Quenching with carbon dioxide

The stereochemistry of the carboxylation of 4-substituted ( + )-(/ S)-fra ,v-1-(4-mcthylphcnyl-sulfinylmethyl)cyclohexane after metalation with methyllithium and quenching with carbon dioxide was reported64. The results listed in Table 1 show that the d.r. of around 75 25 under kinetic control changes to 25 75 under thermodynamic control. This is the result of the equilibration of the two diastereomeric metalated species. As shown by the experiment in hexamethylphosphoric Iriamide (IIMI A) (d.r. = 57 43 under kinetic control) an electrophilic assistance of the lithium cation to the electrophilic approach is probably involved. 

Two traditional methods have been used to Introduce a carboxyl substituent at C-5 of uracil. 0ns iasolves bromlnatlon at C-5, metalatlon via a lithium-halogen exchange, and finally quenching with carbon dioxide (32) to give the C-5 carboxylic acid. The... 

Pyridine V-oxides may be deprotonated to give ylides which react with electrophiles such as carbon dioxide and ketones. For example, 4-chloropyridine /V-oxide reacts with butyllithium at -65 °C followed by quenching with carbon dioxide to give 4-chloropyridine A -oxide 2-carboxylic acid in 49% yield. Quinuclidine yV-oxide can be deprotonated with r-butyllithium to give the anion which can be trai ied with deuterium oxide or benzaldehyde. ... 

Reaction of l-chloro-4,4-bis(chloromethyl)pentane with magnesium in diethyl ether, followed by quenching with carbon dioxide, gave 4-(l-methylcyclopropyl)butanoic acid in 68% yield. Cyclopropane derivatives with electron-withdrawing substituents 5 were prepared by elec-troreductive dechlorination of 2,4-dichlorobutanoic acid derivatives in dimethyl sulfoxide solution in the presence of tetraethylammonium 4-toluenesulfonate at ambient temperature (yields 51 -90%).The starting materials for compounds 5 can easily be obtained by copper (I)-catalyzed photochemical addition of dichloromethane to electron-deficient alkenes. Electrochemical reductive 1,3-debromination has also been achieved however, it is of little synthetic value (experimental details are described in ref 16, with yields ranging from 39 to 94%). meso- and dimethyl sulfoxide gave equal amounts of cis- and transA, 2-dimethylpropane. ... 

Triple bromination of A -TIPS-pyri ole (6) with NBS affords tribromopyrrole 12 (97%) [22], which can either be deprotected to afford the marine acorn worm metabolite 2,3,4-tribromoindole 13 [22,23] or lithiated selectively at C-2 to give, after quenching with carbon dioxide, pyrrole carboxylic acid 14 [24],... 

These workers expanded their carbolithiation chemistry to ortto-aminostibenes (e.g., 16) in the synthesis of C-3 functionalized indoles (Scheme 5) [14]. Thus, Uthiation of 16 in the presence of pentamethyldiethylenetriamine (PMDTA) gave 17 as the major species in equilibrium with the Z-isomer. The structure of 17 was established by an x-ray structure determination of the carboxylic acid obtained upon quenching with carbon dioxide. Exposure of 17 to DMF yielded 18 (equation 1), which upon reaction with ethanol/p-toluenesulfonic add, thionyl chloride, and allyl-trimethylsUane/BFj-EtjO gave 19-21, respectively [14]. 

SCHEME 2. Quenching with Carbon Dioxide or Ethylene Oxide... 

Lombardino ( teaches that a t-butylsulfonamide group directs lithiation to the ortho position for which the resultant anion can be quench with carbon dioxide. 

Benzene and substituted benzene, in the presence of n-BuLi/ f-BuOK, undergo site selective metal-hydrogen exchange (eq 1). Best results are obtained in THF at —75°C or —50°C. Upon quenching with carbon dioxide, the corresponding acids are obtained in good to excellent yield. ... 

The discovery of o/t o-lithiation chemistry dates back to the late 1930 s, when Gilman and Wittig independently reported the ort/zo-deprotonation of anisole with n-BuLi and quenching with carbon dioxide. The vast scope of DoM chemistry has recently been extensively reviewed. This section will focus mainly on highlights of o/t/zo-lithiation used in the pharmaceutical industry. 

Attempts at an enantioselective deprotonation of 11 with sec-BuLi/(—)-sparteine and subsequent quenching with carbon dioxide gave the corresponding (f )-ds-3-azabicyclo[3.1.0]-hexane-2-carbo3grlic acid in only 73% ee (Scheme 11.44). This result led to the synthesis of the racemic acids and resolution with two separate approaches, diasteromeric salt formation and chiral chromatography. 

---