对于有些结构复杂，带有多种敏感官能团时，以上这些一步或一锅法无法将醛或酮的羰基直接转化为亚甲基，因此可能需要将醛或酮转化为其他官能团进行除去。较为常见的方法是转化为醇羟基除去（醇羟基除去方法见脱羟基反应部分）；另外，可以将醛或酮转化为乙二硫醇的缩醛或酮，再用Raney Ni 氢化还原为亚甲基；另外也有文献将醛或酮转化为对甲苯磺酰肼的腙，再用DiBAL或NaBH(OAc)3还原。
1、醛或酮转化为乙二硫醇的缩醛或酮，再用Raney Ni 氢化还原为亚甲基示例
To a mixture of 1 (2.0 g), acetic acid (30 mL) and ethanedithiol (2 mL) was dropwise added BF3-ethrate (4 mL) at room temperature. The reaction mixture was allowed to stand at room temperature for 6 hr. Ice-water was added and extracted with ether and CHCl3. The combined organic layers washed with NaHCO3 solution until acetic acid was removed, then washed with H2O, dried over Na2SO4. Evaporation of the solvent afforded an oil, which crystallized on standing. Re-crystallization on from EtOH afforded 1.85 g of 2 as needles,mp 134-136oC .
A mixture of 2 (650 mg), Raney Ni (0.9 g) and abs. EtOH (75 mL) was heated under reflux for 7 hr. Then, the catalyst was filtered off and washed with EtOH. The combined filtrates were evaporated under reduced pressure to dryness to give an oil (513 mg), which was dissolved in EtOH (10 mL) and stirred with Raney Ni (300 mg) in hydrogen atmosphere for 4hr. The catalyst was filtered off and washed with EtOH and filtrates were evaporated under reduced pressure to dryness to give an oil (513 mg). This oil was purified via chromatography (benzene/CHCl3 1:1) gave pure 3 (212 mg, 48 %).
Trtsuo Hiraoka and Yukichi Kishida Chem. Pharma Bull. 1968, 16, 1576-1583
The ketone 1 (851 mg, 5 mmol) was heated briefly to boiling with 931 mg (5 mmol) of p-toluenesulfonylhydrazine in 5 mL of methanol. After 24 h at room temperature, the reaction mixture was evaporated to dryness under reduced pressure and washed with pentane to give a crystalline product, 1.7 g (l00 %), mp 190-191 oC. NMR (CDCl3) δ 2.38 (s, 3 H,ArCH3), 3.00 (s, 3 H, OCH3), 3.16 (s, 3 H, OCH3), 7.20 (d, J = 8 Hz, 2 H, ArH), 7.74(d, J =8 Hz, 2 H, ArH).
To 3 (338 mg, 1 mmol) in 2 mL of dry CH2C12 was added at 0 oC under N2 2.5 mL of 0.9 M diisobutylaluminum hydride (DBAL) in hexane. The mixture turned bright yellow after ca. 1 mL of the DIBAL solution was added, and all the tosylhydrazone was dissolved during DIBAL addition. Stirring was continued for 15 min (subsequent reactions showed no increase in yield with extended reaction times), and the solution was carefully decomposed with 2.5 mL of 3 N aqueous NaOH. Extraction with pentane, drying (MgSO4), and distillation of the solvents through an efficient Vigreux column gave a colorless solution containing 103 mg (66%) of 7,7-dimethoxybicyclo[2.2.1] heptane by GC analysis on column B, 80-100 oC. A sample of the product was purified by preparative GC on column D (110oC). It had NMR (CC14) δ 0.9-1.4 (m, 4 H), 1.5-2.0 (m, 6 H), and 3.10 (s, 6 H, 2 OCH3) ppm and MS m/e (rel intensity) 156 [M+], 101 (100).
David A. Lightner, Jacek K. Gawrohski, and Thomas D. Bouman, J. Am. Chem.Soc. 1980，102，1983-1990
近 来 , 哈佛的Andrew Myers 在其关于腙衍生物工作中报导了有效的低温Wolff-Kishner还原. 在Sc(OTf)3催化下, 用TBS-NH-NH-TBS与酮或醛成腙, 再加入 tBuOH/tBuOK 在DMSO中可将粗品腙进行有效的低温Wolff-Kishner还原成10. 另外,可以对酮腙卤化可得烯卤化物如11, 或根据不同的条件制得 1,1-二卤化物. 对醛腙卤化可得1,1-二卤化物如13.
Michael E. Furrow and Andrew G. Myers J. Am. Chem. Soc. 2004, 126, 5436-5445