This manuscript demonstrates the synthesis of selective Lewis-acid sites in a metal organic framework (MOF) for glucose transformation to 5-hydroxymethylfurfural (HMF). These sites are synthesized via partial phosphate modification of zirconia-cluster nodes in MOF NU-1000, which titrates strong Lewis-acid sites that would lead to undesired side reactions. Our Mechanistic study using isotope tracer analysis and kinetic isotope effect measurements reveals that an isomerization dehydration mechanism mainly occurs, on the MOF catalyst, where fructose is an intermediate. This mechanism suggests that dilute concentrations are favorable in order to suppress undesired intermorecul condensation of glucose/fructose/HMT and maximize HMF yield. We demonstrate both high yield and selectivity of HMF formation of 64% with the MOF catalyst, at an initial glucose concentration of 1 mM in water/2-propanol. In stark contrast similar partial phosphate modification of a bulk zirconia yields a catalyst that exhibits poor HMF selectivity, while possessing nearly identical Bronsted acidity to the selective NU-1000-based catalyst.