Cyclobutyl tosylates

B. Cyalobutyl toaylate. A 500-mL, three-necked, round-bottomed flask fitted with a stirrer and a thermometer is charged with 200 mL of pyridine (Note 5) and 32.3 g (0.448 mol) of cyclobutanol. The solution is stirred and chilled to 0°C, and then 89.8 g (0.471 mol) of p-toluenesulfonyl chloride (Note 5) is added in portions over a 20-min period. The reaction mixture is allowed to warm to room temperature and is stirred for 16 hr. The mixture is recooled to 0°C, and poured into 260 mL of concentrated hydrochloric acid in 800 mL of ice water. The mixture is extracted with three 300-mL portions of ether and the combined ethereal extracts are dried over anhydrous magnesium sulfate. The drying agent is removed by filtration and the filtrate is concentrated on a rotary evaporator. The residue 1s held under high vacuum (0.03 mm) at room temperature for 3 hr to give 93.3 g (92%) of cyclobutyl tosylate as a pale yellow oil (Note 7). 

Cyclobutyl tosylate Cyclobutanol, p-toluenesulfonate (8) Cyclobutanol, 4-nethylbenzenesulforate (9) (10437-85-1)... 

Cyclic substrates. Cyclopropyl substrates are extremely resistant to nucleophilic attack.285 For example, cyclopropyl tosylate solvolyzes about 106 times more slowly than cyclobutyl tosylate in acetic acid at (WC.286 When such attack does take place, the result is generally not normal substitution (though exceptions are known,287 especially when an a stabilizing group such as aryl or alkoxy is present) but ring opening 288... 

Although under solvolytic conditions carbocations are formed only as short-lived (transient) species, it is of interest to discuss here some recent work involving substituted C4H7+ cations which are relevant to the general discussions in the review. Wiberg and coworkers have carried out extensive studies on solvolysis reactions involving 3-substituted cyclobutyl tosylates 12 (equation 18), and rationalized the observed products by ab initio molecular orbital calculations at the MP2/6-31G level46,47. 

They have postulated that the solvolysis of 3-substituted cyclobutyl tosylates 12 (X = Alkyl, Ar, Cl, OEt, SiR 3) proceeds through the initial formation of bicyclobutonium ion in the rate determining step, which rearranges stereospecifically to the cyclopropyl-... 

A set of rapidly equilibrating carbenium ions might account for the rearrangements and the label scrambling but this cannot be the correct explanation, for cyclopropylcarbinyl, cyclobutyl, and allylcarbinyl systems all solvolyze much more rapidly than would be expected from model compounds. Thus, for example, the rate of solvolysis of cyclopropylcarbinyl tosylate is 10 times that of the solvent-assisted solvolysis of isobutyl tosylate.77 Cyclobutyl tosylate solvolyzes 11 times... 

Hydrolysis of the model cyclobutyl tosylates (298-OTs) in the presence of sodium borohydride furnishes the squalene-like diene (295a, 34%) and its double isomer 303 (12%) as well as the same two dienols (39%) mentioned previously 380). The reaction of 298-OTs with pyridine in benzene at 70°, conditions conducive to formation of elimination products, provides symmetrical phytoene-like triene 296a (56%) and its positional isomer 304 (28%). These transformations of cyclobutyl tosylate 298-OTs mimic closely the later steps proposed in the biogenesis of squalene and phytoene from their respective cyclopropane predecessors. 

Coates, R. M., and W. H. Robinson Solvolysis of /ra/i5-2,2-Dimethyl-3-(2 -methyl-propenyl)-cyclobutyl Tosylate. Model Reactions Relevant to Squalene Biosynthesis. J. Amer. Chem. Soc. 94, 5920 (1972). 

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