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A three-step synthesis of (2 Z ), (4 E )-polyenic acids 6 is described. Condensation of aldehydes 1 with potassium prenal enolate led to dihydropyranols 3 which were oxidized into dihydropyrones 5 , precursors of (2 Z) , (4 E )-polyenic acids 6 . The procedure was applied to a synthesis of 13- cis -retinoic acids from β-ionylidene acetaldehydes.

Functionalized dienol ethers 6 were obtained in one pot from hydroxyacetal 3, via hydroxydienol ether 1 and anion 5, when treating 3 with n-butyllithium. It was shown that the transient organometallic species 5 occured only when the electrophile was added.

Vinylic lithium reagents 1 and 2 could be obtained by the title procedure from their chloro precursors 5 and 6 instead of the less stable corresponding bromo derivatives 3 and 4 . Condensation with carbonyl compounds leads to interesting synthetic applications such as a two steps synthesis of retinal 13 from β-cyclocitral 10 .

Condensation of enol ether 6 with methyl vinyl ketone led easily to ketoaldehyde 7 whose cyclisation afforded the azaspiranic enone 8, a key intermediate for the synthesis of the title alkaloids.

γ-Amino α,β-unsaturated dimethyl acetals are direct precursors of (E)-1-methoxy-2-methylamino-1,3-butadiene and of the corresponding bis-dienes, which are useful partners in cycloadditions.

Chiral lithio enol ethers 1 obtained from corresponding Z-bromo enol ethers react with alkyliodides, acylchlorides, leading to new chiral enol ethers of controlled configuration 5–8.

2,2-Di(ethoxy)vinyllithium 2 generated from bromo ketene acetal 1 reacts with carbonyl compounds to give either β-hydroxy esters 5 or conjugated esters 6 or hydroxy ketene acetals 7 according to the work up.

γ-Functionalized α,β-unsaturated dimethyl acelals undergo a methanol δ-elimination upon basic treatment, leading to 1,4-disubstituted 1,3-dienes in good yields and, in several cases, with high stereocontrol of the newly formed double bonds.

Semiempirical and ab initio calculations on (di)allylic alcohols indicate that the efficiency of their acid-catalyzed condensation with dienol ethers depends on their protonation-dehydration energies.

β-Trimethylsilyl enol ethers 1 ( Z ) obtained from β-bromoenolethers 2 were condensed with aliphatic and aromatic aldehydes in the presence of a catalytic quantity of trimethylsilyl triflate leading to ethylenic aldehydes 3 ( E ) with good yields (79–90%).

Functionalized dienol thioethers reacts with 3 eq. of thiophenol at room temperature in presence of dioxygen to give directly corresponding ketene dithiacetals in high yields.

2, 6-Dimethyl-8-methoxy-1-lithio-octatetra-1, 3, 5, 7-ene 4 is prepared by bromine-lithium exchange from its readily accessible bromo precursor 8 . The lithio reagent 4 reacts with carbonyl compounds to give in one pot, after a mild acidic hydrolysis, the retinoid aldehydes 2 .

Bromination of enamines of prenal and crotonaldehyde yields the corresponding ω-bromoaldehydes via the simple hydrolysis of iminium salts. The carbonyl function of these aldehydes can be protected as acetals or dioxolane. The overall process can be realized in a one pot procedure. The dioxolane is the starting material of a phosphonate which allows,by condensation with β-ionylidenacetaldehyde a direct access to the retinal with a 27.5% overall yield from the enamine 2

Trans-acetalization of the methyl acetal of 3-methyl-4-(phenylthio)-but-2-enal 2a in acidic medium leads to the expected trans-acetals 2b–f or their γ-elimination products (i.e. 4-alkoxy-2-methyl-1-(phenylthio)buta-1,3-dienes 4 ), depending on the nature of the selected alcohol. Both types of compounds may be easily oxidized into the expected sulfoxides 6 . The menthyloxy and phenyl-8-menthyloxy sulfides 4b,c and sulfoxides 6b,c have been prepared.

The deconjugation of methyl α-bromocrotonate has been performed and leads to the deconjugated ester and a pentasubstituted cyclopropane. The configuration of the latter is described.

A γ-condensation of the enolate of prenal 1 is observed with aldehydes and α,β-unsaturated aldehydes. In this last case, a conjugate addition is obtained. Intermediate dihydropyrans 4 yield dienals 5 by hydrolysis.

Enantioselective protonation was applied on amide enolates 1a and 2a , derived from piperidine-2-carboxylic acid. High enantioselectivity was obtained with diamine (+)- 3 , as chiral source, and in presence of LiBr. Up to 95±1% ee for amide 1 and >99% for amide 2 were reached. Moreover, (S)- 1 and (R)- 1 were obtained with 89% and 93% ee using (+) and (−) ephedrine respectively.

The OSM (oxidation state modification) concept for the elaboration of new synthetic pathways is demonstrated for the synthesis of β-ionylidene acetaldehyde 11 and retinal 13. According to this new scheme, electrophilic addition to ω-heterosubstituted enol ethers 5 of the cationic species 9, generated from β-ionol led to aldehydic intermediates 10 which undergo easy elimination to β-ionylidene acetaldehyde 11. Similarly, retinal 13 was obtained from vinyl-β-ionol 14 and dienol ethers 12, via aldehydes 16.

