Ley-Griffith氧化，又被稱為TPAP氧化。
TPAP（nPr4N+RuO4-；TetraPropylAmmonium Perruthenate）對空氣、水分穩(wěn)定，能溶于有機溶劑和水。TPAP相比起四氧化釕的氧化力要弱，底物中若含雙鍵，不會被氧化斷裂，伯醇僅氧化到醛，不會過度氧化為羧酸。實驗步驟簡單，反應(yīng)進行的也非?？臁Ａ硗?，因反應(yīng)條件也很溫和(Reviews: Ley, Synthesis, 1994, 639)，反應(yīng)為均相，常用于對復(fù)雜分子的氧化，其高度的化學(xué)選擇性對許多其它官能團不產(chǎn)生影響，例如：烯鍵、炔鍵、內(nèi)酯、環(huán)氧，甚至縮醛、硅醚、四氫吡醚等。
使用4-甲基嗎啉-N-氧化物 (NMO) 或者其它氧化劑作為助氧化劑時，TPAP可以催化量地使用，反應(yīng)一般在室溫下進行，這樣可以溫和，高效，選擇的氧化醇羥基生成醛和酮，它在氧化反應(yīng)中具有不可取代的地位。對帶有酸敏基團或者多官能團取代底物的氧化反應(yīng)，選擇TPAP/NMO組合試劑是非常合適的。
General Procedure ：
Between 0.02 and 0.15, typically 0.05 equiv. of TPAP are slowly added to a ca. 0.02–0.3 M solution of the alcohol in DCM, containing ca. 0.2–0.7 g of 4? molecular sieves per mmol of alcohol and ca. 1.1 to 2.5, typically 1.5 equiv. of NMO. The resultant mixture is stirred at room temperature till most of the alcohol is consumed.
?
work-up A:
The reaction mixture is filtered through a pad of Celite or silica gel and the resulting solution is concentrated, providing a residue that may need further purification. When the oxidation is performed in the presence of acetonitrile as solvent, as it tends to wash residual TPAP through the Celite or silica pad, it is advisable to evaporate the solvents and add some DCM before the filtering.
work-up B:
?
The reaction mixture is washed with a saturated Na2SO3 aqueous solution, a saturated CuSO4 aqueous solution and, optionally, with brine. Sometimes, it is advisable to add some organic solvent like DCM or EtOAc, in order to facilitate the washings. The organic phase is dried (MgSO4) and concentrated, giving a residue that may need further purification.
TPAP能用（短硅膠柱）除掉。用Na2SO3還原NMO后，水洗就能從產(chǎn)物中除掉。大量反應(yīng)時，較難控制反應(yīng)平穩(wěn)進行、所以加NMO?TPAP要非常注意。
如果感覺NMO在反應(yīng)體系中已大量存在，反應(yīng)卻依然不進行時，繼續(xù)加入NMO反應(yīng)也不會進行了。反應(yīng)溶劑一般是二氯甲烷（DCM）、但用乙腈作共溶劑能提高收率。
反應(yīng)機理
釕（VII）和釕（VI）具有氧化活性。該反應(yīng)機理相比起下圖復(fù)雜，因為反應(yīng)類似自催化反應(yīng) (反應(yīng)一旦開始后會加速)。水的存在會阻礙此自催化過程，所以作反應(yīng)要添加一些4A分子篩除水。NMO是釕的助氧化剤，這樣，TPAP的量可以縮小到催化劑量。
反應(yīng)實例
Tetrapropylammonium perruthenate (16 mg, 0.0468mmol), N-methylmorpholine -N-oxide (0.16 g,1.4 mmol), and 3? molecular sieves (0.47 g)were added to a solution of alcohol (400 mg, 0.94 mmol) in dichloromethane (10mL). The mixture was stirred at room temperature for 30 min then filteredthrough a Celite? pad and the solvent evaporated in vacuo. Flash chromatographyof the residue using 10% diethylether - hexane as eluent afforded 2,8-Bis(tert-butyldimethylsilyloxy) undec-10-en-6-yn-5-one (385 mg, 98%) as colorless oil.
Reference: ARKIVOC 2001 (i) 74-87
