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1,1-Diphenylethylene, 1,1-di-p-tolylethylene, 1,1-di-p-anisylethylene and 1,1-di(p-t-butylphenyl)- ethylene are converted in high yields (80- 90%) into the corresponding 3,3,6,6-tetraaryl-1,2-dioxans in the presence of oxygen and catalytic amounts of antimony(v) chloride in dichloromethane at -40 to -78 under irradiation from a tungsten lamp.

1,1?-Bicyclohexenyl and α-terpinene are converted into the corresponding cyclic peroxides in the presence of oxygen and Lewis acids in dichloromethane. In liquid sulphur dioxide under oxygen, the . major product from 1,1?-bicyclohexenyl in the presence of SnCl4, SbF5, and SbCl5, is the corresponding cyclic sulphone, whereas the cyclic peroxide is almost exclusively formed in this medium with MoCl5, WCl6 and VOCl3. Under the same conditions, α-terpinene is quantitatively oxygenated in a dark reaction, in the absence of added Lewis acids. In a 1 : 1 dichloromethane-sulphur dioxide medium, ergosteryl acetate requires irradiation for conversion into the corresponding peroxide. Mechanistic interpretations of these observations are presented.

Some qualitative observations on the catalytic activity of Lewis acids in converting ergosteryl acetate into its 5α,8α peroxide are presented. The peroxide has an inhibiting effect on the reaction, which is ascribed to complex formation between it and the Lewis acid catalyst. This complex formation is used to explain the dual thermal and photochemical activity displayed by FeCl3 and MoCl5. A mixed oxygenation experiment with ergosteryl and lumisteryl acetates indicates that singlet oxygen is not an intermediate in this reaction. A model for the reaction, involving formation of a diene cation radical within a charge-transfer complex, is advanced.

The cyclization of compounds obtained from ethyl dienol ether and dienyl pivalate derivatives of Hagemann's ester has been examined. The carbanions of methyl phenyl sulfone and methyl phenyl sulfoxide react with the methylated dienol ether (4) to give the β-keto sulfone (8) and sulfoxide (9), the former of which was converted into the oxabicyclo[4.3.0]non-1-en-3-one (16). The iodide (17) with potassium t-butoxide in t-butyl alcohol gave the octahydronaphthalenone (18). With lithium ethoxide in tetrahydrofuran the octahydronaphthalenedione (22) was obtained from the dienyl pivalate (24). Both reactions involve the generation and intramolecular cyclization of a dienolate produced by cleavage of the pivaloyl group in each of (17) and (24). The scope and limitations of these reactions are briefly discussed.

The conjugate addition of (E)-1-(pheny1thio)oct-2-enyllithium in tetrahydrofuran containing hexamethylphosphoric triamide to γ-crotonolactone (but-2-en-4-olide) followed by treatment of the resulting lactone enolate with either methyl 7-bromohept-5-ynoate or 7-bromohept-5-ynenitrile gave the corresponding enolate trapped products in yields of 50-55% from the octenyllithium reagent. Use of 7-iodohept-5-ynoate gave a slightly higher yield than the first electrophile. Treatment of the enolate with triphenyltin chloride prior to addition of the electrophiles resulted in approximately 5-10% enhancement of the yields of the products. The products obtained from the methyl 7-halohept-5-ynoates were converted into the 9-oxo-l0-oxaprostanoids through the corresponding sulfoxides and the allylically transposed alcohols by a standard sequence of reactions. In an attempt to convert the lactone ring of the enolate-trapped products into the fully carbocyclic nucleus of primary prostaglandins, the nucleophilic ring opening of the lactone nucleus with the lithiated carbanion derived from t-butyl methyl sulfone in the presence of N, N, N', N'- tetramethylethylenediamine was carried out. However, attempts to oxidize the resulting hemiacetals to the requisite diketone precursors of the carbocyclic prostaglandins were unsuccessful.

