Jacqueline Seyden-Penne

Factors controlling the regioselectivity of additions to α-enones—VI: Reactions of acetonitrile and phenylacetonitrile anions

Abstract Reaction of α-enones 1a-g with acetonitrile anion 5 , in THF at −80° gives, irreversibly, alcohols 7 or 11 , resulting from carbonyl carbon attack, whatever the associated cation is (K + or Li + ). The reaction is considered to be under charge control. In THF, lithiated phenylacetonitrile 6 gives the alcohols 8 and 12 under kinetic control with benzalacetone 1b , 2-cyclohexenone 1d and 3-methyl 2-cyclohexenone 1e . Lithium alcoholate formation is reversible and ketones 10b, 14a and 14b formation, resulting from carbon 4 attack, is thermodynamically controlled. The other α-enones studied lead, under the same reaction conditions, to ketones 10a, 10c, 14c and 14d only. In a THF-HMPA mixture, reagent 6 only gives the starting α-enone, ketones 10 and 14 . The lower lying the α-enone LUMO level, the faster the reaction, which indicates, in the present case, that the transition state for carbon carbon double bond attack occurs relatively early in the reaction path.

Factors controlling the regioselectivity of additions to α-enones—III: Reactions of 3-aryl α-enones with phosphorylated anions

Abstract Reaction of phosphonoester 2 and phosphononitrile 3 with chalcone and p -methoxychaleone in THF-t-BuOK at room temperature gives only the product resulting from CC double bond attack. The same reagents with benzalacetone lead to mixture of products resulting from CC double bond and carbonyl attack, though phosphine oxide 4 gives only the products of CC attack. Dypnone gives products of carbonyl attack with 3 and does not react with 2 . These results are discussed in terms of perturbation theory: C 4 attack increases with delocalization of the reagents negative charge and lowering of the α-enone LUMO level.

Factors controlling the regioselectivity of additions to α-enones—IV: Reactions of 3-alkyl and alicyclic α-enones with phosphorylated anions

Abstract Reaction of phosphonoester ( 2 ) and phosphononitrile ( 3 ) with 3-alkyl or alieyclic α-enones in THF—t-BuOK gives different products resulting mainly from primary CC double bond attack. The reaction is very fast, compared with 3-aryl substituted analogs. These results are interpreted in terms of a transition state for which deconjugation (π energy loss due to hybridization change of reagent) has to be taken into account in addition to HOMO-LUMO interactions. A 3,3-disubstituted α-enone reacts slowly with phosphonitrile ( 3 ) at the carbonyl carbon, CC double bond attack being inhibited by steric hindrance. These results indicate the limitation of perturbation theory which only applies with certainty for very early transition states.

The influence of lithium complexing agents on the regioselectivity of reductions of substituted 2-cyclohexenones by LiAlH4 and LiBH4

Abstract A reversal of regioselectivity of LiAlH4 or LiBH4 reduction of 2-cyclohexenone induced by addition of [2.1.1]-cryptand to the reaction medium is accompanied by a rate decrease. In the absence of the cryptand, carbonyl attack predominates (C1:C3 = 86:14 with LiAlH4 in THF). In the presence of the cryptand, double bond attack is favoured (C1:C3= 14:86). This effect is larger with LiAlH4 than with LiBH4. This trend is general in the case of five substituted 2-cyclohexenones. Using 12-crown-4 as a Li+ coordinator, a change in regioselectivity occurs but it is less pronounced than with the cryptand.

Stereochemistry of the aldol condensation of benzaldehydes with alpha-chloro esters : An example of the gauche effect of adjacent polar bonds

Abstract Under irreversible conditions, the stereochemical course of the aldol condensation of benzaldehydes with esters R 1 CHClCO 2 R (R 1 = H or Me) in the presence of NaH, NaOR or KOR depends only on the nature of R. Solvent and temperature have negligible effects. The reaction has been performed with eight ortho - or para -substituted benzaldehydes; only in the case of o -methoxybenzaldehyde has a different stereochemical result been obtained. Possible transition states for the Darzens reaction are discussed and it is shown that all of the data are consistent with a mechanism involving addition of a pyramidal carbanion to the aldehyde CO group via the rotameric forms predicted on the basis of the gauche effect

Addition conjuguée dans le thf-hmpt d'arylacétonitriles lithies aux cyclohexèn-2 ones substituées: intervention des facteurs stériques et électroniques

