SolutionsThe synthon
Exercise 1
Classify the following synthons in Seebach's d/a notation: a) the carbon of an acylium ion; b) the α carbon of an enolate; c) the β carbon of methyl vinyl ketone as a Michael acceptor; d) an acyl anion.
a) a1; b) d2; c) a3; d) d1. The a1, d2 and a3 synthons have the natural polarity imposed by oxygen; d1 inverts it and needs an umpolung equivalent, such as a lithiated dithiane.
Exercise 2
Disconnect 1,3-diphenylpropan-1-one at the C2–C3 bond and write the two possible pairs of synthons. Which one corresponds to real reagents?
Pair 1: the acetophenone enolate (−CH2COPh, d2) and the benzyl cation (PhCH2+); equivalents: the lithium enolate of acetophenone (LDA) and benzyl bromide. Pair 2: the cation +CH2COPh (a2, inverted polarity) and the benzyl anion; equivalents: α-bromoacetophenone and a benzyl organocuprate, possible but less direct. The first is an enolate alkylation.