective addition to 4-substituted 2,3-didehydropyroglutamate esters reveals the entry cis to the ester group. Unexpectedly, 5-(/-butyldimethylsiloxy)-2-cyclohexenone reacts with MeCu(CN)Li in a cis-selective manner (cisUrans >99 I)." ... 

The synthesis presents two points of interest. It provides a method for synthesis of 2-alkylcyclopentenones. It also provides a method for addition of the unit CH2COOCH3 to electrophilic olefins. Thus the reaction of 2-cyclohexenone (9) with (6) followed by the steps outlined above leads to the keto ester (10) in 55 % yield. 

Preparation of diethyl 3-oxoalkylphosphonates using the copper-zinc reagents derived from diethyl 2-bromoethylphosphonate can be extended to diethyl 5-oxoalkylphosphonates. Effectively, these copper-zinc reagents have been found to react with cyclohexenone and benzylideneacetone in the presence of Me3SiCl to give the 1,4-addition products in satisfactory yields (71-88%). 3-lodo-2-cyclohexenone reacts with tlie copper-zinc reagents to give the addition-elimination product in 86% yield. 

Electron-rich alkenes are often used as addends for this type of cycloaddition. As described by R. Neier a cyclic P-amido cyclohexenone (compare with the open-chain substrate before) undergoes clean [2+2] cycloaddition to tetramethylethylene. Additionally a useful method for the enhancement of diastereomeric purity is described. Many starting materials, which are used for [2+2] photocycloaddition reactions, are protected enols of... 

Dicarbonyl compound 52 being strongly acidic undergoes a Michael addition with methyl vinylketone (MVK) and the intermediate products can be cyclized to s/wVo-cyclohexenone 68 (Scheme 64, ref. 65). 

Another difference in the reactivity of these two ylids is reflected in their reactions with a, 3-unsaturated ketones. The carboethoxy dimethylsulfonium methylid 620 reacted with cyclohexenone to give the usual alkoxy sulfonium salt 621. Intramolecular displacement of dimethyl sulfide led to the expected oxirane (622) analogous to the formation of 614. Dialkylsulfonium ylids react via 1,2-addition with displacement of the... 

In Chapter 19 (Section 19.2), lithium aluminum hydride and sodium borohydride reacted with ketones or aldehydes via acyl addition to reduce the carbonyl to the corresponding alcohol. This reaction is complicated by the presence of a conjugating n-bond. When cyclohexenone reacts with LiAlH4, the product is a mixture of cyclohexenol (66) and cyclohexanol (67). Cyclohexenol results from 1,2 addition of the hydride, but 67 results from 1,4 addition and 1,2 addition. 

This cuprate also underwent the conjugate addition with acyclic enones, for example, 2-hexene-4-one, to give 5-methyl-3-tridecanone in 47% yield. We have not attempted further optimization. Reaction of this calcium cuprate with a sterically hindered enone, for example, isophorone, produced <3% of the desired compound in 24h. The isolated yield, however, increased to 84% when the additives BF3 etherate and chlorotrimethylsilane [12] were used. In the aryl case, / -tolylcalcium cuprate also underwent this transformation with 2-cyclohexenone to give 3-(p-methylphenyl)cyclohexanone in reasonable yield (Table 9.3). 

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