Evans Aldol Reaction: Leading Question
Above you can see the reaction scheme for the reaction this site is centered around. This reaction is one step of several in the synthesis of lysergic acid reported in the paper referenced below. This site investigates the stereoselectivity that occurs in this step's reaction. Additionally, a variety of total syntheses have been reported for lysergic acid because of its unique skeleton, and this paper helped contribute to the effort of synthesizing it with greater yields.
Central Paper:
Umezaki, S.; Yokoshima, S.; Fukuyama, T. Org. Lett. 2013, 15 (16), 4230-4233.
By appending a chiral auxiliary (see Evans' acyl oxazolidinone for a great examples of these) to a carbonyl group, you can form an enolate and remove the auxiliary during an aldol reaction resulting in a product with high stereoselectivity. The product takes on the same stereochemistry as the auxiliary allowing you to control the stereochemistry of a C-C bond in an aldol reaction. The reason why this works can be explained using Cram’s rule which essentially just says that the stereocenter is formed based on the steric hindrance. The following example shows an Evans Asymmetric Aldol Reaction using this principle.
As you can see in the example above, the attack occurs on the side of the hydrogens in the Newman projection, as it is the least hindered side. This causes the stereoselectivity observed.
The papers below all referenced our paper regarding the stereoselectivity of the reaction we are studying. The example discussed above, relating to stereoselectivity in an asymmetric Evans aldol reaction, was derived from these references.
Frye, S. V.; Eliel, E. L. J. Am. Chem. Soc. 1988, 110 (2), 484-489.
Evans, D. A.; Takacs, J. M.; Mcgee, L. R.; Ennis, M. D.; Mathre, D. J.; Bartroli, J. Pure & Appi. Chem. 1981, 53 (6), 1109-1127.
Evans, D. A.; Sjogren, E. B.; Bartroli, J.; Dow, R. L. Tetrahedron Lett. 1986, 27 (41), 4957-4960.
