Sulfoxides lithiation

In the case of 2,2-disubstituted 1-alkenyl aryl sulfoxides, lithiation leads to an equilibrium between the E- and Z-isomeric species. 

Sulfones are similar in some ways even more acidifying, and with a powerful ability to coordinate, but less likely to be attacked at S. As with sulfoxides, lithiation a to S competes, and ortholithiation is useful only with sulfones lacking a-protons.141 After lithiation, the removal of sulfones can sometimes be accomplished by transition metal-catalysed reduction or substitution 144 143... 

However, addition of (+ )-(7 )-l-methyl-4-(mcthylsulfinyl)benzene, to aldehydes and ketones proceeds with low stereoselectivity. An improvement of the 3-syn diaslereoselectivity was found with the zinc reagent obtained by transmetalation of the lithiated sulfoxide with anhydrous zinc chloride38. An improvement of the stereoselectivity was also attained by exchange of the 4-methylphenyl substituent for a 2-methoxyphenyl or 2-pyridinyl substituent. Thus, the introduction of an additional complexing site into the aromatic part of the sulfoxide reagent enhances the stereoselectivity35. 

The lithiated sulfoxide was transmetalated with zinc chloride. 

Addition of BuLi to a 0.3 M solution of chloromethyl phenyl sulfoxide in THF at — 78 "C yields an immediate bright-yellow solution containing the lithio derivative which is stable for at least 2 h at —78 rC. Decomposition occurs rapidly above —20 C with the solution becoming turbid and the color changing to dark brown. Reaction of the lithiated solution of chloromethyl phenyl sulfoxide with cyclohexanone, acetone, or ben/ophenone for 10 min at —78 °C followed by 30 min at —20 rC yields one diastereomeT in 79, 75 and 68 % yields, respectively, after hydrolysis of the corresponding adducts. 

Lithiated racemic (E)- and (Z)-l-(/er/-butylsulfinyl)-2-methyl-2-butenes undergo addition to give predominantly anti-(E)-y- 1,4-addition products2. The sole difference between the major and minor adducts from the (Z)-sulfoxide with those from the (Z)-sulfoxide is in the relative configuration at sulfur. 

In contrast to allylic phosphine oxides, phosphonates, sulfones and sulfoxides, the chemistry of lithiated allylic sulfoximines has been less extensively developed25 27. The reaction of lithiated racemic A-phenyl-A -(4-rnethylphenyl)-S -(2-propenyl)sulfoximine with either 2-cy-clopentenone or 2-cyclohexenone gave a complicated mixture with 1,4-oc-ad ducts being slightly favored over the 1,4-7-adducts. The yields of these adducts were poor25. In contrast, lithiated racemic Ar-tert-butyldiphenylsilyl-5-phenyl-5,-(2-propenyl)sulfoximine gives mainly 1,4-y-ad-ducts on reaction with the same enones26. 

An a-fluorinated phosphinyl sulfoxide derivative, prepared as a mixture of diastereomers by the treatment of lithiated (a-fluoromethyl)diphenylphosphine oxide with menthyl p-toluenesulfinate, has been used for the preparation of enan-tiomerically pure 1-fluorovinyl and 1-fluoromethyl sulfoxides [76]. (E)-Diethyl ferf-butylsulfinylmethylphosphonate 117 has been prepared by the sulfinylation... 

Treatment of a-dichloromethyl phenyl sulfoxide with lithium diisopropylamide in THF gave monolithiated derivative 122, which upon further treatment with aldehyde afforded the )S-hydroxy-a-dichlorosulfoxide 123. Thermolysis of 123 gave dichloroketone 124, by extruding benzenesulfenic acid as shown below . Similarly, in the reaction of lithio-a-fluoromethyl phenyl sulfoxide and aldehyde, fluoromethyl ketone 126 was obtained, after thermolysis of the hydroxy intermediate 125. Diethylphosphorylmethyl methyl sulfoxide was shown by Miko/ajczyk and coworkers to be lithiated with n-BuLi to intermediate 127, which upon treatment with carbonyl compounds afforded the corresponding a, -unsaturated sulfoxides 128 in good yields. 

Nucleophilic addition of a-lithiated sulfoxides to a-PBN, followed by oxidation, gives (S-sulfinyl nitroxyl radicals (383) (Scheme 2.166) (621). 

