Substitutions potassium ferf-butoxide

Imperial Chemical Industries (ICI) chemists " prepared a novel series of spirocyclic 2,4-oxazolidinediones 243 derived from 7-substituted isatins (Scheme 6.54). The key intermediate a-acyloxy amides 242 were readily prepared from 241 in three steps. Base-catalyzed cyclization of 242 then afforded the target compounds that were reported to be potent inhibitors of aldose reductase. Pfizer chemists approached 5-substituted isatin spirocyclic analogues 243 via a-hydroxy esters 244 that were converted to the corresponding a-carbamyloxy esters 245 in good yield using chlorosulfonyl isocyanate. Cyclization of 245 with potassium ferf-butoxide then produced 243 in acceptable yield (Scheme 6.54 Table 6.10, Fig. 6.20). 

Cyclization of 3-substituted 2-chloromethyl-4-oxo-l,2,3,4-tetrahydro-quinazolines (7) with potassium ferf-butoxide in /m-butanol afforded 8 [66TL2609 74CPB601,74JAP (K) 7431687,74JAP (K) 7431697]. Blocking N-3 of the quinazoline nucleus is necessary to direct the cyclization towards AM. 

If, however, the base itself is a crowded one, such as potassium ferf-butoxide, even primary alkyl halides undergo elimination rather than substitution ... 

Dehydrohalogenation of (bromomethyl)cyclohexane with potassium ferf-butoxide, a sterically hindered and strong base, would give the desired alkene as the major product. The substitution derived from SN2 displacement of the halide by the alkoxide might also be obtained as a minor product. 

The transition state for the reaction resembles the product more than the reactant and so the factors that stabilise the product also stabilise the transition state and make that particular route more likely. However, the opposite preference is found when potassium ferf-butoxide is used as base, and the less substituted alkene is favoured. 

Enamines derived from cyclohexanone and / - and a-tetralones react with chloro-(phenyl)carbene [generated from dichloro(phenyl)methane and potassium ferf-butoxide] to give either 1-chloro-l-phenyl-substituted cyclopropanes, or other products.140-143 The type of products formed depends on the structure of the amine moiety in the starting enamines (Table 7). 

Dibromocarbene undergoes addition to the more substituted (more nucleophilic) double bond of unconjugated di- and polyenes di- and polyadducts may also be obtained, particularly using the bromoform/base/phase-transfer catalyst method. For the preparation of monoadducts, using an excess of diene possessing equivalent double bonds, bromoform and base/phase-transfer catalyst or potassium ferf-butoxide are recommended. The examples l,34 235 3,35,36 and 435 are typical. 

Poly( y-mercapto acids). y-Thiobutyrolactone did not polymerize in bulk at 155°C with potassium ferf-butoxide as initiator (17). This is probably because of an unfavorable monomer-polymer equilibrium, resulting in a low ceiling temperature. It might be possible to overcome these difficulties by using lower polymerization temperatures or high pressure techniques, or both. A similar behavior has been reported for y-butyrolactone (18), which could be polymerized at elevated temperatures at 20,000 atm. It is likely that substituted y-thiolactones are even more difficult to polymerize. 

Poly(e-mercapto acids). In a series of papers, Overberger and Weise (17, 20, 21) reported the polymerization of e-thiocaprolactone (XXIV) and of some substituted analogs (see Table VI). XXIV could be polymerized in bulk or tetrahydrofuran solution, using bases such as butyllithium, potassium ferf-butoxide, or sodium as initiators. A1C13 as initiator gave a crosslinked product. Linear poly(e-thiocaprolactone) is crystalline and soluble in chlorinated hydrocarbons. 

Phosphonodithioic anhydride, 152-153 Phosphoryl chloride, 285 Phthalimide, 126 Piperidine, 259 substituted, 245 Piperylene, 8, 53 trani-Piperylene, 130, 137, 152 Potassium ferf-butoxide, 25 Praziquantel, 62 Prodigiosin, 348... 

In extension of our silver(l)-mediated synthesis of pyrroles, we have developed a catalytic version which could be realized by using a tosyl function as acceptor at the nitrogen atom. Thus, cyclization of A-tosyl-substituted homopropargylamines 12 to A -pyrrolines 13 has been achieved with catalytic amounts of the silver(l) salt. Aromatization by subsequent elimination of p-toluenesulfinic acid on treatment with potassium ferf-butoxide as base afforded the pyrroles 14 (Scheme 4) [31]. 

While allyl and glycidyl ethers are converted into a mixture of oxetane and oxepine products with xec-butyllithium, Mordini and co-workers reported that allyl, benzyl, and propargyl epoxy ethers can be regioselectively converted into 2-vinyl, 2-phenyl, or 2-aIkynyl-3-(hydroxyalkyl) oxetanes upon treatment with either Schlosser s base or other mixed metal bases. Some of the best results were obtained with the LDA/potassium ferf-butoxide mixture (LIDAKOR, ref 194). While rearrangement of propargylic or benzylic epoxide ethers formed exclusively the four-membered oxetanes, rearrangements of allyl oxiranyl ethers show a selectivity for cyclization to the seven-membered ring. Trialkylsilyl-substituted epoxide allyl ethers also show a preference for the oxepine, and mixtures are obtained as the size of the silyl substituents is increased (Scheme 17). 

On the basis of this palladium-mediated Michael addition cyclization process, a novel two-step synthetic entry into functionalized furan derivatives 67 has also been devised (Scheme 28). Substitution of benzylidene (or alkyli-dene) malonates for their ethoxymethylene analog (65) as activating olefins gave rise to the formation of the corresponding 2-ethoxy-4-arylidene tetrahy-drofurans 66. An in situ addition of potassium ferf-butoxide induced a decar-boxylative elimination reaction which was followed by an isomerization of the exocychc double bond. The entire process successively involved a conjugate addition, a palladium-catalyzed cycHzation-coupling reaction, a base-induced eliminative decarboxylation, and finally, a double bond isomerization (73). 

Azines and diazines are more difficult to deprotonate. Pyridine itself undergoes monometalation using n-butyllithium/potassium ferf-butoxide in tetrahydrofuran at — 100°C, with a regioselectivity related to the reaction conditions. Polar media favor the 4-metalated product, while in apolar solvents the 2-substituted product is formed preferentially (1). ... 

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