Selective protein modification is essential in the investigation of the function of proteins and in the discovery of therapeutics. Electrophilic small molecules provide opportunities to form selective covalent linkages with nucleophilic amino acids with the reactivity of the warhead critical to the intended application. For targeted therapeutics, sufficient warhead reactivity is required to effectively modify the target residue, whereas over-reactivity can be associated with off-target effects and rapid metabolism. Acrylamides have been successfully incorporated into FDA approved drugs such as Ibrutinib (Fig ). Chemical probes and screening libraries necessarily encompass different ranges of intrinsic reactivity. Moreover, the structure of the warhead itself can afford protein interactions and influence target specificity and proteome coverage by providing alternative geometries and selectivities. Recently, Cravatt demonstrated the application of enantiomeric pair probes to achieve differential interaction between small molecules and proteins in cells. This poses interesting potential for intrinsically chiral warheads, which has yet to be realised. The approach of 'electrophile first' proteomic screening, ensures that ligandable residues (often cysteine) are identified, from which targeted affinity elements can then be developed to ensure selective protein labelling. However, there are few synthetic strategies available to directly modify reactive warheads to grow a hit compound. Indeed, synthetic manipulation of covalent fragments for late-stage modification is extremely challenging due to the nature of the reactive groups. Installation of the warhead in the last step in a sequence is often required, limiting the rapid production of analogues to determine structureactivity relationships. Thus, there is considerable demand for new warheads which can offer both tuneable reactivity and synthetic tractability to enable fragment growth or late-stage diversification. peptides. Recently, Ojida reported BCB amide derivatives as cysteine-directed electrophiles for covalent inhibitor development (Fig ). In parallel, the strain release reactivity of BCBs has seen significant development to form cyclobutanes, through the addition of anions, radicals, and electrophiles, and to form larger ring sizes. Among synthetic developments, Lindsay recently developed a one-pot process to generate BCB sulfones from methyl sulfones. However, there remain few examples of functionalization of intact BCB derivatives: Anderson reported metallation for bridgehead and bridge functionalization on specific sterically hindered amide-BCB derivatives. We envisaged that the novel combination of BCBs and sulfoximines would present attractive, tuneable and chiral 3-D warheads with an increased range of electrophilicity that could be more directly controlled with potential for rapid diversification. Sulfoximines have emerged in recent years in clinical candidates as attractive chiral aza-analogues of sulfones or sulfonamides (Fig ). Specifically, the sulfoximine nitrogen atom introduces a proximal chiral center and additional vector to allow broader exploration of 3-D chemical space and offers the potential to tune the chemical features. Here we report the efficient one-pot synthesis of chiral BCBsulfoximines (Fig and). Further derivatization is demonstrated in the presence of the BCB warhead through Nand C-vectors including cross-coupling reactions and bridgehead deprotonation. The additional tuneable N-vector allows considerably broader strain-release reactivity than BCB sulfones. Moreover, we demonstrate cysteine-selective labelling in whole proteins, and potential for selective labelling in cell lysates.