SYNTHETIC EQUIVALENT GROUPS Cyclohexenone is reactive toward nucleophiles. It is often advantageous to combine the need for masking of a functional group with a change in the reactivity of the functionality in question. need for masking of a functional group change in the reactivity of the functionality The nucleophile that is required is not normally an accessible entity. The acyl anion, must be introduced in a masked form through suitable reagents
SYNTHETIC EQUIVALENT GROUPS Synthetic equivalent group a masked functionality used in place of an inaccessible species Often, the concept of "umpolung" is involved in devising synthetic equivalent groups. the reversal of the normal polarity of a functional group Umpolung • Acyl groups are normally electrophilic, but a synthetic operation may require the transfer of an acyl group as a nucleophile. • The acyl anion equivalent would then be an umpolung of the acyl group.
SYNTHETIC EQUIVALENT GROUPS Nucleophilic equivalents for the introduction of acyl group 1)O-protected cyanohydrins This sequence has been used to solve the problem of introducing an acetyl group at the b-position of cyclohexenone
SYNTHETIC EQUIVALENT GROUPS These reagents are capable of adding the a-alkoxyvinyl group to electrophilic centers. Nucleophilic equivalents for the introduction of acyl group 2)a-lithium allylethers 3)a-lithium vinylethers • Subsequent hydrolysis can generate the carbonyl group and complete the desired transformation.
SYNTHETIC EQUIVALENT GROUPS Nucleophilic equivalents for the introduction of acyl group Sulfur compounds have also proven to be useful as nucleophilic acyl equivalents. 3)1,3-dithianes Lithiation of the 1,3-dithiane ring provides a nucleophilic acyl equivalent. The litihio derivative is a reactive nucleophile toward alkyl halides and carbonyl compounds.
SYNTHETIC EQUIVALENT GROUPS Nucleophilic equivalents for the introduction of acyl group 5)ethylthiomethylthiosulphoxides In both the dithiane and alkylthiomethylsulfoxide systems, an umpolung is achieved on the basis of the carbanion-stabilizing ability of the sulfur substituents.
SYNTHETIC EQUIVALENT GROUPS Nucleophilic equivalents for the introduction of the propanal homoenolate Another group of synthetic equivalents which have been developed corresponds to the propanal "homoenolate" This is the umpolung equivalent of an important electrophile, the a,b-unsaturated aldehyde acrolein
SYNTHETIC EQUIVALENT GROUPS • In general, the reagents used for these transformations are reactive toward such electrophiles as alkyl halides and carbonyl compounds. • It should be noted that all deliver the aldehyde functionality in a masked form, such as an acetal or enol ether. The aldehyde must be liberated in a final step from the protected precursor. • Several of the reagents involve delocalized allylic anions. This gives rise to the possibility of electrophilic attack at either the a or g position of the allylic group. In most cases, the g attack, that is necessary for the anion to function as a propanal homoenolate, is dominant.
SYNTHETIC EQUIVALENT GROUPS a) b) c)
SYNTHETIC EQUIVALENT GROUPS d) e) f)
SYNTHETIC EQUIVALENT GROUPS Another level of the concept of synthetic equivalent groups is reached with dipolar species. These structures incorporate both electrophilic and nucleophilic centers. Such reagents might be incorporated into ring-forming schemes, because they have the ability, at least formally, of undergoing cycloaddition reactions. Among the real chemical species that have been developed along these lines are cyclopropylphosphonium salts.
SYNTHETIC EQUIVALENT GROUPS Some examples
SYNTHETIC EQUIVALENT GROUPS It should be recognized that there is no absolute difference between what is termed a "reagent" and a "synthetic equivalent group.“ • For example, we think of potassium cyanide as a reagent, but the cyanide ion is a nucleophilic equivalent of a carboxyl group. This reactivity is evident in the classical preparation of carboxylic acids from alkyl halides via nitrile intermediates. The general point is that synthetic analysis and planning should not be restricted to the specific functionalities that must appear in the target molecules. These groups can be incorporated as masked equivalents by methods that would not be possible for the functional group itself.