The lithiated carbanions of (E)- and (Z)-1-(phenylthio)oct-2-ene, (E)-1-(methylthio)oct-2-ene, S-[(E)-oct-2-enyl] N,N-dimethyl( thiocarbamate ), S-[(a-oct-2-enyl] N,N-dimethyl- ( thiocarbamate ), and (E)- and (Z)-1-(phenylsulfony1)oct-2-ene undergo conjugate addition to γ-crotonolactone (but-2-en-4-olide) in tetrahydrofuran at -70 to give as predominant products, syn and anti allylic sulfides, thiocarbamates and sulfones arising from reaction through C1 of the octenyl carbanions . Also formed are smaller amounts of syn and anti vinylic sulfides, thiocarbamates and sulfones arising by reaction through C3 of the octenyl carbanions. The carbanions of the octenyl sulfones give smaller amounts of the vinylic products than do the other carbanions. In the presence of hexamethylphosphoric triamide (hmpa), the relative amounts of the latter compounds are depressed in favour of the former. The diastereoselection of these reactions is significantly smaller than the corresponding reactions involving 4-t-butoxycyclopent-2-enone. The constitutions and stereostructures of all the products was established by analysis of 1H n.m.r. data and n.O.e. difference experiments conducted at 400 MHz. The enhancement of the amounts of the allylic at the expense of the vinylic compounds induced by the hmpa is tentatively ascribed to frontier molecular orbital effects, and suggests that the operation of chelation and charge control in the reactions of related allylic carbanions with carbonyl compounds is less important than is generally considered to be the case. The various factors which cause carbanions to undergo conjugate addition to α β-unsaturated carbonyl compounds and the role played by the hmpa in these reactions are critically discussed in terms of the model of Seyden-Penne and coworkers.

Reaction of 4-t-butoxycyclopent-2-enone with (E)-1-(pheny1thio)oct-2-enyllithium in tetrahydrofuran containing 1.5 equivalents of hexamethylphosphoric triamide at - 78 followed by treatment of the resulting enolate with one equivalent of triphenyltin chloride and then with methyl 7-iodohept-5-ynoate at - 20 gives the vicinally dialkylated cyclopentanone, methyl (a-9-oxo-1l-t-butoxy-13-(phenylthio)prost-14-en-5-ynoate, as a 1 : 1 mixture of diastereomers epimeric at C13, in 70-72% overall yields from the octenyllithium reagent. Stereoselective reduction of the C9 carbonyl, conversion of the sulfide into the allylically transposed alcohol, and removal of the t-butyl group by means of iron(III) chloride in acetic anhydride at 0 provides a triacetate which is converted into racemic methyl 5,6-didehydroprostaglandin F2a methyl ester as a 1 : 1 mixture of diastereomers epimeric at C15.

The carbanions of (E)- and (Z)-1-(pheny1thio)oct-2-ene, (E)-1-(methy1thio)- and 1-(t-butyl- thio )oct-2-ene, N,N-dimethyl S-[(E)-oct-2-enyllthiocarbamate and (E)-oct-2-enyl benzothiazole undergo conjugate addition to 4-t-butoxycyclopent-2-enone in the presence of hexamethyl - phosphoric triamide ( hmpa ) in tetrahydrofuran at -70 to give as predominant products diastereomeric mixtures of syn and anti allylic sulfides arising from reaction through C1 of the octenyl carbanions. Also formed in some cases are small amounts of diastereomeric mixtures of syn and anti vinylic sulfides arising from reaction through C3 of the octenyl carbanions. In the absence of the hmpa, carbonyl addition is the major reaction pathway of the carbanions of each of the (E)- and (Z)- octenyl thiocarbamates. The constitutions and stereostructures of all the products have been established through chemical shift and coupling constant correlations of their IH n.m.r. data obtained at 400 MHz. The relative proportions of the regioisomeric allylic and vinylic sulfides are dependent both upon the nature of the non-allylic substituent attached to the sulfur atom, and the geometry of the double bond in the starting octenyl sulfide. While there is no apparent connection between the electronic properties or sizes of the non-allylic substituent and the diastereomer ratios of the allylic and vinylic sulfides, it is noted that the (2)-(phenylthio) octene delivers an allylic sulfide mixture enriched in the syn isomer. It is concluded that the carbanions are configurationally stable at-70 and that the configurations of the vinylic sulfides reflect the configurations of the carbanions from which they are derived. It is also concluded that the reactions proceed under orbital control, as this best accounts for the formation of the vinylic sulfides and is in accord with the results of STO-3G calculations carried out on a series of sulfur-bearing allylic carbanions . The likely angle of attack of the carbanions on the enone system is briefly discussed in terms of a published model relating to the attack of a simple nucleophile on an electrophilic double bond.

