Asymmetric synthesis of beta-amino-gamma-substituted-gamma-butyrolactones: double diastereoselective conjugate addition of homochiral lithium amides to homochiral alpha,beta-unsaturated esters.
Chiral alpha,beta-unsaturated esters, containing a single, gamma-stereogenic centre, show modest levels of substrate control upon conjugate addition of lithium dibenzylamide. Double diastereoselective conjugate additions of homochiral lithium N-benzyl-N-(alpha-methylbenzyl)amide to the homochiral alpha,beta-unsaturated esters display "matching" and "mismatching" effects. In each case, however, these additions proceed under the dominant stereocontrol of the lithium amide to give the corresponding beta-amino esters in high de. A remarkable reversal in stereoselectivity is noted by changing the ester functionality to an oxazolidinone. Subsequent O-deprotection and cyclisation of the resultant beta-amino adducts gives access to the corresponding beta-amino-gamma-substituted-gamma-butyrolactones in good yield and high de.
Department of Organic Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK. steve.davies@chem.ox.ac.uk.
Thaïs
T
Cailleau
Jason W B
JW
Cooke
Stephen G
SG
Davies
Kenneth B
KB
Ling
Alan
A
Naylor
Rebecca L
RL
Nicholson
Paul D
PD
Price
Paul M
PM
Roberts
Angela J
AJ
Russell
Andrew D
AD
Smith
James E
JE
Thomson
D015107:4-Butyrolactone / Q000138:chemical synthesis* / Q000737:chemistry; D000577:Amides / Q000737:chemistry*; D000598:Amino Acids, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D003500:Cyclization; D004952:Esters / Q000737:chemistry*; D018020:Lithium Compounds / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D013237:Stereoisomerism
D000577:Amides; D000598:Amino Acids, Cyclic; D004952:Esters; D018020:Lithium Compounds; D015107:4-Butyrolactone