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Tert-Butanesulfinamides As Nitrogen Nucleophiles in Carbon-Nitrogen

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Tert-Butanesulfinamides As Nitrogen Nucleophiles in Carbon-Nitrogen tert-Butanesulfinamides as Nitrogen Nucleophiles in Carbon-Nitrogen Bond Forming Reactions Johana Ramirez Hernandez, Fabrice Chemla, Franck Ferreira, Olivier Jackowski, Julie Oble, Alejandro Perez-Luna, Giovanni Poli To cite this version: Johana Ramirez Hernandez, Fabrice Chemla, Franck Ferreira, Olivier Jackowski, Julie Oble, et al.. tert-Butanesulfinamides as Nitrogen Nucleophiles in Carbon-Nitrogen Bond Forming Reactions. CHIMIA, Schweizerische Chemische Gesellschaft, 2016, 70 (1), pp.84-92. 10.2533/chimia.2016.84. hal-01292458 HAL Id: hal-01292458 https://hal.sorbonne-universite.fr/hal-01292458 Submitted on 23 Mar 2016 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. 84 CHIMIA 2016, 70, No. 1/2 The French connecTion doi:10.2533/chimia.2016.84 Chimia 70 (2016) 84–92 © Swiss Chemical Society tert-Butanesulfinamides as Nitrogen Nucleophiles in Carbon–Nitrogen Bond Forming Reactions Johana Ramirez Hernandez, Fabrice Chemla, Franck Ferreira, Olivier Jackowski, Julie Oble, Alejandro Perez-Luna*, and Giovanni Poli Abstract: The use of tert-butanesulfinamides as nitrogen nucleophiles in carbon–nitrogen bond forming reac- tions is reviewed. This field has grown in the shadow of the general interest in N-tert-butanesulfinyl imines for asymmetric synthesis and occupies now an important place in its own right in the chemistry of the chiral amine reagent tert-butanesulfinamide. This article provides an overview of the area and emphasizes recent contribu- tions wherein the tert-butanesulfinamides act as chiral auxiliaries or perform as nitrogen donors in metal-cata- lyzed amination reactions. Keywords: Amination · tert-Butanesulfinamide · Chiral nucleophiles 1. Introduction In this context, the performance of charged sulfur atom means that the tert-bu- tert-butanesulfinamides as nitrogen nu- tanesulfinyl group attenuates considerably Chiral amine reagent tert-butanesulfin- cleophiles raises increasing interest. On the nucleophilicity of the nitrogen atom of amide (1) has received massive attention the one hand it represents a possibility to tert-butanesulfinamides. Leaving aside the over the last decade and has found applica- elaborate further the α-branched amines above-mentioned condensation reactions tions in an ever-increasing number of re- produced from additions to N-tert-bu- with aldehydes and ketones that have been search areas.[1] In the field of asymmetric tanesulfinyl imines (Scheme 1, A). On the reviewed previously[1] and will not be dis- synthesis, it is now a well-established tool other hand, a number of recent reports have cussed here, reactions with carbon electro- for the preparation of chiral non-racemic evidenced that tert-butanesulfinamides can philes are essentially of two types: (i) those amines. Rapid access to both enantiomeric perform as chiral nitrogen nucleophiles in that rely on the intermediate formation of a forms of tert-butanesulfinamide, high lev- nucleophilic amination reactions produc- main-group metal amide and (ii) those, less els of stereodiscrimination and easy re- ing a new stereocenter, and that stereoin- common, that involve a transition-metal moval of the sulfinyl moiety under mild duction is possible with excellent levels catalyzed process. acidic conditions constitute major advan- of diastereoselectivity (Scheme 1, B). The tages to the use of the tert-butanesulfinyl purpose of this article is to showcase the group as chiral auxiliary on nitrogen. possibilities offered by the use of tert-bu- 2. Reactions Involving Metallated Asymmetric synthesis of enantiopure chi- tanesulfinamides as nitrogen nucleophiles N-tert-Butanesulfinamides as ral amines using tert-butanesulfinamide in asymmetric synthesis and to emphasize Nucleophiles usually follows a well-established pattern the recent contributions wherein the sulfi- that entails condensation with a carbonyl nyl moiety acts as chiral auxiliary. Main-group anions of tert-butanesul- derivative and a subsequent reaction at the The combination of the steric bulk of finamide (1) and its N-substituted conge- electrophilic carbon atom of the N-sulfinyl the tert-butyl moiety and the electron- ners react readily with an array of carbon imine thereby produced (Scheme 1, A).