We then moved our attention to automating the Matteson homologation, a reaction which allows the insertion of a methylene unit to the carbon chain of a boronic ester. Using phenethyl boronic acid pinacol ester (1) as the model substrate, the Matteson homologation using chloromethyllithium was targeted (Fig. ). In the laboratory, this reaction is performed in Et2O at -78 °C, with the carbenoid generated in situ from BrCH2Cl (3.0 equiv.) by slow addition of n-BuLi (2.5 equiv.). Maintaining the low temperature is crucial for minimising decomposition of the thermally unstable carbenoid, and slow addition of n-BuLi prevents its competitive reaction with 1 instead of BrCH2Cl. For a successful outcome on the automated platform, we found that a high shaking rate (1000 rpm) during the addition of n-BuLi was critical for uniform mixing, with lower rates resulting in poor yields or requiring a further excess of carbenoid (4 equiv.) for full conversion. Other modifications that were introduced to improve efficiency included (i) the reagents were added as stock solutions in anhydrous t-butyl methyl ether (TBME) instead of volatile and ignitionhazardous Et2O; and (ii) at the end of each liquid transfer, an extra 0.2 mL of TBME was added to the reaction vessel to prevent material loss in the lines (see Supplementary Materials). In order for the fully automated synthesis to accommodate all the steps of the synthetic procedure, the work-up of the reaction was also automated. In this case, using the solid-phase extraction module, the reaction mixture was transferred onto silica-loaded capped cartridges, followed by pressurization with inert gas. This allowed for automated silica-plug filtration to remove the LiCl by-product. The filtrates were then transferred back to clean reaction vessels where they were concentrated under reduced pressure. With this setup, the automated Matteson homologation was highly successful, furnishing product 2 in high yield (92%) and without human intervention. This approaches the highest achievable yield on the platform, as a control experiment in which an inert internal standard was subjected to the same workflow gave back 94% recovery. To accomplish an automated assembly-line synthesis, iteration of the homologation steps is required. With product 2 available in the reaction vessel, a second Matteson homologation was performed on this new substrate using an identical workflow. Pleasingly, homologated product 3 could be isolated in an overall 77% yield (88% yield/step), thus showing high reproducibility over multiple chemical manipulations. Indeed, in contrast to a manual performance in the laboratory, the robot can operate up to four needles at a time, thus allowing reactions to be run in parallel (ideal to monitor the reproducibility of the methodology). With iterative Matteson homologations optimised, we then focused on the automated chiral carbenoid homologation with lithiated benzoate ester 4-Li, using organostannane 4 as the carbenoid precursor (Fig. ). In the laboratory, 4-Li is generated by treatment of 4 with equimolar amounts (1.3 equiv.) of n-BuLi in Et2O at -78 °C before addition of the boronic ester and subsequent warming to promote 1,2-rearrangement. However, as with the Matteson homologation, some adjustments to the laboratory procedure were required for effective translation to the automated platform (see Supplementary Materials).