Sulfoxides, allylic optically active

Sulfoxides are optically active at the S atom. The natural ( + ) isomers are better substrates than the (—) isomers or the racemic mixture 18, 42). Among saturated alkyl groups, the garlic enzyme is most active on the ethyl derivative 18) while the onion enzyme prefers the propyl derivative (42). The rate differences (at substrate concentration = 0.02M) are caused solely by differences in 42). However, the natural alkenyl sulfoxides (allyl in garlic, 1-propenyl in onion) are the best substrates for the respective enzymes 18,43), and the onion enzyme... 

An asymmetric synthesis of estrone begins with an asymmetric Michael addition of lithium enolate (178) to the scalemic sulfoxide (179). Direct treatment of the cmde Michael adduct with y /i7-chloroperbenzoic acid to oxidize the sulfoxide to a sulfone, followed by reductive removal of the bromine affords (180, X = a and PH R = H) in over 90% yield. Similarly to the conversion of (175) to (176), base-catalyzed epimerization of (180) produces an 85% isolated yield of (181, X = /5H R = H). C8 and C14 of (181) have the same relative and absolute stereochemistry as that of the naturally occurring steroids. Methylation of (181) provides (182). A (CH2)2CuLi-induced reductive cleavage of sulfone (182) followed by stereoselective alkylation of the resultant enolate with an allyl bromide yields (183). Ozonolysis of (183) produces (184) (wherein the aldehydric oxygen is by isopropyUdene) in 68% yield. Compound (184) is the optically active form of Ziegler s intermediate (176), and is converted to (+)-estrone in 6.3% overall yield and >95% enantiomeric excess (200). 

Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

Sulfoxides (R1—SO—R2), which are tricoordinate sulfur compounds, are chiral when R1 and R2 are different, and a-sulfmyl carbanions derived from optically active sulfoxides are known to retain the chirality. Therefore, these chiral carbanions usually give products which are rich in one diastereomer upon treatment with some prochiral reagents. Thus, optically active sulfoxides have been used as versatile reagents for asymmetric syntheses of many naturally occurring products116, since optically active a-sulfinyl carbanions can cause asymmetric induction in the C—C bond formation due to their close vicinity. In the following four subsections various reactions of a-sulfinyl carbanions are described (A) alkylation and acylation, (B) addition to unsaturated bonds such as C=0, C=N or C= N, (C) nucleophilic addition to a, /5-unsaturated sulfoxides, and (D) reactions of allylic sulfoxides. 

Demailly and coworkers195 found that the asymmetric induction increased markedly when optically active methyl pyridyl sulfoxide was treated with an aldehyde. They also synthesized (S)-chroman-2-carboxylaldehyde 152, which is the cyclic ring part of a-tocopherol, by aldol-type condensation of the optically active lithium salt of a,/3-unsaturated sulfoxide. Although the diastereomeric ratio of allylic alcohol 151 formed from lithium salt 149 and 150 was not determined, the reaction of 149 with salicylaldehyde gave the diastereomeric alcohol in a ratio of 28 72196. 

The observations of the interconversion of allylic sulfenates and sulfoxides made by Braverman and Stabinsky34-38 are confirmed by the work of Mislow and coworkers44-47 who approached the problem from a different angle, namely, enhanced racemization of optically active allylic sulfoxides. 

In order to account for the unusually facile thermal racemization of optically active allyl p-tolyl sulfoxide (15 R = p-Tol) whose rate of racemization is orders of magnitude faster than that of alkyl aryl or diaryl sulfoxides as a result of a comparably drastically reduced AH (22kcalmol- ), Mislow and coworkers44 suggested a cyclic (intramolecular) mechanism in which the chiral sulfoxide is in mobile equilibrium with the corresponding achiral sulfenate (equation 10). 

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

The thermal racemization of optically active aryl allyl sulfoxides ArS(0)CHjCH=CH2 is orders of magnitude faster, and has a much lower activation energy, than that of aryl alkyl sulfoxides ArS(0)R (Bickart et ai, 1968). The reason is that the presence of the allyl group permits the sulfoxide to equilibrate with the isomeric, achiral sulfenate ester by a concerted, cyclic process (89) for whichis only about 20 kcal moM.The rates of racemiz-... 

Chiral allylic alcohols.1 Desulfuration of the (3-hydroxy sulfoxides 1 with Raney nickel (11, 292) proceeds with simultaneous reduction of the double bond, but can be effected selectively with lithium in ethylamine at - 78° to give optically active allylic alcohols (2). 

Since allyl sulfoxides may quite easily undergo racemization at the sulfur atom via a reversible [2,3] sigmatropic process, the configurationally more stable chiral allylic phosphine oxides were also investigated.201 Compounds (184) and (185), prepared as a 1 1 mixture from allylphosphonyl dichloride and (-)-ephedrine, were shown to add to cycloalkenones with reasonably high diastereoselectivities. Ozono-lysis of the initially formed 1,4-adducts affords the respective optically active ketoaldehydes (Scheme 67). With a / /-isopropyl-substituted derivative even higher selectivities (88-98% ee) could be obtained. 