[1] withdrawing effect of the positively electrophiles. Their good resistance to A: tert-Butanesulfinyl imines as chiral electrophiles: functionalization by chiral C–Nbond formation induction O O O O O – S 2 S + E S S R1 N tBu R HN tBu E N tBu H N tBu 2 * * R1 1 2 1 2 1 R R R R B: tert-Butanesulfinamidesaschiral nucleophiles : chiral induction R1 R2 O *Correspondence: Dr. A. Perez-Luna O R S N tBu Sorbonne Universités R S LG stereoselective UPMC Univ Paris 06, UMR CNRS 8232 N tBu * C–Nbond formation Institut Parisien de Chimie Moléculaire H R1 R2 F-75005, Paris, France E-mail: [email protected] Scheme 1. Uses of tert-butanesulfinamides as nucleophiles in asymmetric synthesis. The French connecTion CHIMIA 2016, 70, No. 1/2 85 racemization makes them privileged inter- cally pure form. For most of the reported With stronger bases such as NaH- mediates to carry out N-functionalization examples, the cyclization precursors are MDS[14] or LiHMDS[15] in DMF, ring- without losing the chiral information on α-branched sulfinamides obtained from closure has been obtained at much lower the sulfur atom. Strategies for N-alkylation N-tert-butanesulfinyl imines and, with temperatures (–40 °C) as for the formation and N-acylation have been developed as the notable exception of aziridine forma- of 4. well as aza-Michael reactions. tion, the carbon undergoing substitution The preparation of diazaspiro[3.3] is primary. Heterocyclizations leading to heptane 5[16] by intramolecular alkylation 2.1 N-Alkylation of tert-Butanesul- the formation of rings ranging from 3 to triggered with tBuOK in THF, evidences finamides 7 members have been accomplished and that four-membered heterocyclization is N-alkylationoftert-butanesulfinamides a rather large variety of reagents and con- also possible with tert-butanesulfinamide can be achieved by deprotonation and elec- ditions have been described (Scheme 2). nucleophiles, but such reactions are not trophilic trapping of the corresponding A possible reason for this is the absence common. By contrast, five-membered ring metal amide with alkyl halides. In the case of a truly general cyclization method and formation by displacement of a halide leav- of tert-butanesulfinamide (1), the process the fact that, quite often, ring closure for ing group is far more usual and has been is complicated by competitive dialkylation a given substrate-type or cyclisation mode implemented in several ways (Scheme 2). and, even if treatment with KOH can be only proceeds under precise experimental It has been accomplished either at 50 °C a solution to obtain N-monoalkylation,[2] conditions (base, solvent, temperature, by treatment with KOH in H O/THF[17] or 2 reductive amination approaches are gen- …). Thus, the correct choice of these con- tBuOK in iPrOH,[13] or at room tempera- erally preferred.[3] The strategy is thus ditions is a key element to achieve the de- ture in THF using LiHMDS[18] (see the most useful for the functionalization of N- sired transformation. formation of 6), KHMDS,[19] or a combi- substituted tert-butanesulfinamides. Not Cyclization of β-chloro N-tert-butane- nation of NaH and a crown ether additive only are these products widely accessible sulfinamides to aziridines is a favorable (15-Crown-5).[20] As illustrated with 7, the through nucleophilic addition or reduction reaction that has been achieved at high latter conditions are tolerant of functional- of tert-butanesulfinyl imines, but also in- temperature by treatment with KOH in ized substrates. It is also noteworthy that troduction of a second nitrogen substituent H O/THF,[11] as illustrated with the prepa- efficient pyrrolidine formation has been 2 is not possible by reductive amination. ration of 2 (Scheme 2), K CO in acetone, described by intramolecular displace- 2 3 Metallation of N-alkyl tert-butanesul- as shown with 3,[12] or tBuOK in iPrOH.[13] ment of mesylate[21] or tosylate[22] leaving finamides can be carried out conveniently using mainstream strong bases such as KH, NaH, LiHMDS, KHMDS or nBuLi. The O O tBu S Conditions O tBu most used solvents are THF or DMF and S S N tBu R2 NH often the reactions are performed at tem- R2 N 1 n peratures higher than –30 °C. Regioselec- R X n tive N-alkylation is generally obtained, but enantiopure enantiopure the competitive S-alkylation might ham- O tBu O tBu O tBu S per the process in the case of substrates O tBu S S S N where the sulfinyl nitrogen is sterically O N N N H Me Cl Me hindered.[4] Me MeO Cl Ph Me Me OBoc N 2.1.1 Intermolecular N-Alkylation Me Ts Reactions 2:73% (X=Cl) 3:88% (X=Cl) 4:85% (X=Cl) 5:84% (X=Br) Conditions: Conditions: Conditions: Conditions: Reports on intermolecular N-alkylation KOH (3.0 equiv) K2CO3 (3.0 equiv) NaHMDS (1.0 equiv) tBuOK (1.4 equiv) reactions of metallated tert-butanesulfin- THF:H2O(1:1) acetone DMF THF amides with non-activated alkyl halides 50 °C,24h reflux, 24 h –40°C, 20 min 0°C, 20 min other than methyl iodide[5] are rare.[6] By O tBu O tBu S O tBu O tBu contrast, allylic and propargylic halides are S S S N well-suited electrophiles that permit inter- N N N Ph MOMO MOMO molecular allylation and propargylation N reactions that are particularly important PMBO Boc from an applicative point of view.
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