T-butoxide

Cydopentane reagents used in synthesis are usually derived from cyclopentanone (R.A. Ellison, 1973). Classically they are made by base-catalyzed intramolecular aldol or ester condensations (see also p. 55). An important example is 2-methylcydopentane-l,3-dione. It is synthesized by intramolecular acylation of diethyl propionylsucdnate dianion followed by saponification and decarboxylation. This cyclization only worked with potassium t-butoxide in boiling xylene (R. Bucourt, 1965). Faster routes to this diketone start with succinic acid or its anhydride. A Friedel-Crafts acylation with 2-acetoxy-2-butene in nitrobenzene or with pro-pionyl chloride in nitromethane leads to acylated adducts, which are deacylated in aqueous acids (V.J. Grenda, 1967 L.E. Schick, 1969). A new promising route to substituted cyclopent-2-enones makes use of intermediate 5-nitro-l,3-diones (D. Seebach, 1977). 

Eithium t-Butoxide Product Bulletin and Eithium Methoxide Product Bulletin, Chemetad GmbH, Frankfurt, Germany. 

Potassium t-butoxide in t-butyl alcohol requires powerful electron-attracting substituents at C-4 to effect ring opening of pyrazoles but sodamide does not (Scheme 26) (B-76MI40402). As the key to the transformation is the generation of the anion, similar results were obtained by heating some pyrazole-3-carboxylic acids with quinoline. 

Under conditions similar to those already outlined, stable aziridin imine derivatives, e.g. (422) and (423), can be prepared in excellent yields (70-80%) by treating the appropriate a-bromoamidines (easily accessible from the amide precursor) with potassium t-butoxide in ether <70AG(E)38l). At low temperatures the elimination proceeds with high regio- and stereo-selectivity at -40 °C (421) yields predominantly (422). 

The low-pressure gas-phase dehydrohalogenation of iV-chloroazetidine (270) using potassium t-butoxide supported on silica gives the parent 1-azetine (2) in excellent yield (81JA468>. This can be trapped at -196 °C, but rapidly undergoes polymerization at room temperature cf. Section 5.09.4.2.2). The 2-phenyl analogue of (2) can be prepared via a similar route (71IZV893). 

Comparison of the data for methoxide with those for t-butoxide in Table 6.4 illustrates a second general trend Stronger bases favor formation of the less substituted alkene. " A stronger base leads to an increase in the carbanion character at the transition state and thus shifts the transition state in the Elcb direction. A linear correlation between the strength of the base and the difference in AG for the formation of 1-butene versus 2-butene has been established. Some of the data are given in Table 6.5. 

CHjBr with potassium t-butoxide in r-butyl alcohol... 

The reactions of the cis and irons isomers of 4-/-butylcyclohexyltrimethylammonium chloride with potassium t-butoxide in r-butanol have been compared. The cis isomer gives 90% 4-r-butylcyclohexane and 10% AyV-dimethyl-4-r-butylcyclohexylamine, while the irons isomer gives only the latter product in quantitative yield. Explain the different behavior of the two isomers. 

The stereochemistry of hydrogen-deuterium exchange at the chiral carbon in 2-phenylbutane shows a similar trend. When potassium t-butoxide is used as the base, the exchange occurs with retention of configuration in r-butanol, but racemization occurs in DMSO. The retention of configuration is visualized as occurring through an ion pair in which a solvent molecule coordinated to the metal ion acts as the proton donor... 

Oppenauer reaction is oxidation of secondary alcohols to ketones using aluminium t-butoxide... 

Timko and Cram were the first to prepare true crown ethers containing the furanyl subcyclic unit ° . Destructive distillation of sucrose yielded 2-hydroxymethyl-5-formyl-furan 7 in 41% yield. This could be reduced to the corresponding diol in 91% yield by treatment with sodium borohydride. Reaction of the diol with tetraethylene glycol dito-sylate, and potassium t-butoxide in THE solution afforded the crown in 36% yield. The approach is illustrated below as Eq. (3.26). 

