Under these optimized conditions, the scope of the reduction of S-2-pyridyl thioesters to the corresponding aldehydes was explored. As summarized in Scheme 2, electron-neutral and electron-rich carboxylic acids gave the corresponding aldehydes in good-to-excellent yields. Substrates with reducible functionality such as an aryl or heteroaryl bromide or chloride were unaffected, as shown by formation of products 3, 6, 7, and 14. Carboxylic acids containing thiophene, benzodioxole, indole, pyrrole (products 9-13) were reduced in moderate-to-good yields. Unfortunately, acids present within electron-deficient heterocycles including pyridine, pyrazine, pyrimidine, etc. are seemingly not amenable to aldehyde formation. Moreover, the presence of electron-withdrawing groups such as CF3, nitro, nitrile, ester etc. on an aromatic ring, likewise, resulted in almost no conversion to the corresponding aldehydes, perhaps due to the slow reductive elimination of the presumed intermediate nickel complex. Related attempts at reductions of aliphatic carboxylic acids under the same aqueous micellar conditions afforded only traces of the desired aldehyde, the major product being the corresponding hydrocarbon, potentially formed via decarbonylation of a Ni-acyl intermediate. Although there are clearly limitations in terms of scope, those acids that do participate and form aldehydes can be further functionalized in a 2-step, 1-pot fashion, as illustrated by products shown in Scheme 3. Thus, thioester of 3-iodo benzoic acid was first subjected to a Suzuki reaction with the corresponding boronic acid, whereupon it was reduced in the same pot by our catalytic system to the corresponding aldehyde in moderate yields. Scheme 3. 2-step one-pot sequence to synthesize functionalized aldehydes Within the toolbox associated with micellar catalysis lies its enabling properties in the area of biocatalysis. Thus, just having this amphiphile present in a buffered aqueous medium can dramatically enhance the extent of substrate conversion, where the nanomicelles present serve to accommodate the water-insoluble products that otherwise can accrue, leading to enzymatic inhibition. 35a By minimizing this undesired phenomenon, greater levels of product formation allow for 1-pot chemoenzymatic sequences which include ketoreductases (KRED), 35a ene-reductases (ERED), 35b lipases, 35c and aminotransferases (ATA) 35d in the aqueous reaction media. The advantages from such sequences leading to both "pot" and "time" 37 economy, among others (e.g., minimizing waste creation) are the subject of recent reports and reviews. A 4-step, 1-pot sequence, therefore, was developed involving the reduction of a carboxylic acid. In this case, formation of the derived aldehyde provides an activating group, enhancing the facility associated with the oxidative addition step required for a Pd-catalyzed cross coupling, notwithstanding its eventual further reduction. The extent of this activation can be seen from the relative rates of the Suzuki-Miyaura couplings involving both the benzaldehyde and the benzyl alcohol (Scheme 4). Hence, initial reduction of S-(pyridin-2-yl)-4-bromobenzothioate (3a) led to 4-bromobenzaldehyde which, without isolation, readily participated in a Suzuki-Miyaura coupling using only 5000 ppm (0.5 mol %) of Pd(dtbpf)Cl2 to afford the biaryl intermediate. Introduction of sodium borohydride resulted in the corresponding primary alcohol. Subsequent adjustment of the reaction mixture to pH 6 followed by addition of Palatase 20000L provided the corresponding ester (20) in 65% overall yield over 4 steps (Scheme 5). Often used metrics that indicate the level of "greenness" associated with an organic reaction include recyclability, in this case of the aqueous reaction mixture, as well as calculation of an E Factor, as first described by Sheldon years ago. Following an initial reaction from 2a to 2 (Scheme 6), product recovery is readily accomplished by inflask extractions using minimal amounts of recyclable EtOAc. Reuse of the water remaining in the same vessel for two additional cycles leads to good results in terms of product formation, even when using a different substrate (5a to 5). However, due to salt buildup and precipitation, further recycling could not be carried out. The E Factors associated with this sequence of steps was 2.51 (when recyclable extraction solvent EtOAc is not considered as waste; see ESI for calculations) and 11.06 (considering EtOAc as waste; see ESI). Importantly, ICP-MS analysis of products 2 and 5 from the recycled aqueous medium showed low levels of residual metal: 13 ppm Ni (see ESI), after silica gel chromatography, which is below the FDA-allowed 22 ppm per day per dose. 41 Scheme 6. Recycling of the aqueous reaction medium and calculation of E Factors Next, we started investigating the reduction of carboxylic acids to alcohols. The first step in activating the carboxylic acid to a more reactive S-2-pyridyl thioester was carried out in the same way as before by di-2-pyridyl dithiocarbonate (DPDTC) (see ESI). The reduction to the corresponding alcohol was facilitated by taking this reaction mixture and subjecting it to sodium borohydride in a one-pot fashion. Our investigation began by examining the reduction of the model compound, 4-bromo benzoic acid 21a to 4-bromo benzyl alcohol 21 (see ESI) under aqueous micellar conditions using a 2 wt% TPGS-750-M solution. Although the reduction went smoothly in water with full conversion of the thioester, a tremendous amount of foaming was observed when sodium borohydride was added to the TPGS solution due to the evolution of H2 gas, which was difficult to control, even on a small scale. As a result, we switched to an aqueous solution of 2 wt% Coolade 42 which is a low foaming surfactant that was developed by Lee et. al. for running reactions that evolve gases. Using 1.1 equivalents of DPDTC to make the thioester and 4 equivalents of sodium borohydride to facilitate the reduction, several bases were screened as the longevity of sodium borohydride increases under basic conditions in water. We observed that Et3N, Hunig's base and 2,6-lutidine gave almost similar yields of the alcohol by NMR. Even though the reaction could be carried out under aqueous micellar conditions, the formation of unwanted side products, i.e., the hydrolysis of the thioester back to the carboxylic acid under basic conditions, could not be avoided. So, next up we screened a bunch of green solvents that could be comparable to water in greenness. Both 95% EtOH/H 2 O and absolute ethanol gave similar yields of the alcohol, whereas methanol and 2-propanol gave inferior results (see ESI). The reaction with methanol gave the corresponding methyl ester as the major side product as determined by crude NMR. 95% EtOH/H2O was selected as the solvent of choice as it is cheap and commercially available in large quantities and is also a biomass derived product. Decreasing the number of equivalents of NaBH4 from 4 to 1.5 considerably dropped the yield to 50% by NMR (see ESI). As a result, we decided to go with 3 equivalents of NaBH4.