TaMe₃Cl₂‐Catalyzed Intermolecular Hydroaminoalkylation: A Simple Complex for Enhanced Reactivity and Expanded Substrate Scope

Abstract

Tantalizingly simple: The common organometallic starting material TaMe3Cl2 can be used for the catalytic CH functionalization reaction, hydroaminoalkylation. The substrate scope for this readily accessed compound includes unactivated terminal and internal alkenes, styrene derivatives, and both alkylaryl‐ and dialkyl secondary amines (see scheme).

A Commercially Available Tantalum Catalyst for the Highly Regioselective Intermolecular Hydroaminoalkylation of Styrenes

“…As can be seen from Table 1, the initial experiment performed under standard conditions {10 mol‐% [Ta(NMe 2 ) 5 ], hexanes, 140 °C, 96 h, sealed tube; Table 1, Entry 1}7g already gave access to the pure branched hydroaminoalkylation product 5a in 93 % isolated yield. Interestingly and in good agreement with the results obtained with group 5 metal catalysts with more complex ancillary ligands,8i–8k the regioselectivity of the hydroaminoalkylation reaction was 98:2 in favor of the branched isomer 5a , as determined by GC analysis of the crude reaction mixture prior to chromatographic purification. A short optimization study then revealed that significantly lower yields of 5a are obtained at lower reaction temperatures of 120 or 100 °C (Table 1, Entries 2 and 3) or with shorter reaction times (16–72 h; Table 1, Entries 4–6).…”

“…The first successful hydroaminoalkylation reactions of styrenes catalyzed by group 5 metal catalysts have only been realized very recently with binaphtholate8i or phosphoramidate8j complexes as well as with [TaMe 3 Cl 2 ] 8k. In all of these cases, the branched product was always formed as the major regioisomer, and selected reactions could even be performed at room temperature 8j.…”

Hydroaminoalkylation of Allylsilanes and a One‐Pot Procedure for the Synthesis of 1,5‐Benzoazasilepines

“…For that purpose, ah ydroaminoalkylation reaction mixture of allylsilane 21 and N-methylaniline (1)i nt oluene was initially heatedt o1 40 8Cf or 24 hi nt he presence of 10 mol %o fc atalyst IV.A fterwards, 2.5 mol %P d 2 (dba) 3 ,7mol %R uPhos, sodium tert-butoxide and additional toluene were added and the resulting reactionm ixture was heatedt o1 10 8Cf or additional 24 h. The yield of 83 % in which 1,5-benzoazasilepine 23 was obtained after chromatographic purification ( Table 5, entry 1) again underlines the wellestablished fact that the Buchwald-Hartwig amination tolerates the presence of the reagents used in hydroaminoalkyla-tion reactions. To finally investigate the scope of the onepot procedure, we then reacteda dditional ortho-, meta-, and para-substituted N-methylanilines with allylsilane 21.A se xpecteda nd in good agreement with the results obtained for the hydroaminoalkylation of simple allylsilanes presented in Ta ble 2, it was found that para-o rmeta-substituted N-methylanilinesu ndergo smooth reactiont og ive the desired 1,5-benzoazasilepines in good yields between 66 and 84 %( Ta ble 5, entries [3][4][5][6][7][8][9][10][11]. To finally investigate the scope of the onepot procedure, we then reacteda dditional ortho-, meta-, and para-substituted N-methylanilines with allylsilane 21.A se xpecteda nd in good agreement with the results obtained for the hydroaminoalkylation of simple allylsilanes presented in Ta ble 2, it was found that para-o rmeta-substituted N-methylanilinesu ndergo smooth reactiont og ive the desired 1,5-benzoazasilepines in good yields between 66 and 84 %( Ta ble 5, entries [3][4][5][6][7][8][9][10][11].…”

“…[7] The corresponding reaction sequence includes an initial highly regioselective titanium-catalyzed intermolecularh ydroaminoalkylation, [8,9] which takes place by the addition of an a-C(sp 3 )ÀHbond of an N-methylaniline across aC ÀCd ouble bond of an N-allyl-2-bromoaniline, and as ubsequenti ntramolecular Buchwald-Hartwig amination (Scheme 1, path A). [11] Interestingly,b yc hoosing allyl(2-bromophe-nyl)silanes as starting materials, the literature-unknown silicon analogues of 1,5-benzodiazepines, so-called 1,5-benzoazasilepines (Scheme 1, path B), should be accessible by ao ne-pot procedure that is similart oo ur 1,5-benzodiazepine synthesis. However,int his contextitm ust be noted that Schafer et al already achieved the hydroaminoalkylation of allyltrimethylsilane with N-methylanilineinthe presenceo fatantalum catalyst.…”

“…However,int his contextitm ust be noted that Schafer et al already achieved the hydroaminoalkylation of allyltrimethylsilane with N-methylanilineinthe presenceo fatantalum catalyst. [11] Interestingly,b yc hoosing allyl(2-bromophe-nyl)silanes as starting materials, the literature-unknown silicon analogues of 1,5-benzodiazepines, so-called 1,5-benzoazasilepines (Scheme 1, path B), should be accessible by ao ne-pot procedure that is similart oo ur 1,5-benzodiazepine synthesis. In this context,i th as to be mentioned that Voronkov et al [12] as well as Tacke et al [13] already synthesized closely related 1,4azasilepanes, which lack the benzo-annulation of the sevenmembered ring, by using alternative strategies and very recently,alot of effort hasb een spent on the developmento f new pathways for the enantioselective synthesis of closely related 1,5-benzothiazepines.…”