Grignard reagents disconnections using

Where we have a choice, it is better to disconnect the longer chain to get back to simple starting materials more quickly, as with ester (23). Here the Grignard reagent was used " without catalyst. 

Example The substituted 1,4-diol (4) must surely be made by a method which uses the symmetry of the structure. Disconnection (a) would require Grignard reagent (5) whose OH group would have to be protected. Disconnection (b) gives hydroxy ester (6) and here no protection is necessary as the internal ester (lactone) (7) serves the purpose. 

Disconnection 3 shows that any alcohol may be disconnected at a bond next to the OH group. Isomeric alcohols 18 and 20 can both be made from acetone using perhaps a Grignard reagent 19 in the first case and available BuLi in the second. 

The same disconnection 41 can be used for carboxylic acids with CO2 as the electrophile for a Grignard reagent 40. Dry ice (solid CO2) is particularly convenient for these reactions. Switching polarity by FGI to the nitrile 42, the same disconnection now uses cyanide ion as the nucleophile but the same alkyl halide 39 that was used to make the Grignard reagent. Mechanistic considerations should decide between these alternatives. 

We saw symmetry put to good use at the end of the last chapter and it may well help if we can do two identical disconnections at once. The symmetrical tertiary alcohol 10 can be made from two molecules of a Grignard reagent 11 and one of ethyl acetate. Then back to the alcohol 12 by FGI and a disconnection at the branchpoint gives the starting materials. 

All of these disconnections relied on the reaction of a carbon electrophile with a nucleophilic functional group. The alternative, reaction of a carbon nucleophile (such as a Grignard reagent) with an electrophilic functional group, allows us to do C-C disconnections on alcohols, For example, this compound, which has a fragrance reminiscent of lilac, is a useful perfume for use in soap because (unlike many other perfumes that are aldehydes or ketones) it is stable to alkali. 

The Grignard reagent from (41) has been widely used in synthesis. We recognise a bromide and an acetal disconnecting the acetal reveals a j3-bromo aldehyde available by Michael addition of Br" to acrolein (42)... 

Disconnection of ketones gives the synthon (1), for which we have previously used an ester, and a Grignard reagent. However, this approach is doomed from the start (see Chapter 10) as the ketone is formed in the presence of the Grignard reagent and is more reactive than the ester. Alcohols arc formed. 

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