REACTIONS OF AMMONIUM-SALTS WITH BUTYLLITHIUM AND WITH LITHIUM HYDRIDE - NEW ROUTES TO FULLY ANHYDROUS INORGANIC LITHIUM COMPLEXES
REACTIONS OF AMMONIUM-SALTS WITH BUTYLLITHIUM AND WITH LITHIUM HYDRIDE - NEW ROUTES TO FULLY ANHYDROUS INORGANIC LITHIUM COMPLEXES
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DOI：
10.1021/ja00259a053
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发表时间：
1987-12-09
影响因子：
15
通讯作者：
WADE, K
中科院分区：
文献类型：
--
作者：
BARR, D;SNAITH, R;WADE, K
“(i) TMS-咪唑/CH2Cl2；(ii)(CF3SO2) 20/r-Bu2Me-吡啶/CH2C12，0℃（H3O+ 后处理）；(ill) n-Bu4N+ r/CH3CN，70℃，20 分钟；(iv) 3.0 Mhc1，70℃，15 分钟；(v) n-Bu4N+ F7CH3CN，70℃，60分钟；(vi)NaH/THF回流；(vii)TBDMS-Cl/咪唑/DMF；(viii)20/TEA/Z-Bu2Me-吡啶/CH2Cl2，0℃；(ix)TsOH/MeOH酸。 方案I中总结了叔磺酰胺与醇盐的反应。 13 事实上，当 MK-801 (9) 的三氟甲酰胺衍生物在回流乙腈中用甲醇钠处理时，唯一观察到的反应是磺酰基从氮上缓慢去除，而不是三氟甲基化物的损失，如果将此机制应用于醇盐氧与 5 磺酰基的分子内反应，则不会期望观察到产物 7 保留。因此，该过程的分子内性质以及三氟甲基化物离去基团的稳定性（CHF3 的 pÁ" a= 25） 14 可能导致了这一独特的观察。如方案I所示，涉及五配位硫的过渡态或中间体应要求进入的氧占据三角双锥体的轴向位置。由于 N 和引入的 O 原子是五元环的一部分，因此 N 必须占据赤道位置，从而产生两种可能的异构体 a 和 b。出于同样的原因，高电负性的 CF3" 离去基团应占据轴向位置（异构体 a），从而生成产物 7。因此，如果首先形成异构体 b，则它必须通过假旋转或十字转门旋转异构化为异构体 a。 15d 为了进一步定义该反应的范围，我们制备了 3-氟胺 I06a· 9· 73-0 和无环/3-氟胺 1 j6b, 9, 7a, c, d an (j j26b'9'7aAd 分别衍生自 (-)-麻黄碱和 (-)-伪麻黄碱（方案 II）。在这些情况下，需要将羟基作为其甲硅烷基醚进行短暂保护，以便将磺化直接磺化为氮。在所有情况下，我们都通过分离无环化合物（例如 137a 和 147a）或环状氨基磺酸酯（例如，I56b9.7a.«）中间体11和12是作为含碳氟的差向异构体的混合物获得的，16我们的方法提供了这些化合物的立体特异性17途径，该途径也适用于18F标记，尝试使用三氟甲磺酸酐将氨基醇16转化为三氟甲磺酸酯17。氨基磺酸盐
“(i) TMS-imidazole/CH2Cl2;(ii)(CF3S02) 20/r-Bu2Me-pyridine/CH2C12, 0 C (H30+ workup);(ill) n-Bu4N+ r/CH3CN, 70 C, 20 min;(iv) 3.0 Mhc1, 70 C, 15 min;(v) n-Bu4N+ F7CH3CN, 70 C, 60 min;(vi) NaH/THF reflux;(vii) TBDMS-Cl/imidazole/DMF;(viii)(CF3S02) 20/TEA/Z-Bu2Me-pyridine/CH2Cl2, 0 C;(ix) TsOH/MeOH. acid. The overall reaction pathway is summarized in Scheme I. Reaction of tertiary sulfonamides with alkoxide under vigorous conditions normally results in cleavage of the SN bond. 13 Indeed, when the triflamide derivative of MK-801 (9) is treated with sodium methoxide in refluxing acetonitrile, the only observed reaction is the slow removal of the sulfonyl group from nitrogen rather than loss of trifluoromethide. If this mechanism applied to the intramolecular reaction of the alkoxide oxygen with the sulfonyl group of 5, one would not expect to observe the product 7 retaining the SN bond. Therefore, it is likely that the intra-molecular nature of the process as well as the stability of the trifluoromethide leaving group (pÁ" a= 25 for CHF3) 14 leads to this unique observation. As shown in Scheme I, a transition state or intermediate involving a pentacoordinate sulfur should require that the incoming oxygen occupy an axial position of the trigonal bipyramid. Because the N and incoming O atoms are part of a five-membered ring, the N must occupy an equatorial position, thus giving rise to two possible isomers a and b. By the same token, the highly electronegative CF3" leaving group should occupy an axial position (isomer a) which would lead to theproduct 7. Therefore if isomer b is formed first, it must isomerize to isomer a via pseudorotation or turnstile rotation. 15d To further define the scope of this reaction we have prepared the-fluoroamine I06a· 9· 73-0 and the acyclic/3-fluoroamines1 j6b, 9, 7a, c, d an (j j26b'9’7aAd derived from (-)-ephedrine and (-)-pseudoephedrine, respectively (Scheme II). In these cases, transient protection of the hydroxyl groups as their silyl ethers was required in order to direct the sulfonation to nitrogen. In all cases, we have shown the intermediacy of cyclic sulfamates by the isolation of the acyclic (eg, 137a and 147a) or cyclic sulfamate (eg, I56b9. 7a.«) intermediates. In contrast to the previous syntheses inwhich 11 and 12 were obtained as a mixture of epimers at the carbon-bearing fluorine, 16 our methodology provides a stereospecific17 route to these compounds which is also amenable to 18F labeling. Attempts to convert the amino alcohol 16 to the triflate 17 by using triflic anhydride or to thecyclic sulfamate