The 17a-ethynyl compound (59) has been prepared in 88% yield from estr-4-ene-3,17-dione (58) and acetylene, at 2-3 atm pressure in tetrahydro-furan in the presence of potassium t-butoxide. Presumably the A-ring enone system is protected as the enolate anion during the course of the reaction. 

Ethynylation of the totally synthetic racemic 18-methyl-17-ketone (63) with acetylene and potassium t-butoxide in t-butanol-toluene or with alkali metal acetylide in liquid ammonia gives a low yield of rac-18-methyl-17a-ethynyl-3-methoxyestra-l,3,5(10)-trien-17/ -ol (64). 

The direct base-catalyzed alkylation of 3-keto steroids is generally not a very satisfactory method for the preparation of monoalkylated products. However, under optimum conditions (short reaction time with methyl iodide, a Modest excess of potassium t-butoxide in boiling t-butanol) modest yields of... 

Gemdialkylated steroids are obtained as the major product when the alkylation is carried out under forcing conditions. Thus a good yield of (3) is obtained on methylation of 5a-cholestan-3-one with a large excess of potassium t-butoxide and methyl iodide. " ... 

The Roussel group has described recently a novel method for the synthesis of 2,2-dimethyl-A" -3-keto steroids. Thus addition of potassium t-butoxide to a solution of 19-nortestosterone (25) in tetrahydrofuran containing methyl iodide and hexamethylphosphorous triamide at —70° affords the 2,2-dimethyl compound (26) in good yield.Methylation of A" -3-ketone by the classical conditions, namely addition of methyl iodide to a solution of the steroid and potassium /-butoxide, leads to the 4,4-dimethyl product. 

Extension of the above method to 3-methoxyestra-3,5(10)-dien-17-one 17-ethylene ketal (46) prepared by base-catalyzed isomerization of 3-methoxy-estra-2,5(10)-dien-17-one 17-ketal (42) with potassium t-butoxide in dimethyl sulfoxide gives the isomeric tropone A-homo-estra-l,4,5(10)-triene-3,17-dione... 

Base catalyzed pinacol rearrangement of vicinal m-glycol monotosylates is a simple and useful general method for preparing perhydroazulenes. Thus, treatment of cholestane-5a,6a-diol 6-tosylate (115a) with either one mole-equivalent of potassium t-butoxide in f-butanol at 25° or with calcium carbonate in dimethylformamide at 100° gives a quantitative yield of 10(5 6/5H)... 

A simple and direct approach to 10(5 4j H)<2Z)eo-5-lceto derivatives lacking functionality in ring A is the controlled pinacol rearrangement of vicinal cw-diols analogous to the process described in the previous section. An example is the reaction of cholestane-4a,5a-diol 4-tosylate (136) with 1 mole-equivalent of potassium t-butoxide or with dimethylforraamide-calcium carbonate at reflux which gives a quantitative yield of Q(5ApH)abeo-cholestan-5-one (137). ... 

A number of reaction variables or parameters have been examined. Catalyst solutions should not be prepared and stored since the resting catalyst is not stable to long term storage. However, the catalyst solution must be aged prior to the addition of allylic alcohol or TBHP. Diethyl tartrate and diisopropyl tartrate are the ligands of choice for most allylic alcohols. TBHP and cumene hydroperoxide are the most commonly used terminal oxidant and are both extremely effective. Methylene chloride is the solvent of choice and Ti(i-OPr)4 is the titanium precatalyst of choice. Titanium (IV) t-butoxide is recommended for those reactions in which the product epoxide is particularly sensitive to ring opening from alkoxide nucleophiles. ... 

If however a t-butoxide was used as base, only the thermodynamically favored S-alkene 9 was formed, suggesting a ElcB-mechanism in that case. It has... 

The a -halosulfone, required for the Ramberg-Backlund reaction, can for example be prepared from a sulfide by reaction with thionyl chloride (or with N-chlorosuccinimide) to give an a-chlorosulfide, followed by oxidation to the sulfone—e.g. using m-chloroperbenzoic acid. As base for the Ramberg-Backlund reaction have been used alkoxides—e.g. potassium t-butoxide in an etheral solvent, as well as aqueous alkali hydroxide. In the latter case the use of a phase-transfer catalyst may be of advantage. ... 

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