(E)- and (Z)-1-(Pheny1thio)oct-2-ene, (E)-1-(methylthio)- and 1-(t-butylthio)-oct-2-ene, S-[(E-oct-2-enyl] N,N- dimethylthiocarbamate , S-[(E)-oct-2-enyl] N,N- dimethylthiocarbamate , (E)-(oct-2-enylthio) benzothiazole , and S-[(E)-oct-2-enyl] N,N,N',N'- tetramethylphosphorodi - amidothioate have been prepared by nucleophilic substitution reactions and [1,3]- and [3,3]-sigma- tropic shifts involving intermediates prepared from oct-1-en-3-ol and (E)- and (Z)-oct-2-en-1-ol.

Methyl 7-hydroxyhept-5-ynoate, methyl 7-bromo- and 7-iodo-hept-5-ynoate, 7-hydroxyhept-5- ynenitrile, 7-bromohept-5-ynenitrile, 7-hydroxyhept-5-ynoic acid and 7-bromohept-5-ynoic acid have been prepared from 2-(prop-2-yny1oxy)tetrahydro-2 H-pyran and 1-bromo-3-chloropropane or 1-bromo-4-chlorobutane.

Tributyldiiodophosphorane and diiodotriphenylphosphorane, prepared in situ from the corresponding phosphine and iodine, are generally able to convert primary and secondary alcohols into iodides at room temperature in diethyl ether or benzene containing two equivalents of hexamethylphosphoric triamide. Tertiary alcohols, as gauged by the lack of reactivity of t-butyl alcohol, are, however, inert to these iodinating agents. 6-Hydroxyhexanoic acid yields a mixture of 6-iodohexanoic acid and 7-heptanolide. The first reagent also promotes facile condensation of secondary and tertiary alcohols with carboxylic acids to form hindered esters in good yields. The phosphorane derived from tris-(dimethy1amino)phosphine and iodine, while less effective as an iodinating agent, rapidly converts 6-hydroxyhexanoic acid into 6-iodo-N,N-dimethylhexanamide, and hexanoic and benzoic acids into the corresponding N,N-dimethylamides in excellent yields at room temperature. Treatment of 3β- tosyloxycholest-5-ene with lithium iodide yields 3β-iodocholest-5-ene, and not 3α-iodocholest-5-ene, as previously reported.

The reactions of lithiated 1-(t-butylsulfinyl)prop-2-ene, 1-(t-butylsulfinyl)-3-methylbut-2-ene, 1-(t-butylsulfinyl)but-2-ene, 1-(phenylsulfinyl)but-2-ene and 2-methyl-1-(phenylsu1finyl)prop- 2-ene with methyl vinyl ketone, mesityl oxide and crotonaldehyde give largely carbonyl addition products arising from reaction through C1 or C3 of the allyl system. In the case of methyl crotonate, conjugate addition through C3 is observed. The initially formed diastereomers of the C1 adducts, allylic sulfoxides, are configurationally unstable. Only the lithiated 1-(t-butylsulfinyl)-3-methylbut-2-ene undergoes conjugate addition with methyl vinyl ketone to give an (E)-vinyl sulfoxide whose formation may involve the trans-decalyl transition state characteristic of the reactions of lithiated allylic sulfoxides with cyclic enones.

