Alcohols with proximate alcoholic groups

The landmark report by Winstein et al. (Scheme 3.6) on the powerful accelerating and directing effect of a proximal hydroxyl group would become one of the most critical in the development of the Simmons-Smith cyclopropanation reactions [11]. A clear syw directing effect is observed, implying coordination of the reagent to the alcohol before methylene transfer. This characteristic served as the basis of subsequent developments for stereocontrolled reactions with many classes of chiral allylic cycloalkenols and indirectly for chiral auxiliaries and catalysts. A full understanding of this phenomenon would not only be informative, but it would have practical applications in the rationalization of asymmetric catalytic reactions. 

Fluorine can share three sets of lone-pair electrons with electron-deficient atoms intramo-lecularly or intermolecularly, in particular with a relatively acidic hydrogen bound to a heteroatom. In addition, as described in section 1.4, strongly electron-withdrawing per-fluoroalkyl groups increase the acidity of proximate functional groups such as alcohol, amine, amide, and carboxylic acid. 

Zm complex (45) provided a model for the Zm -activated serine of AP (see Scheme 10). An alkoxide group in (45b) attacked BNPP to give a phosphorylserine intermediate (46), which was susceptible to further hydrolysis by the intramolecular Zn -bound hydroxide in (46b) to give (47) (Scheme 33). For the first step, the alcohol group is deprotonated by the proximate Zn (p7 a = 7.5) to an alkoxide complex (45b), which was 125 times more effective as nucleophile to the phosphate substrate than was the Zn -activated water of the reference compound (34). For the subsequent step, the nucleophilic Zn species (46c) was generated with a pXa value of 9. This intramolecular hydrolysis is 45,000 times faster than the intermolecular hydrolysis of ethyl 4-nitro-phenyl phosphate (ENP) with (34b). These results imply an advantage of the intramolecular arrangement of two Zn ions in AP (as shown in Scheme 10) over mononuclear Zn hydrolases. Toward any mononuclear Zn phosphatase model, phosphomonoesters were not substrates, but instead were inhibitors, as shown by isolation of the stable complexes (43), (44), and (47). The tris(pyrazolyl)-hydroborate complexes such as (35) and (38) hydrolyze phosphodiesters to phosphomonoesters, which similarly bind to Zn to become inert to further hydrolysis. ... 

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