Initial screens explored the reduction of (Z)-3-fluoro-4-phenyl-3-buten-2-one (1a) and reactions were monitored by HPLC analysis. The highest activity was seen with NCR, which gave the complete conversion of 1a to the desired fluoroalkane ((S)-2a) with excellent stereocontrol (>95:5 er, chiral HPLC analysis, Figure ). A range of substrates were then screened against NCR, pQR1445 and pQR1907. The highest activity was seen with NCR in all but one case. The NCR ERED was found to accept a wide range of α-fluoroenones and reductions occurred with excellent yields and stereoselectivities with both (Z) and (E)-α-fluoroenones being accepted by the enzyme (Figure ). Interestingly the opposite stereochemistry was observed starting from the (Z)-alkene compared to when the (E)-alkene was used. Substrates with a range of β-substituents were accepted, yielding fluorides containing electron poor (2b, 2d) and electron rich (2c) aryl groups, a range of aryl substitution patterns (2e, 2f), a heteroaromatic group (2g) and alkyl groups (2h, 2i). While most products were obtained in high yield and selectivity, the substrates for obtaining the (R)-o-tolyl product ((R)-2e) and pyridyl products (2g) were less well accepted. For the preparation of (R)-2e a higher enzyme concentration was needed but the reaction could not be pushed to completion and low stereoselectivity was observed. Low conversions were seen for both (Z)-and (E)-pyridyl substrates (1g) using NCR (<50% at 80% v/v enzyme lysate concentration). Changing the enzyme to pQR1445 (20% enzyme lysate concentration) gave excellent yields and moderate to good selectivities (94%, (S)-2g: 9:91 er; (R)-2g: 7:1 er). When the ethyl ketone (1j) was subjected to the reaction conditions the (E)fluoroenone gave the corresponding fluoroalkane (R)-2j in 98% yield and 99:1 er, however, the (Z)fluoroenone was poorly accepted and we saw <5% conversion to (S)-2j. A phenyl ketone was well accepted, however, giving fluoride (S)-2k in excellent yield and enantiopurity from the Z-enone, though the corresponding E-enone could not be purified effectively. c Conversion; no starting material remaining by GC but both product and starting material are volatile. d 80% (v/v) enzyme lysate concentration. (c) Substrate Scope of Fluoroenoates -40% (v/v) enzyme lystate concentration; e from 8:1 (E:Z); f from 5:1 (E:Z); g from 13:1 (E:Z); where the SM was a mixture of isomers, yield is based upon the conversion of the E isomer to the product.