Sulfoximines have gained considerable recognition as an important structural motif in drug discovery of late. In particular, the clinical kinase inhibitors for the treatment of cancer, roniciclib (pan‐CDK inhibitor), BAY 1143572 (P‐TEFb inhibitor), and AZD 6738 (ATR inhibitor), have recently drawn considerable attention. Whilst the interest in this underrepresented functional group in drug discovery is clearly on the rise, there remains an incomplete understanding of the medicinal‐chemistry‐relevant properties of sulfoximines. Herein we report the synthesis and in vitro characterization of a variety of sulfoximine analogues of marketed drugs and advanced clinical candidates to gain a better understanding of this neglected functional group and its potential in drug discovery.

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Indium-mediated allylation of N-tert-butanesulfinyl ketimines afforded in high yields and diastereoselectivities homoallylic amine derivatives with the nitrogen atom bonded to a quaternary stereocenter.

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The palladium-catalyzed allylation of N-tert-butanesulfinyl imines with allylic alcohols in the presence of InI as reducing reagent takes place with high diastereoselectivity in reasonable yields. The reaction with crotyl alcohol is totally regioselective, leading to the antidiastereomer as the main reaction product.The stereoselective allylation of imines using organometallic compounds is of great interest in synthetic organic chemistry because the resulting homoallylic amines are valuable building blocks. 1 For instance, the double bond of the allylic moiety can participate in a number of further synthetically useful transformations: hydroboration, hydration, epoxidation, hydroformylation, ozonolysis, olefin metathesis, etc. 2 Among the stereoselective methodologies, the catalytic enantioselective allylations 3 rely on the use of chiral Lewis acids or chiral Lewis bases. In addition, double activation could be also achieved by using chiral bifunctional catalysts 4 by the simultaneous activation of both electrophilic and nucleophilic reaction partners through a cooperative action of different functionalities of the ligand. However, and in spite of the rapid evolution of catalytic methods in recent years, the use of stoichiometric reagents (including substrates and/or allylic organometallic partners) is still the favourite choice of organic chemists in the synthesis of key intermediates of natural products. In these diastereoselective allylations, 5 the stereochemical information can be transferred by substrate control, including chiral auxiliaries, or through the use of chiral reagents (reagent control). Sometimes a double induction could also be involved in the process, a match/mismatch effect being possible. Performing the stereoselective allylation of imine derivatives with allylic halides in the presence of reducing metals under Barbier-type reaction conditions (metalation in the presence of the electrophile) is also of interest, because this strategy circumvents the need of isolating allyl metal species (the real nucleophiles), which usually are sensitive, and in many cases also toxic. The most commonly used metals in these transformations are chromium, 6 indium 7 and zinc. 8 Particularly noteworthy is the use of allylic alcohols as allylating reagents of carbonyl compounds and imines under palladium catalysis in the presence of a reducing reagent. 9 More recently, the use of the Kulinkovich reagent in the coupling of allylic alcohols with aldimines provides an alternative approach to regio-and stereodefined homoallylic amines. 10 On the other hand, in the growing field of the synthetic applications of chiral N-tert-butanesulfinyl derivatives, 11 we reported the diastereoselective allylation 12 of N-tert-butanesulfinyl aldimines 13 and ketimines 14 with in situ generated allylindium reagents, and the first one-pot a-aminoallylation of aldehydes with chiral tert-butanesulfinamide, allylic bromides, and indium, which provides homoallylic amines with high chemoand stereoselectivities. 15 The chiral auxiliar...