18.5: Strategy For Alcohol Synthesis (Retrosynthetic Analysis)

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From the pattern outlined above, one can devise a synthesis for a primary, secondary, or tertiary alcohol by reversing the steps shown in the examples in the previous page. In other words, knowing the structure of the target molecule, one can reason backwards and arrive at the starting materials needed for the synthesis. This approach is called retrosynthetic analysis, and it is also highly emphasized in organic chemistry courses. An example will serve to illustrate this point.

PROBLEM: How can the following alcohol be synthesized from simpler starting materials?

SOLUTION: First, note that the alcohol is tertiary. Tertiary alcohols can be synthesized from carbon nucleophiles and ketones. Second, it is also an internal alkyne. This suggests that an alkynide ion can be used as the nucleophile that reacts with the ketone.

To arrive at the starting materials, first identify the carbon bearing the hydroxyl group. This is the electrophilic carbon in the ketone. Next, identify the sp-hybridized carbon bonded to the hydroxyl-bearing carbon. This is the nucleophilic carbon in the alkynide ion. This leads directly to the fragments that represent the starting materials.

The complete synthesis starting from a terminal alkyne could be written thus:

See problem 10-2 (p. 437 in your textbook) for a similar example using Grignard reagents as the carbon nucleophiles.