Chiral Non-racemic Bicyclic Diketopiperazines: A Common Precursor to Explore Diverse Asymmetric Reactions Jonathan R. Scheerer The College of William & Mary, Department of Chemistry, Williamsburg, VA 23187 Bicyclic diketopiperazine (DKP) bearing a configurationally stable aminal stereogenic center is an effective platform from which to explore selective bond formation. The illustrated DKP can engage in a domino reaction sequence involving aldol condensation, alkene isomerization, and intramolecular hetero-Diels-Alder cycloaddition to prepare [2.2.2]-diazabicyclic structures. Excellent diastereofacial control during the cycloaddition is enforced with a removable chiral aminal substituent. The reaction sequence rapidly generates molecular complexity and is competent with both enolizable and non-enolizable aldehyde substrates. O
Ph N
N MeO
H
CHO
O N
O
NaOMe MeOH, 65 °C
N MeO
H Ph
diketopiperazine azadiene O Ph Ph
H
aldol condensation
O
N N
O
OMe alkene isomerization
Both enolizable and non-enolizable aldehyde substrates are viable (8 examples)
O IMDA [4+2]
H
'one pot' 67% yield
N
O OMe N dr 95:5 X-ray structure
[2.2.2]-diazabicyclo structures
! =