Lithiated 4-(t- butylsulfinyl)- and 4-(t-butylsulfonyl )-6-methylhept-2-ene, and [(E)-1-isobutylbut-2-enylldiphenylphosphine oxide, undergo conjugate addition with cyclopent-2-enone and 2-methylcyclopent-2-enone to deliver mixtures of diastereomers arising from reaction through C3 of the allyl system. The relative configuration of the major product obtained from the lithiated phosphine oxide and 2-methylcyclopent-2-enone has been determined by an X-ray crystallographic study. The proportions of diastereomers formed are rationalized in terms of carbanions which have a low barrier to rotation about the C1-C2 bond of the allyl system, and steric interactions prevailing in the trans-decalyl and related transition states experienced by the reactions. The reaction of the lithiated phosphine oxide with 2-methylcyclopent-2-enone has a diastereoselection useful for synthetic approaches towards vitamin D derivatives.

Treatment of the neutral cyclopentanone adducts derived from the conjugate addition of each of lithiated 3-methylbut-2-enyl phenyl sulfoxide, (E)- and (Z)-but-2-enyldiphenylphosphine oxide to cyclopentenone with potassium t-butoxide results in intramolecular conjugate addition of the enolate arising from deprotonation at C5 of the cyclopentanone with the vinyl sulfoxide or phosphine oxide in the side chain togenerate bicyclo[2.2.l]heptanones in good yields. The use of an excess of lithium diisopropylamide at low temperature on the other hand results in kinetic deprotonation of the vinylic sulfoxide or phosphine oxide, and intramolecular nucleophilic addition of the resulting vinylic anions to the carbonyl groups in the respective adducts to generate bicyclo[3.2.l]octanols in acceptable yields. Application of the latter reaction to the lactone adduct of lithiated 3-methylbut-2-enyl phenyl sulfoxide and crotonolactone results in ring opening of the lactone to give a 2-(phenylsulfinyl)cyclohex-2-enone.

The lithium enolates arising by aprotic conjugate addition of lithiated but-2-enyl sulfoxides and a phosphine oxide to cyclopent-2-enone react efficiently with methyl cyanoformate to give the corresponding methyl 5-oxocyclopentanecarboxylates in good yields. The sulfoxides are smoothly deoxygenated with tributylphosphine diiodide in ether at 0, and the resulting sulfides undergo intramolecular cyclization in the presence of tin(IV)chloride to give methyl oxobicyclo [3.3.0] octanecarboxylates , again in good to excellent yields. The cyclizations are highly stereoselective in that the syn- and anti-stereochemistries of the enolate trapped products obtained from (E)-and (Z)- sulfoxides are quantitatively reflected in the products obtained from the cyclization reactions.

β- Sulfonylacrylate phenyl and t-butyl thioesters , and β- sulfonylvinyl ketones have been prepared by oxidation of the corresponding β-aryl- and β-alkyl- thio compounds. In one case the β- sulfonylvinyl ketone was obtained from an epoxy sulfone . The β-aryl- and β-alkyl- thio compounds were obtained by chlorination- dehydrochlorination of saturated precursors. The reactions of 3-( phenylthio ) propionyl chloride with organocadmium and Grignard reagents were used to prepare some of the saturated precursors of the β- sulfonylvinyl ketones.

Whereas the oxygenation of 1-t-butylcyclohexa-1,3-diene (4) in the presence of catalytic amounts of trityl tetrafluoroborate in dichloromethane at -78° under irradiation from a tungsten lamp gives two dimeric epidioxides as major products, cholesta-2,4-diene (5) gives under the same conditions a monomeric endoperoxide. The structures of the dimeric epidioxides have been established by a combination of chemical degradation, high-field 1H n.m.r. and an X-ray crystallographic study on the diketone (12) derived from one of the epidioxides. A mechanism involving the generation of intermediate monomer and dimer cation radicals is used to account for the formation of the dimeric epidioxides. The dimer cation radicals are expected to be more reactive than the monomer cation radicals towards oxygen. The dimerization is assumed to take place when the diene (4) and its monomer cation radical are aligned so that one reactant lies above the other whereby π-orbital overlap between the rings is maximized; oxygen is constrained to attack the one exposed face of the allylic radical system in the dimer cation radical. This accounts for the unique stereochemistry of the epidioxide products. Crystal data for diketone (12): a 29.975(4), b 5.767(1), c 11.758(2)Ǻ, β 111.67(2)°; C2/c; Z4.

