We reasoned that the electronegative fluorine atom may activate these substrates sufficiently to enable reduction to occur. A range of (E)-and (Z)-fluoroenoates were synthesized via a Horner-Wadsworth-Emmons reaction-(E) or TiCl4 mediated aldol condensation-(Z) and subjected to the reaction (Figure ). Authentic samples of reaction products were synthesized via a one-pot substitution/Krapcho decarboxylation. Whilst aryl (E)-enoates were accepted by the enzyme, the conversion was lower than with (E)-enones. The enzymes were most active towards electron poor enoates (4b, 98% yield) compared to electron rich enoates (4c, 55% yield). Both methyl (4a-c) and ethyl (4d) esters were accepted. In all cases the stereocontrol was excellent. However, (E)-alkylenoate (3e) and all tested (Z)-fluoroenoates showed no conversions. This was in line with the ketone results above, where a more sterically demanding ketone substituent (Et), comparable in size to OMe/OEt, led to low reactivity of the (Z)-isomer. This enzyme selectivity is especially useful when preparing the (E)-enoates via a Horner-Wadsworth-Emmons reaction. The resultant mixture of (E)and (Z)-enoates can be used in the ERED reaction without the need for prior separation with no decrease in the enantiopurity of the product. The reaction was amenable to biocatalytic preparative scale reactions (20-130 mg) giving an isolated yield of 89% of (S)-2a from (Z)-1a; 86% of (R)-2a from (E)-1a and 92% of (R)-2j from (E)-1j. Authentic reference standards of (R)-4a and (R)-2j were synthesized in order to accurately assign the absolute stereochemistry of the products (correlated by chiral HPLC) from the biocatalytic reactions. Experimental procedures and discussion of the assignments can be found in the Supporting Information. Docking studies were conducted to rationalize the high reactivities and excellent stereoselectivities observed with NCR. Using the reported X-ray crystallographic data for NCR (PBD database (4A3U)26 and substrates (E)-1a and (E)-3a and also (Z)-1a and (Z)-3a as ligands, in silico molecular docking was carried out using AutoDock Vina (v.1.2.0). 27 As indicated (Figure ) the ligands were orientated in the catalytic pocket of NCR with the carbonyl group complexed to His172 (3.69-4.41 Å, Van der Waal interaction) and Asn175 (2.91-3.17 Å, H-bond). Hydride transfer occurs from the reduced flavin to the β-C of the ligands while the α-C is reported to be protonated by Tyr177. The EREDs readily ac-cepted (E)-1a, (E)-3a, and (Z)-1a as substrates, while (Z)-3a was not accepted at all. This can be attributed to the different orientations of the substrates in the catalytic pocket (Figure ). Substrates (E/Z)-1a and (E)-3a can adopt productive conformations with hydride addition and then protonation in a trans-fashion to the alkene (Figure ). However, for substrate (Z)-3a, docked conformations are not productive as they would require hydride delivery and subsequent protonation to occur from the same face of the alkene (Figure ). In conclusion, a novel approach to enantioenriched sp 3 fluorides has been developed, via the bioreduction of α-fluoroenones and α-fluoroenoates. Notably, this provides access to a diverse array of functionalized chiral fluorinated compounds in good to excellent yields and stereoselectivities.