Blocking Fluorine Substitution in Biotransformation of Nortricyclanyl N‐Phenylcarbamates with Beauveria bassiana

Abstract

The biotransformation of tricyclo[2.2.1.02,6]hept‐3‐yl N‐phenylcarbamate (8) by a standard procedure using Beauveria bassiana gave a 7:1 mixture of optically active exo,exo‐ and exo,endo‐5‐hydroxytricyclo[2.2.1.02,6]hept‐3‐yl N‐phenylcarbamates 15 and 16 in 19% isolated yield. No ring opening of the three‐membered ring was observed. Substitution with a fluorine atom at the 5‐endo‐ or 5‐exo‐position prevented hydroxylation of any alicyclic position of the molecules, p‐hydroxylation of the aromatic ring occurring to a small extent instead. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Synthesis of Fluorinated Cycloalkyl N‐Phenylcarbamates and Their Microbial Defluorination/Oxygenation by Beauveria bassiana

“…), the molecular ion (m/z ϭ 253) and a characteristic fragment of 4-hydroxyphenyl isocyanate (m/z ϭ 135) were found. In conclusion, in contrast to the results obtained in the cases of 5-endo-and 5-exo-fluoronortricyclan-3-yl N-phenylcarbamate, [4] investigation of the biotransformation of cis-4-fluorocyclohexyl N-phenylcarbamate showed that monofluorination of a potential hydroxylation position did not prevent attack at this position, but resulted almost exclusively in hydroxylation/dehydrofluorination. In this way ketone 16 was formed, and was subsequently reduced to form compounds 17 and 18.…”

“…Examples of such so-called blocking fluorination have been observed with other microorganisms [9Ϫ12] and in the biotransformation of 5-fluoro-nortricyclan-3-yl N-phenylcarbamates with B. bassiana. [4] In contrast, biotransformation of 4-cis-fluorocycloalkyl N-phenylcarbamates 9 and 15 resulted in hydroxylation of all positions that were also attacked in the corresponding parent compounds. Hydroxylation of the fluoromethine groups most probably produces geminal fluorohydrins, which are not stable and are subsequently dehydrofluorinated to give the corresponding ketones 16 or (Ϫ)-20, the corresponding main products of the microbial transformation.…”

“…[3] Some recent examples of such transformations are mentioned in reference. [4] Distance models for hydroxylations of chemically nonactivated hydrocarbon positions in substituted alicyclics such as amides or carbamates have been developed, [5] extended, [6] and modified. [7] Hydroxylations of flexible and rigid mono-or polycyclic N-phenylcarbamates by B. bassiana occurred at a preferred distance of about 5 Å between the hydrogen atom that was replaced and the oxygen atom of the carbamate function directly attached to the carbocyclic skeleton.…”

“…The nonfluorinated parent carbamate was hydroxylated selectively in the 5exo-position. [4] We would now like to present our results on biotransformations, with B. bassiana, of fluorinated cycloalkyl Nphenylcarbamates bearing a fluorine atom in the 4-position relative to an electron-rich docking group, or in other words at a carbon atom that was shown to be hydroxylated in the case of the nonfluorinated parent carbamates e.g. at a carbon atom that was shown to be hydroxylated in the case of the nonfluorinated parent carbamates.…”

Regio- and stereoselective synthesis of vicinal fluorohydrins

“…For instance the ring opening of norbornadiene monoepoxide, which is extremely acid labile and which rearranges very easily to endo-bicyclo[3.1.0]hex-2-ene-6-carbaldehyde, could be transformed to a 75:25 mixture of diastereomeric fluoronortricyclanols by treatment of the epoxide with Me 3 NÁ3HF, which is slightly more acidic compared with Et 3 NÁ3HF. In this case ring opening of the epoxide and the transannular p-participation occurred very easily by heating at 45 8C for 45 min (Scheme 36) [116].…”