Chiral Non-racemic Bicyclic Diketopiperazines: A Common

Bicyclic diketopiperazine (DKP) bearing a configurationally stable aminal stereogenic center is an effective platform from which to explore select...
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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

! =