Sulfonates, allylic reduction

LAH-CuCh used in moderate to large excess desulfurizes sulfides and dithioketals in good to very good yields (55-87%), but with allyl sulfides, migration of the double bond occurs. Finally vinyl phenyl sulfones are reductively cleaved in good yields (65%) without reduction of C=-C bonds even by an excess of reagent. ... 

Isomerization of allylic sulfones and reduction of conjugated double bonds (Eq. 62), are possible disadvantages of the use of Mg as an electron-transfer agent.117 The occurrence of Julia olefination of 1,2-disulfone derivatives is another important drawback when performing reductive desulfonylation on these kinds of substrates (Eq. 63).118... 

The Pd-catalyzed, LiHBEt3-mediated reductive desulfonylation of allylic sulfones is also used in the ligand-controlled stereoselective synthesis of dienes191 where it is possible to control the geometry of the diene by a proper selection of the palladium ligand as shown by the distribution of products 1 and 2 (Eq. 115). The method described herein is also applicable to the so-called integrated chemical processes , which allow the preparation of a wide variety of alkenes by combining alkylation of allylic sulfones and reductive desulfonylation in one pot.192,193... 

Amine oxides, sulfoxides, and selenoxides all undergo the [2,3] sigmatropic rearrangement. The equilibrium between allyl sulfoxides and allyl sulfenates lies on the side of the sulfoxide, but the equilibrium can be pushed toward the sulfonate by reduction of its O—S bond. 

This Pd-catalyzed LiHBEts reduction is applicable to integrated chanical processes (ICPs), which allows integration of alkylation of allylic sulfones and reductive desulfony-lation under mild basic conditions in one pot to prepare various olefins. ... 

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). 

The 2,2 -bis(phenylthiomethyl) dispiroketal (dispoke) derivative is cleaved by oxidation to the sulfone, followed by treatment with LiN(TMS)2. The related bromo and iodo derivatives are cleaved reductively with LDBB (lithium 4,4 -di- -butylbiphenylide) or by elimination with the P4- -butylphosphazene base and acid hydrolysis of the enol ether. The 2,2-diphenyl dispiroketal is cleaved with FeCl3 (CH2CI2, rt, overnight)." The dimethyl dispiroketal is cleaved with TFA, and the allyl derivative is cleaved by ozonolysis followed by elimination. ... 

The reductive elimination of a variety of )3-substituted sulfones for the preparation of di-and tri-substituted olefins (e.g. 75 to 76) and the use of allyl sulfones as synthetic equivalents of the allyl dianion CH=CH—CHj , has prompted considerable interest in the [1,3]rearrangements of allylic sulfones ". Kocienski has thus reported that while epoxidation of allylic sulfone 74 with MCPBA in CH2CI2 at room temperature afforded the expected product 75, epoxidation in the presence of two equivalents of NaHCOj afforded the isomeric j ,y-epoxysulfone 77. Similar results were obtained with other a-mono- or di-substituted sulfones. On the other hand, the reaction of y-substituted allylic sulfones results in the isomerization of the double bond, only. The following addition-elimination free radical chain mechanism has been suggested (equations 45, 46). In a closely related and simultaneously published investigation, Whitham and coworkers reported the 1,3-rearrangement of a number of acyclic and cyclic allylic p-tolyl sulfones on treatment with either benzoyl peroxide in CCI4 under reflux or with... 

Water-soluble transition-metal complexes have been used recently for transfer hydrogenolysis of halocarbons. Paetzold and Oehme [110] have realized the reductive dehaiogenation of allyl or benzyl halides in the presence of [(phosphine) 2PdCl2] complexes with sulfonated phosphines as ligands (e.g., Ph2P(CH2)3S03K) by... 

The desired products were obtained in satisfactory to excellent yields by using only 1.2 equivalents of the allylsulfones with primary, secondary and tertiary alkyl radicals. Many different types of allylic sulfones bearing an ester group, a sulfonyl group, and a bromine atom react equally well (Scheme 46). The whole transformation represents formally a reductive allylation or hy-droallylation of alkenes. 

A more recent synthesis of 197 [365] is shown in Fig. 9. Enders introduced the stereogenic centre of (S)-lactic acid into the crucial position 10 in 197. The vinylsulfone B, readily available from lactic acid, was transformed into the planar chiral phenylsulfonyl-substituted (q3-allyl)tetracarbonyliron(+l) tetra-fluoroborate C showing (IR,2S,3 )-configuration. Addition of allyltrimethyl silane yielded the vinyl sulfone D which was hydrogenated to E. Alkylation with the dioxolane-derivative of l-bromoheptan-6-one (readily available from 6-bro-mohexanoic acid) afforded F. Finally, reductive removal of the sulfonyl group and deprotection of the carbonyl group furnished 197. A similar approach was used for the synthesis of 198 [366]. 

A further eight steps were required to convert the cyclopentanone 52 into the sulfone 59 that was deprotonated and treated with an allylic bromide (60) to afford the alkylated sulfone 61 (Scheme 7). The sulfone moiety and the benzyl ether protecting group were reductively removed in a one-pot procedure to afford a mono-protected diol (62). 

The sulfone moiety was reductively removed and the TBS ether was cleaved chemoselectively in the presence of a TPS ether to afford a primary alcohol (Scheme 13). The alcohol was transformed into the corresponding bromide that served as alkylating agent for the deprotonated ethyl 2-(di-ethylphosphono)propionate. Bromination and phosphonate alkylation were performed in a one-pot procedure [33]. The TPS protecting group was removed and the alcohol was then oxidized to afford the aldehyde 68 [42]. An intramolecular HWE reaction under Masamune-Roush conditions provided a macrocycle as a mixture of double bond isomers [43]. The ElZ isomers were separated after the reduction of the a, -unsaturated ester to the allylic alcohol 84. Deprotection of the tertiary alcohol and protection of the prima-... 

See also page 47, Section 93 and page 49, Section 9.4, for reduction of sulfur-containing derivatives of alcohols and phenols and page 229, Section 4, for reduction of allylic sulfonates and sulfones with double bond transposition. 

The at complex from DIB AH and butyllithium is a selective reducing agent.16 It is used tor the 1,2-reduction of acyclic and cyclic enones. Esters and lactones are reduced at room temperature to alcohols, and at -78 C to alcohols and aldehydes. Acid chlorides are rapidly reduced with excess reagent at -78 C to alcohols, but a mixture of alcohols, aldehydes, and acid chlorides results from use of an equimolar amount of reagent at -78 C. Acid anhydrides are reduced at -78 C to alcohols and carboxylic acids. Carboxylic acids and both primary and secondary amides are inert at room temperature, whereas tertiary amides (as in the present case) are reduced between 0 C and room temperature to aldehydes. The at complex rapidly reduces primary alkyl, benzylic, and allylic bromides, while tertiary alkyl and aryl halides are inert. Epoxides are reduced exclusively to the more highly substituted alcohols. Disulfides lead to thiols, but both sulfoxides and sulfones are inert. Moreover, this at complex from DIBAH and butyllithium is able to reduce ketones selectively in the presence of esters. 

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