As precursors of molecular wires, linear conjugated polyenes with protected hydroquinone terminal groups 1a–c have been obtained from gentisic aldehyde by condensation with 1-ethoxy-6-lithiohexa-1,3,5-triene 6, followed by reacting the resultant aldehydes 5 with the dianion of the bis-phosphonate 7.

The enolate of prenal 1 prepared from the corresponding silyl enol ether 2 or enol acetate 3 led to a γ-regiospecific reaction with polyunsaturated aldehydes 4 yielding dihydropyrans 5 leading after hydrolysis to polyenals 7 . This process allows the introduction of the isoprenyl skeleton. A synthesis of retinal. from β-ionylidenacetaldehyde is reported.

Resume The alkylation of o-silylated enolates of ketones by α-chloro, α-(phenylthio or arylthio) ketone 1 in the presence of lewis acids leads to thiosubstituted 1,4 diketones 4 with good yields.

Chiral lithium amides exert asymmetric induction in dehydrohalogenation reactions leading to axially dissymmetric compounds. Thus the deracemization of 4-tert-butyl-cyclohexylidene acetic acid 1 via the prochiral hydrochlorinated intermediate 2 is reported with e.e. as high as 82 %.

The conversion of racemic α-hydroxyketone into optically active α-hydroxyketone with e.e. as high as 80 % and in good yield is reported. This is accomplished by a low temperature enantioselective protonation of the enediol using (2R, 3R) O,O-dipivaloyltartaric acid.

Optically active monobenzoate of cis-2-cyclopenten-1,4-diol is obtained by enantioselective acylation of the meso diol by benzoylchloride in the presence of tertiary chiral amines.

α-Ketoaldehydes with protected ketogroup 2 or protected aldehydrogroup 3 are obtained by reaction of thiophenol or methanol with α-chloro-α-(phenylthio)aldehydes 7.

In the search for the factors controlling the enantioselective protonation of enolates of α-aminoacid derivatives, we report a new procedure allowing the use of various ligands of lithium, involving an amine exchange after the metalation step by LHMDS and prior to the asymmetric protonation by means of a chiral acid. The stereoselectivity of this last step was affected by the ligand exchange. In some cases, a higher, e.e. was observed compared to the LDA or LHMDS procedure.

Lucette DUEAMRL*et Jean-Christophe PLAQUEVENT Laboratoire de Chimie Organique de la Facultd des Sciences et des Techniques de Rouen 76130 Mont Saint Aignan, France (Received in prance 29 March 1977; received in UK for publication 20 MW 197'7) L'introduction enantioselective de l'hydrogene sous forme d'anion hydrure ou sous forme moleculaire a Bte realisee avec succes dans de nombreuses reactions (1). Par contre, l'introduction enantiosdlective du proton n'a et6 utilisee que recemment pour la production de substances chirales (2 a 5). Pour notre part, nous avons decrit la "deracemisation" (6, 5) de l'aldehyde la en hydrolysant ses dnamines 2a (Z et E) par des solutions aqueuses d'acides mandelique ou tartrique chiraux, avec des rendements optiques de 4 % a partir de 2aE et de 14 % 1 partir de 2aZ (5). $H5-~=CH-N~0 % acide chiral 9 3 9 la (2) Nous avons developpe nos premiers resultats dans deux directions : l'am6lioration des rendements optiques et la generalisation a d'autres structures carbonylees. Les enamines isomeres 2aE et 2aZ ont et& hydrolysees dans l'ether, en presence des diffdrents acides diacyltartriques 3(L) prepares selon (7). Les resultats resumes dans le tableau 1 mettent en evidence l'influence de l'isomkie geometrique de l'enamine et de l'acide chiral. Le sens de l'induction depend principalement de la structure Z ou E de l'enamine. Pour l'enamine &E, le meilleur rendement optique (p = 25 %) a et4 obtenu avec R = Q 0 et pour 2aZ avec R = tC4H9-CH2(p = 24,8 %I. CH3 Nous avons etendu nos observations a la deracemisation de deux autres compos6s carbonyles, la c&one lb et l'alddhyde a-chlore Ic, en hydrolysant leurs Bnamines 2b et 2c en presence de solutions d'acide dibensoyltartrique L(+) (tableau 2). L'action de la morpholine sur l'a-mdthylcyclohexanone lb conduit a un melange d'enamines isomeres tetrasubstituee 2b et trisubstituee, dans le rapport 40/52 (9). Nous avons mis au point

Optically active α-aminoesters are obtained by metalation of the corresponding Schiff bases by chiral lithium amide followed by protonation by an achiral or a chiral acid. 70 % e.e. can be obtained.

β-Bromoenamines 4 and α-bromoaldehydes 6 are synthesised from the ambident anions 3 generated from either α-bromoaldimines 1 or α,α-dibromoaldimines 2 .