Synthesis of 1′-Homologated-3′-Modified Adenosine Derivatives through Asymmetric Intramolecular S N 2′ Alkylation Using an Evans Chiral Auxiliary

1'-Homologated-3'-modified adenosine derivatives were designed and synthesized as peroxisome proliferator-activated receptor γ (PPARγ) modulators. The stereoselective synthesis of cis-tetrahydrofuran was achieved through an Evans oxazolidinone-based methodology, generating two stereogenic centers via an asymmetric intramolecular SN2' alkylation. Density functional theory calculations confirmed the reason behind the cis-selectivity, highlighting the role of noncovalent interactions between the oxazolidinone and allylic functionality that stabilize the key transition state structure leading to the major product.