A novel approach to the asymmetric synthesis of epoxides, allylic alcohols, a-amino ketones, and a-amino aldehydes from carbonyl compounds through a,/i-epoxy sulfoxides using the optically active p-tolylsulfmyl group to induce chirality./. Org. Chem. 1989, 54, 3130-3136. 

Asymmetric synthesis of a chroman. Solladie and Moine have effected an en-antiospecific synthesis of the chroman-2-carboxaldehyde 7, a key intermediate in the synthesis of a-tocopherol, from (R)-( +)-l. The phosphonate 2, derived from 1, undergoes a Wittig-Horner reaction with the dimethyl ketal of pyruvaldehyde to afford the optically active vinyl sulfoxide 3. Condensation of the aldehyde 4 with the lithio derivative of 3 affords, after silyl deprotection, the allylic alcohol 5 as the only diastereoisomer. This... 

Oxidation of -substituted allylic sulfides with 3-chloroperoxybenzoic acid or periodate usually yields S-epimeric sulfoxides, which can be directly subjected to the rearrangement to give optically active allyl alcohols. The enantiomeric excess is determined by the preference of the transoid transition state over the cisoid transition state. 

Synthesis of P-Keto Sulfoxides. Optically active p-keto sulfoxides are very useful building blocks (eq 4) because they can be stereoselectively reduced to afford either diastereomer of the corresponding p-hydroxy sulfoxide under appropriate conditions (Diisobutylaluminum Hydride or Zinc ChloridefDlBALf and thus give access to a wide variety of compounds chiral carbinols by desulfurization with Raney Nickel or LithiumJethyhmme ini the case of allylic alcohols epoxides via cyclization of the derived sulfonium salt butenolides by alkylation of the hydroxy sulfoxide 1,2-diols via a Pummerer rearrangement followed by reduction of the intermediate. ... 

Hua has used the products of Pauson-Khand cycloadditions for syntheses of optically active pental-enene and racemic pentalenolactone E methyl ester. The racemic ketone in the first case was converted to the necessary optically active intermediate by kinetic resolution via 1,4-addition of an optically active allyl sulfoxide anion. These represented the first synthesis of natural products containing the angularly fused triquinane skeleton from bicyclic Pauson-Khand products (equation 53 and Scheme 20). ... 

This 2,3-sigmatropic shift has been of substantial utility since Evans and Hoffmann realized that allyl alcohols can be obtained by intercepting the sulfenate with thiophilic agents. One possible way of preparing optically active allylic sulfoxides, which started to racemize even at 0 C was the isomerization of the corresponding vinylic sulfoxide followed by the sulfenate rearrangement in the presence of trimethyl phosphite (Scheme 51). ... 

Allylic and propargylic 3-keto sulfoxides could be reduced as well as saturated compounds. Optically active allylic 3-hydroxy sulfoxides present some specific interest because of the possible hydroxylation of the double bond leading to vicinal triols. The osmium tetroxide catalyzed hydroxylation reaction of the double bond in the presence of trimethylamine N-oxide is highly stereoselective the (/ ,/ )-3-hydroxy sulfoxide gave only one diastereoisomeric triol as a result of a cis hydroxylation of the double bond and a symbiotic effect of the two chiral centers in the asymmetric induction (the (S,/ )-isomer gave a lower de). 

Hoffmann has used an isomerization of readily available aryl vinyl sulfoxides, which can be obtained in optically active form, to study the possibility of generating optically active allyl alcohols by employing chirality transfer from sulfur to carbon. While this synthetic route (Scheme 18) to allylic alcohols generally works well and gives good yields, the optical yields which could be obtained are only satisfactory in some cases, e.g. (/ )-(Z)-sulfoxide (13) gave the (S)-(+)-octenol (14) with greater than 80% optical purity, whereas the (/ )-( 5-isomer (15) yielded only 29% of the (f )-(-)-enantiomer (16 Scheme 19). 

Besides the low optical yields of the reaction the known hazard of racemization and ( )/(Z)-isomeriza-tion of optically active allylic sulfoxides, which can only be avoided below 0 C, limits the synthetic utility of such a process. 

Allylic sulfoxides (181) and sulfenates (182) are related by a reversible reaction (equation 56). The equilibrium is shifted towards the sulfoxide. Due to the low barrier associated with this 2,3-shift optically active allylic sulfoxides can racemize at room temperature. Accordingly, the reaction of an alcohol (183) wift PhSCl via sulfenate (182) continues through the 2,3-rearrangement to the sulfoxide. Allylic sulfenates are very seldom isolable. When, conversely, an allylic sulfoxide (181) is heated in the presence of a thiophile (P(OMe)3, R NH, NaSR), the sulfenate (182) is removed from the equilibrium mixture by O—S bond cleavage. The ultimate reaction product obtained from an allylic sulfoxide, therefore, is an allylic alcohol (equation 56). 

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