Solvent Dependency in Stereoselective δ-Lactam Formation of Chiral α-Fluoromalonate Derivatives : Stereodivergent Synthesis of Heterocycles with Fluorine Containing Stereocenters Adjacent to Tertiary Stereocenters

• The discovery and investigation of solvent dependency in stereoselective intramolecular amidation of chiral 5-aminofunctionalized-2-fluoromalonate ester derivatives, which gives access to highly functionalized δ-lactams with a quaternary fluorine-containing stereocenter, is disclosed. Experimental work together with density functional theory calculations led to understanding of how to direct and switch the stereochemical outcome of the stereoselective δ-lactam formation. The merging of this solvent-dependent stereoselective switch with asymmetric catalysis and cascade reactions gives access to an unprecedented strategy for stereodivergent synthesis of all possible stereoisomers of fluorine-containing stereocenters adjacent to tertiary stereocenters of a wide range of heterocyclic compounds with 95->99% ee in one-pot. It is also useful for application in total synthesis of fluorine-containing pharmaceuticals.

Ämnesord

NATURVETENSKAP  -- Kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences (hsv//eng)

NATURVETENSKAP  -- Kemi -- Organisk kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Organic Chemistry (hsv//eng)

Nyckelord

Solvent dependency

Stereoselective intramolecular amidation

Fluorine-containing quaternary stereocenters

Stereodivergent synthesis

Heterocycles

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