Addition of Lithiated Sulfoxides and Sulfones Nucleophilic addition of lithiated methylaryl sulfoxides (384) to nitrones of various structures proceeds easily and in good yields (622). The reactions are applied to the synthesis of optically active a-substituted and a,a-disubstituted hydroxylamines, to secondary amines (623), and to enantioselective syntheses of alkaloids (624). The preferred approach to (+ )-euphococcinine is based on the use of homochiral 3-sullinyl nitrones (385) (Scheme 2.167). 

Acceptor-substituted allenes can be prepared from the corresponding propargyl precursors by prototropic isomerization (see Section 7.2.2). Conversely, such allenes can also be used to synthesize propargyl compounds. For example, treatment of the sulfoxides 417 with 1 equivalent of a lithiation reagent leads to the intermediates 418, which furnish propargyl sulfoxides 419 by hydrolysis (Scheme 7.55) [101]. If the electrophiles used are not protons but primary alkyl halides or carbonyl compounds, the products 420 or 421, respectively, are formed by C,C linkage. 

Phenyl sulfoxides 79 were lithiated in the presence of a catalytic amount of naphthalene or DTBB (5-8%) and an electrophile at —78 (naphthalene) or 0°C (DTBB) to room temperature, to give, after hydrolysis, the expected products 20 (Scheme 32). ... 

Numerous structures of a-lithiated amines, amides, carbamates as well as a-lithiated thioethers, sulfoxides, sulfones and sulfonamides have been determined. Although a slight... 

Metalated vinyl ethers are configurational stable up to —20°C in tetrahydrofuran. H-NMR measurements of 1-ethoxy-1-lithioethene TMEDA did not show any coalescence of the signals for the vinyl protons until the onset of decomposition. Thus, there is no evidence of inversion in this case . Similar configurational stability is displayed by a-lithiated thioethers in tetrahydrofuran no inversion occurs up to 0°C. On the contrary, deprotonated vinyl sulfoxides and sulfones are configurationally less stable . ... 

Direct lithiation of pyridazine 132 followed by trapping with chiral sulfinate esters produced chiral sulfoxides 133, analogous to the pyrimidine reaction covered in Section 6.2.2.2 <99JOC4512>. Queguiner and co-workers demonstrated that a second lithiation/trapping sequence can provide fully substimted pyridazines 134 with high diastereoselectivities. 

Lithiation and methylation of the equatorial sulfoxide, 4-/m-butyltetrahydro-2//-tluopyran 5-oxide led to a 10 90 mixture of axial and equatorial methylated sulfoxides. However, the corresponding axial sulfoxide afforded only the axial methylated sulfoxide 0-59,60. 

Table 3. Lithiation and Subsequent Alkylation of 1-Alkenyl Aryl Sulfoxides...

The stronger inductive effect of the sulfoxide group results in preferential a-deprotonation of (Z)-l-(ethylsulfmyl)-2-(ethylthio)ethene which leads to 1-substituted -products 6 via lithiated intermediate 2. Additionally small amounts of 2-substituted products 7 are formed via intermediate 3 due to /1-dcprotonation. Temperature dependent experiments demonstrate that a-lithi-ated Z-intermediate 2 is configurationally labile and is in equilibrium with the corresponding -intermediate which leads to products 5. 

Carboxylation of lithiated vinylic sulfoxides is also highly stereoselective, as shown by a one-pot experiment leading from optically pure (if)- -alkenyl aryl sulfoxides to optically pure methyl 2-arylsulfinyl-2-alkenoates without EjZ isomerization63. 

Disubstituted alkenyl sulfoxides can also be isomerized to the more stable geometric isomer of the lithiated species through chelation effects, and then reacted with electrophiles such as carbon dioxide. This is illustrated by, for example, the synthesis of optically active 2(5//)-fura-nones64. 

Chiral 2,2-disubstituted cyclobutanones have been obtained by asymmetric rearrangement of chiral sulfinyl- 177,178 and sulfanylcyclopropanes.179 Using readily available cyclopropyl 4-tolyl (/ )-sulfoxide (l),180 the requisite sulfinylcyclopropanes 3 and 3 were obtained by a sequence of lithiation, reaction with carboxylic acid esters and stereoselective addition of Grignard reagents to the ketones 2 thus formed.178 The corresponding sulfanylcyclopropanes 4 and 4 resulted from a sequence of protection, reduction and deprotection.179... 

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