D'Oca M G, Moraes L A, Pilli R A, Eberlin M N
State University of Campinas - UNICAMP, Institute of Chemistry, CP6154, 13083-970 Campinas, SP Brazil.
J Org Chem. 2001 Jun 1;66(11):3854-64. doi: 10.1021/jo005778h.
The intrinsic gas-phase reactivity of cyclic N-alkyl- and N-acyliminium ions toward addition of allyltrimethylsilane (ATMS) has been compared using MS(2) and MS(3) pentaquadrupole mass spectrometric experiments. An order of electrophilic reactivity has been derived and found to agree with orders of overall reactivity in solution. The prototype five-membered ring N-alkyliminium ion 1a and its N-CH(3) analogue 1b, as well as their six-membered ring analogues 1c and 1d, lack N-acyl activation and they are, accordingly, inert toward ATMS addition. The five- and six-membered ring N-acyliminium ions with N-COCH(3) exocycclic groups, 3a and 3b, respectively, are also not very reactive. The N-acyliminium ions 2a and 2c, with s-trans locked endocyclic N-carbonyl groups, are the most reactive followed closely by 3c and 3d with exocyclic (and unlocked) N-CO(2)CH(3) groups. The five-membered ring N-acyliminium ions are more reactive than their six-membered ring analogues, that is: 2a > 2c and 3c > 3d. In contrast with the high reactivity of 2a, its N-CH(3) analogue 2b is inert toward ATMS addition. For the first time, the transient intermediates of a Mannich-type condensation reaction were isolated-the beta-silyl cations formed by ATMS addition to N-acyliminium ions-and their intrinsic gas-phase behavior toward dissociation and reaction with a nucleophile investigated. When collisionally activated, the beta-silyl cations dissociate preferentially by Grob fragmentation, that is, by retro-addition. With pyridine, they react competitively and to variable extents by proton transfer and by trimethylsilylium ion abstraction-the final and key step postulated for alpha-amidoalkylation. Becke3LYP/6-311G(d,p) reaction energetics, charge densities on the electrophilic C-2 site, and AM1 LUMO energies have been used to rationalize the order of intrinsic gas-phase electrophilic reactivity of cyclic iminium and N-acyliminium ions.
利用串联质谱（MS(2)）和三级串联质谱（MS(3)）五极杆质谱实验，比较了环状N - 烷基和N - 酰基亚胺离子与烯丙基三甲基硅烷（ATMS）加成反应的本征气相反应活性。推导了亲电反应活性顺序，发现其与溶液中的总反应活性顺序一致。原型五元环N - 烷基亚胺离子1a及其N - CH₃类似物1b，以及它们的六元环类似物1c和1d，缺乏N - 酰基活化作用，因此对ATMS加成反应呈惰性。分别带有N - COCH₃外环基团的五元环和六元环N - 酰基亚胺离子3a和3b，反应活性也不是很高。具有s - 反式锁定内环N - 羰基的N - 酰基亚胺离子2a和2c反应活性最高，紧随其后的是带有外环（且未锁定）N - CO₂CH₃基团的3c和3d。五元环N - 酰基亚胺离子比其六元环类似物反应活性更高，即：2a > 2c且3c > 3d。与2a的高反应活性形成对比的是，其N - CH₃类似物2b对ATMS加成反应呈惰性。首次分离出了曼尼希型缩合反应的瞬态中间体——由ATMS加成到N - 酰基亚胺离子上形成的β - 硅基阳离子——并研究了它们在气相中对解离以及与亲核试剂反应的本征行为。当受到碰撞活化时，β - 硅基阳离子优先通过格罗布碎裂（即逆加成）解离。与吡啶反应时，它们通过质子转移和三甲基硅鎓离子夺取反应进行竞争，反应程度各不相同——这是α - 酰胺烷基化反应假定的最后关键步骤。采用Becke3LYP/6 - 311G(d,p)反应能量学、亲电C - 2位点上的电荷密度以及AM1最低未占分子轨道能量，对环状亚胺离子和N - 酰基亚胺离子本征气相亲电反应活性顺序进行了合理化分析。