Abstract The reaction of lithiated arylacetonitriles 2a -c with 2-cyclohexenones 3-9 in THF-HMPA (80:20 v/v) at −70° leads in all cases but one to δ-ketoalkylnitriles, resulting from 1,4-addition. The only case where some 1,2-addition takes place is the reaction of 2a with 4,4-dimethyl 2-cyclohexenone 7. The formation of allylic alcoholates, products of 1,2-addition, is shown to be reversible in this solvent mixture. However, in several cases, kinetic control of 1,4-addition is demonstrated. The rate of formation of 1,4-addition products depends upon the arylacetonitrile substituents: 2a > 2b > 2c (i.e. the higher lying the nucleophile HOMO the faster the reaction). It is also sensitive to the cyclohexenone substituents; although methyl on C-2 and gem-dimethyl on C-5 or t-butyl on C-4 have small influence on the reaction rate, methyl on C-3 or gem dimethyl on C-4 induce a noticeable rate decrease. The addition, of 2b on 4-t-butyl 2-cyclohexenone 8 leads, at the early stage, to a predominating isomer 15b , to which the trans diaxial configuration of the substituents has been attributed by 250 MHz 1 H NMR. A single transition state model, reagent-like, where the nucleophile approaches the C-C bond by the less hindered face of the 2-cyclohexenone in a 1,2-diplanar conformation, the CN substituent being directed towards the C=0 group, accounts for all the substituent effects and the stereoselectivity observed.

Addition of lithiated anions from arylacetonitriles to α,β-unsaturated aldehydes: solvent effect on 1,2 versus 1,4 addition under kinetic and/or thermodynamic control

Abstract In THF at −70°C lithiated anions from arylacetonitriles undergo exclusively 1,2 addition to α,β-unsaturated aldehydes under kinetically controlled conditions, while 1,4 addition can be observed in some cases under thermodynamically controlled conditions at higher temperature. In THF/HMPA at −70°C, competitive 1,2 and 1,4 additions take place in nearly all cases examined: when starting from a p -methoxy-substituted reagent, both reactions are kinetically controlled, while with unsubstituted and m -chloro-substituted reagents, kinetic and/or thermodynamic control of 1,4 addition occurs. The application of this reaction to synthesis of γ-cyanoaldehydes is considered.

Trimethylsilyl enol ethers formed by an imino Diels-Alder reaction: Mechanistic implications

Abstract Diastereomeric silyl enol ethers 3 and 4a–c have been isolated starting from 1 and 2a–c in the presence of AlCl 3 , implying a concerted process. The structures of 3c and 4c were assigned by single crystal X-ray crystallography.

Effet de solvant sur support solide:régiosélectivité de l'alkylation des énolates de l'acétylacétate d'éthyle par le sulfate d'éthyle en présence de “hmpt solide”

Abstract The reaction of Li, Na, K enolates of ethylaceto acetate with diethylsulfate in THF at room temperature gives 60–70% O-alkylation when performed in the presence of one molar equivalent of solid HMPA. Without HMPA, in the same conditions, Li enolate docs not react, Na enolate only gives C-alkylation while K enolate leads to 90% C-alkylation, the reactions being quite slower in the two latter cases. The effects of one molar equivalent of solid and liquid HMPA are compared: for the K enolate the reaction is faster and the degree of O-alkylation higher with solid HMPA; practically no difference is seen for Na enolate, while the reverse is observed with the Li enolate. The cooperative effect of the polymer should thus only work for a sufficiently large cation, as the Li enolate is fixed on the solid HMPA in a larger amount than the K enolate. The study of this reaction is proposed to test the efficiency of other “solid solvents” interacting strongly with cations.

Selectivite de la reduction de l'androsten-4 dione-3,17 et de la progesterone par divers borohydrures: role de l'assistance electrophile par le cation ou un solvant hydroxyle

Abstract The reduction of Δ 4 -androsten-3, 17 dione 1 and of progesterone 2 by n Bu 4 NBH 4 is highly chemioselective: in THF only the a -enone moiety is reduced, the saturated C 17 or C 20 keto group being kept unchanged. When TMEDA is added, saturated alcohols are obtained, without any allylic alcohol when the reaction goes to completion. However this reduction is poorly stereoselective as 70:30 mixtures of A/B cis and trans ring junction compounds are obtained. In MeOH, the saturated keto group is more than 90% selectively reduced. However, the reduction of 1 and 2 by LiBH 4 and Zn(BH 4 ) 2 is poorly chemioselective. These results are interpreted in terms of competition between electrophilic assistance and steric effects.