The stereodivergent synthesis of cis- and trans-2,6-disubstituted tetrahydropyrans (THPs) via sodium hexamethyldisilazide-promoted oxa-Michael cyclization of (E)-ζ-hydroxy α,β-unsaturated esters is presented. The cyclization affords the kinetically favored trans-THPs with high stereoselectivity (dr up to 93:7) at a low temperature (-78 °C), while the room-temperature reaction does not produce the thermodynamically preferred cis-THPs as major products and occurs with poor stereocontrol. The addition of tetramethylethylenediamine (TMEDA) significantly improves the stereochemical outcome of the room-temperature cyclization and allows attaining high cis-selectivity (dr up to 99:1). The remarkable effect of TMEDA indicates that the sodium cation plays an important role in controlling the stereoselectivity of the thermodynamically driven process, that is, complexation of the cation with the cyclization products results in diminished selectivity. DFT calculations support this conclusion, indicating a greater difference in Gibbs energies of sodium-free cis- and trans-enolates compared to the respective sodium chelate complexes. The synthetic utility of the method has been demonstrated by the formal syntheses of (+)-Neopeltolide and (-)-Diospongin B and the total synthesis of (-)-Diospongin A.