Alcohols with Additional Nucleophilic Groups

If the 7-substituent in the starting norbornenone has anti orientation with respect to the carbonyl group, the nucleophilic addition occurs from the exo face. However, transformation to the allylsilanes and stereospecific epoxidation lead to the required alcohol with the vinyl group endo, as demonstrated by the stereoselective synthesis of dihydronepetalactone 591071. 

Many of the most interesting and useful reactions of aldehydes and ketones involve trans formation of the initial product of nucleophilic addition to some other substance under the reaction conditions An example is the reaction of aldehydes with alcohols under con ditions of acid catalysis The expected product of nucleophilic addition of the alcohol to the carbonyl group is called a hemiacetal The product actually isolated however cor responds to reaction of one mole of the aldehyde with two moles of alcohol to give gem mal diethers known as acetals... 

Nucleophilic addition of an alcohol to the carbonyl group initially yields a hydroxy ether called a hemiacetal, analogous to the gem diol formed by addition of water. HcmiacetaJs are formed reversibly, with the equilibrium normally favoring the carbonyl compound. In the presence of acid, however, a further reaction occurs. Protonation of the -OH group, followed by an El-like loss of water, leads to an oxonium ion, R2C=OR+, which undergoes a second nucleophilic addition of alcohol to yield the acetal. The mechanism is shown in Figure 19.12. 

A urethane is typically prepared by nucleophilic addition reaction between an alcohol and an isocyanate (R—N = C=0), so a polyurethane is prepared by reaction between a cliol and a diisocyanate. The diol is usually a low-molecular-weight polymer (MW 1000 amu) with hydroxyl end-groups the diisocyanate is often toluene-2,4-diisocyanate. 

Figure 3.4 The synthesis of ibuprofen is initiated by a Friedel-Crafts acylation of an aUcyl-substituted benzene ring. The resulting ketone is then reduced to an alcohol with sodium boro-hydride. The alcohol functionality then undergoes a functional group interchange by conversion to a bromide. In turn, this permits the introduction of an additional carbon atom in the form of a nitrile introduced via an 8, 2 nucleophilic displacement. This is then hydrolyzed to give the target molecule.

Acetylide (RC=CNa) and alkynide (RC=CMgX and RC=CLi) are good nucleophiles. They react with carhonyl group to from alkoxide, which under acidic work-up gives alcohol. The addition of acelylides and alkynides produces similar alcohols to organometallic reagents. 

Some strategies used for the preparation of support-bound thiols are listed in Table 8.1. Oxidative thiolation of lithiated polystyrene has been used to prepare polymeric thiophenol (Entry 1, Table 8.1). Polystyrene functionalized with 2-mercaptoethyl groups has been prepared by radical addition of thioacetic acid to cross-linked vinyl-polystyrene followed by hydrolysis of the intermediate thiol ester (Entry 2, Table 8.1). A more controllable introduction of thiol groups, suitable also for the selective transformation of support-bound substrates, is based on nucleophilic substitution with thiourea or potassium thioacetate. The resulting isothiouronium salts and thiol acetates can be saponified, preferably under reductive conditions, to yield thiols (Table 8.1). Thiol acetates have been saponified on insoluble supports with mercaptoethanol [1], propylamine [2], lithium aluminum hydride [3], sodium or lithium borohydride, alcoholates, or hydrochloric acid (Table 8.1). 

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