Synthesis of propionate motifs: diastereoselective tandem reactions involving anionic and free radical based processes.
Reported herein is a strategy employing a Mukaiyama reaction in tandem with a hydrogen transfer reaction for the elaboration of propionate motifs. The nature of the protecting groups on the chiral beta-alkoxy aldehyde and the type of Lewis acid used are varied to modulate the stereochemical outcome of the tandem reactions. The mode of complexation is thus controlled (monodentate or chelate) for the Mukaiyama reaction to give access to either syn or anti aldol products, precursors of the free radical reduction reaction. The endocyclic effect is subsequently capitalized upon to control the hydrogen transfer step so that the syn-reduced product may be achieved. Proceeding with excellent yield and diastereoselectivity, the synthetic sequence proposed gives access to syn-syn and syn-anti propionate motifs. Also considered is a complementary approach using a chelation-controlled Mukaiyama reaction in tandem with a free radical allylation reaction under the control of the endocyclic effect that leads to the anti-anti product.
Guindon
Y
Y
Institut de recherches cliniques de Montréal (IRCM), Bioorganic Chemistry Laboratory, 110 avenue des Pins Ouest, Montréal, Québec, Canada H2W 1R7. guindoy@ircm.qc.ca
Houde
K
K
Prévost
M
M
Cardinal-David
B
B
Landry
S R
SR
Daoust
B
B
Bencheqroun
M
M
Guérin
B
B