Enol sulfonates reduction

Desulfuration a-alkylation of -keto sulfones. Reductive alkylation of sul-fones is routinely carried out by a-alkylation of the enolate followed by desulfuration (Al/Hg). It can also be effected in one pot by desulfuration with lithium in liquid ammonia, which generates an enolate that can be alkylated. The yield is markedly enhanced by conversion of the lithium enolate to an alkylstannyl enolate by addition of BusSnCl with HMPT as cosolvent. 

Graphite-potassium Support for reduction of ketones, alkylhalides, alkyl sulfonate esters formation of enolate anions reduction of transition metals Bergbreiter and Killough, 1978 and references therein... 

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. ... 

In further modifications of these norprogestins, reaction of norethindrone with acetic anhydride in the presence of p-toluene-sulfonic acid, followed by hydrolysis of the first-formed enol acetate, affords norethindrone acetate (41). This in turn affords, on reaction with excess cyclopentanol in the presence of phosphorus pentoxide, the 3-cyclopentyl enol ether (42) the progestational component of Riglovic . Reduction of norethindrone affords the 3,17-diol. The 33-hydroxy compound is the desired product since reactions at 3 do not show nearly the stereoselectivity of those at 17 by virtue of the relative lack of stereo-directing proximate substituents, the formation of the desired isomer is engendered by use of a bulky reducing agent, lithium aluminum-tri-t-butoxide. Acetylation of the 33,173-diol iffords ethynodiol diacetate, one of the most potent oral proves tins (44). ... 

Rossi and Bunnett64 studied the chemical reductive cleavage of diphenyl sulfoxide, diphenyl sulfone and methyl phenyl sulfone under the action of potassium metal in liquid ammonia in the presence of acetone. The enolate ion is used to trap phenyl radicals formed eventually during the process, in order to determine whether one or two electrons are required for the mechanism of cleavage (Scheme 7). In all the runs, phenyl anion is... 

It is also appropriate to recognize the role of enolates stabilized by an exocyclic carbonyl function in C-glycoside synthesis. The use of LN to achieve reductive cleavage of anomeric sulfones to provide access to an ester-stabilized enolate and, ultimately, 2-deoxy- -C-glycosides has already been illustrated in Scheme 11 (Sect. 2.1.1). 

In fact, the sensitive disubstituted alkene of 14 turned out to not be stable to the subsequent A1C1, coupling conditions, so the alkene and the secondary alcohol were protected together as the bromoether 15. Condensation of the derived enol ether 16 with the sulfone 2 in the presence of DTBMP (2,6-di-/-butyl-4-methylpyridine) then gave 17. Yamaguchi lactonization followed by regeneration of the alkene by zinc reduction completed the synthesis of 1. 

Takaki reports that ketone enolates add to dimethylstyryl sulfonium perchlorate (155) or methyl styryl sulfone (156) in a Robinson-type annulation sequence to afford the corresponding 3-hydroxythiadecalin (157) or 5-dioxide (158), respectively subsequent reductive desulfonation of (158) affords diene (159).131 However, additions to acceptor (155) suffer from competing cyclopropanation which is dependent on the electrophilicity of the carbonyl group and the ring size of the ketone (Scheme 61). As an aside, DeLucchi reports that l,l-bis(benzenesulfonyl)ethylene (160) adds to ketones at the more substituted a-carbon under neutral conditions in refluxing acetonitrile (equation 18).132... 

Dialkyl alkynes. A recently reported route to these substances involves reductive elimination of enol phosphates of /8-oxo sulfones with sodium amalgam in DMSO-THF at 0°. 

A study carried out by Kocienski and Lythgoe flrst demonstrated the trans selectivity of the Julia coupling process. The authors found the i uctive elimination could best be carried out with the acet-oxy or benzoyloxy sulfones. If the lithio sulfone derivative is used for addition to the carbonyl, the reaction can be worked up with acetic anhydride or benzoyl chloride to obtain the alkene precursor. In cases where enolization of the carbonyl is a complication, the magnesium derivative can frequently be used successfully. A modification of the reductive elimination was found to be most effective. Methanol, ethyl acetate/methanol or THF/methanol were the solvents of choice and a temperature of -20 C was effective at suppressing the undesired elimination of the acetoxy group to produce the vinyl sulfone. With these modifications of the original procedure, the ability of the reaction to produce dienes as well as rran.r-disubstituted alkenes was demonstrated, llie diastereoisomeric erythro- and threo-acetoxy sulfones could be separated and it was demonstrated that both isomers were converted to the rrans-alkene. It... 

Both the enol phosphate method, and the reduction of the keto sulfone to the p-hydroxy sulfone followed by reductive cleavage to produce ( )-alkenes, have been applied to the synthesis of brefeldin A. Gais and cowoikers added the sidfone (462) to the lactone (461), formed the enol phosphate and reduced with sodium and ammonia to the ( )-alkene (463), in a 65% overall yield (equation 107). ... 

Trost added the sulfone (465) to the ester (464), and reduced the ketone to the alcdiol. In this example the formation of the enol derivative of the keto sulfone failed. The hydroxy group was functionalized with acetic anhydride, and the reduction to the alkene (466) carried out with the standard sodium amalgam conditions in 54% overall yield, as shown in equation (108). 

A connective synthesis of alkynes inspired by the Julia alkenation was developed by Lythgoe and coworkers for the synthesis of la-hydroxy vitamin D3, as shown in Scheme 34. The P-keto sulfone (101) derived by condensation of the the metalated sulfone (99) with the ester (100) was converted to the enol phosphate (102), which on reductive elimination gave the enynene (103). 

Fuchs has used this reaction type for the construction of an 11-membered ring in the course of model studies for the [ll]cytochalasin synthesis. These cytostatic compounds, e.g. cytochalasin C (109), are metabolites of microorganisms. Reductive fragmentation of the benzenesulfonates (110 Scheme 37) produces the dienols (111). In contrast, both the sulfonates (112) on treatment with LDA afford the tricyclic ketones (113), the products of internal alkylation. Less than 1% of (111) is formed. In conclusion, the author points out that the enolate conformation (Scheme 37, in parentheses) appears to be all important in determining the reaction products of the four diastereoisomers (110) and (112). Whenever the enolate can easily assume a folded conformation, the tricyclic cyclobutane (113) will result. Models of the enolates of (110), where the intraannular fragmentation successfully occurs, show that the folded conformations are more strained than are the extended conformations. 

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