AbstractVan der Waals complexes formed between chiral molecules in the isolated gas phase were studied by combining supersonic expansion techniques with laser spectroscopy. The weakly bound diastereoisomers formed between a chiral secondary alcohol, butan‐2‐ol, and a chiral aromatic derivative such as 2‐naphthyl‐1‐ethanol or 1‐phenylethanol used as a resolving agent were discriminated on the basis of the spectral shifts of the UV S0‐S1 transition of the chromophore. Ground‐state depletion spectroscopy (hole burning) has shown that, while only one structure was detected for the 1‐phenylethanol/butan‐2‐ol homochiral complex, the heterochiral complex is trapped in the jet under two different conformations. Two isomers have also been shown for each diastereoisomeric pair of the 2‐naphthyl‐1‐ethanol/butan‐2‐ol complexes. Using a semiempirical potential model, these isomeric forms were related to calculated structures which exhibit a folded or extended geometry depending on the solvent conformation (anti or gauche). The relative binding energy of the complexes involving R‐1‐phenylethanol and R‐ or S‐butan‐2‐ol were obtained from fragmentation threshold measurements following two‐color photoionization. Comparison of the diastereoisomers exhibiting a similar spectral signature shows that the homochiral pair is more stable than the heterochiral one by about 0.7 kcal/mol. The fragmentation threshold has been shown to depend on the jet‐cooled isomer and this result addresses the role of conformational control in enantioselective interactions. Chirality 13:715–721, 2001. © 2001 Wiley‐Liss, Inc.