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Enantioselective Enzymatic Naphthoyl Ring Reduction
Author(s) -
Willistein Max,
Haas Julian,
Fuchs Jonathan,
Estelmann Sebastian,
Ferlaino Sascha,
Müller Michael,
Lüdeke Steffen,
Boll Matthias
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201802683
Subject(s) - chemistry , enantioselective synthesis , stereocenter , spectroscopy , circular dichroism , birch reduction , ring (chemistry) , stereochemistry , cationic polymerization , substrate (aquarium) , photochemistry , catalysis , organic chemistry , physics , quantum mechanics , oceanography , geology
Birch reductions of aromatic hydrocarbons by means of single‐electron‐transfer steps depend on alkali metals, ammonia, and cryogenic reaction conditions. In contrast, 2‐naphthoyl‐coenzyme A (2‐NCoA) and 5,6‐dihydro‐2‐NCoA (5,6‐DHNCoA) reductases catalyze two two‐electron reductions of the naphthoyl‐ring system to tetrahydronaphthoyl‐CoA at ambient temperature. Using a number of substrate analogues, we provide evidence for a Meisenheimer complex‐analogous intermediate during 2‐NCoA reduction, whereas the subsequent reduction of 5,6‐dihydro‐2‐NCoA is suggested to proceed via an unprecedented cationic transition state. Using vibrational circular dichroism (VCD) spectroscopy, we demonstrate that both enzymatic reductions are highly stereoselective in D 2 O, providing an enantioselective pathway to products inaccessible by Birch reduction. Moreover, we demonstrate the power of VCD spectroscopy to determine the absolute configuration of isotopically engendered alicyclic stereocenters.