Dedicated to Dr. Günther Ohloff on the occasion of his 75th birthday
Keywords: (S)-4,4,4-Trifluoro-3-hydroxybutanoic acid / 2-Trifluoromethyl-3-hydroxypropanoic acid (F 3 -Roche acid) / Chiral CF 3 -containing synthetic building blocks / Natural products / Cyclizations / Olfactory comparison
The natural products pyrenophorin (1a) and citronellol (2a), citronellol is the first application of an enantiopure F 3 -Roche acid (12) as a synthetic builiding block (see its derivatives in which CH 3 groups are replaced by CF 3 , were synthesized in enantiomerically pure form from simple four-carbon 17-23). An olfactory comparison of
with citronellol and ent-citronellol (Scheme 6) shows that the trifluorohydroxy acids (obtained by resolution). The cyclizations of analogous CH 3 and CF 3 seco acids (cf. 9) to fluorine derivative has a "very metallic, aggressive" character and lacks totally the "sweetness" of (R)-(+)-and give pyrenophorin derivatives require different methodologies; the F 6 derivative 10a could be obtained in (S)-(-)-2a. A number of generally useful, CF 3 -substituted electrophilic (iodides 4, 18, 37, tosylates 19, 33, aldehydes 5, only very poor yield; in contrast to pyrenophorin. Most surprisingly, F 6 -pyrenophorin (1d) has an extremely poor 29, 39) and nucleophilic (Li dithiane precursor of 5, Li compounds 20, 38) reagents are described for the first time. solubility in common organic solvents, and has essentially no antimicrobial activity (see Table 2). The synthesis of F 3 - [a] Laboratorium für Organische Chemie der Eidgenössischen thio-1,3-dithiane was then alkylated by this iodide and for-Technischen Hochschule, ETH-Zentrum, mylated in situ (DMF) to give the aldehyde 5. Olefination