The preparation of ethyl 4-ethoxy-2-methylcyclohexa-1,3-diene-1-carboxyate, ethyl 4-isopropoxy- 2-methylcyclohexa-1,3-diene-1-carboxylate, t-butyl 4-isopropoxy-2-methylcyclohexa-1,3-diene-1- carboxylate, ethyl 4-(t-butylcarbonyloxy)-2-methylcyclohexa-1,3-diene-1-carboxylate, and t-butyI 4-(t-butylcarbonyloxy)-2-methylcyclohexa-1,3-diene-1-carboxylate from Hagemann's ester and its t-butyl analogue in the presence of diethyl or diisopropyl sulfates and sodium hydride in dimethyl sulfoxide, or pivaloyl chloride and N,N,N',N'-tetramethylethylenediamine in tetrahydrofuran is described. The foregoing dienol ethers and esters are smoothly deprotonated by lithium diisopropyl- amide in tetrahydrofuran at -78" to give the corresponding ester dienolates, which react regio- specifically with a number of electrophiles, either a or y to the alkoxycarbonyl group of the dienol ether or ester. A number of the products, which are generally obtained in good yields, have been hydrolysed to Hagemann's ester derivatives substituted exclusively at C1.

The preparation of t-butyl 2-(phenylthiomethyl)propenoate, t-butyl and methyl 3-(phenylthio)-2-(phenylthiomethyl)propenoate, the corresponding carboxylic acids, and 3-(phenylthio)-2-(phenyl- sulfinylmethyl)propenoate from 3-bromo-2-(bromomethyl)propionic acid is described.

A series of (methylthio)- and (methylseleno)-triphenylphosphonium salts and the analogous tributylphosphonium salts have been prepared by methylation of the corresponding tertiary phosphine sulfides and selenides. Details of their 1H, 13C and 31P n.m.r. spectra are given. Whereas the (methylthio)- and (methylseleno)-triphenylphosphonium salts undergo rapid decomposition in the presence of tertiary ammonium carboxylates or tertiary amines, the (methy1thio)- and (methylseleno)-tributylphosphonium salts convert such carboxylates into methanethiol and methaneselenol esters in acceptable yields. A tris(dimethylamino)(methylthio)phosphonium salt, on the other hand, converts benzoate into methyl benzoate in quantitative yield. Inferior yields of (methy1thio)- and (methylseleno)-alkanes are obtained from two primary alcohols and the tributylphosphonium salts.

1,3-Diphenylisobenzofuran is converted into o-dibenzoylbenzene (40-70%) by oxygen, either in dichloromethane at -78° in the presence of 1-2 equiv. of a variety of Lewis acids, or on silica gel at 20°, in the dark. Tetraphenylfuran is converted into (Z)-dibenzoylstilbene (55-65%) under the former conditions in the presence of 0.05 equiv. of I2 or SnI4 under irradiation from a tungsten lamp. The conversions, which correspond to a mono-oxygenation process, do not involve as intermediates the furan endoperoxides, which were independently generated from the furans by use of singlet oxygen. 2,5-Dimethylfuran and p-menthofuran do not react with oxygen in the presence of Lewis acids under the foregoing conditions. Tetraphenylcyclopentadiene is converted by oxygen into the corresponding endoperoxide (70-85%) in the presence of 0.05 equiv. of I2 and SnI4 or 0.1 equiv. of Ph3C+BF4- in dichloromethane at -78° under irradiation.

A series of reagents for the conversion of enones into dienones via allylpalladium compounds has been studied and mild conditions for dienone preparation are recommended.