4．通过有机金属试剂对醛、酮、环氧、及 羧酸衍生物加成反应 得到醇
有机金属试剂如格氏试剂、有机锂试剂、锌试剂等对醛、酮、环氧、或者羧酸及酯加成可以得到相应的仲醇或叔醇。
一般而言，对于芳香的金属试剂由于锂试剂较易从相应的芳香溴代物或碘代物产生，因此较为多用；有时反应芳香锂盐反应不好时我们就要考虑，用相应的格氏试剂，芳香的格氏试剂可通过相应的芳香溴代物或碘代物与镁反应得到，但当分子内有其他对格氏试剂敏感的官能团存在时，由于制备格氏试剂一般需要回流，因而不能使用该方法制备格氏试剂，此时一般可通过使用iPrMgCl或iPrMgBr在低温下交换得到相应的格氏试剂。产生而烷基的金属试剂一般通过烷基卤代物制成相应的格氏试剂使用；对于a-溴代酯则可通过Reformasky反应得到相应的b-羟基酯。
有许多的活性基团的a-位的氢的酸性是相当高的，常常可以通过强碱拔掉这些a-位的氢得到相应的金属试剂。如芳环（苯环或杂环）上有氟原子时，一般a-位的氢可用LDA拔除得到相应的锂盐;苯环上有甲氧基时，一般a-位的氢可用n-BuLi拔除得到相应的锂盐;吡啶环上有氯或甲氧基的a-位氢可用n-BuLi拔除， 得到相应的锂盐；吡啶的2-位甲基的氢可被LDA拔除得到相应的锂盐；烷基腈、酯或酰胺的a-位氢可通过LiHMDS, NaHMDS, KHMDS, LDA,n-BuLi等拔除得到相应的锂盐；许多杂环的氢也可直接被n-BuLi等拔除得到相应的锂盐如：呋喃，噻吩，噻唑，1,3-嘧啶等；还有Boc保护的环胺的a-位氢可被s-BuLi拔除得到相应的锂盐。
4.1有机金属试剂对醛制备仲醇
和相应的化合物反应来制备各级醇的金属试剂，最常用的是格氏试剂。如和醛反应先生成加成中间产物然后再水解能得到仲醇。加成产物的水解常用稀盐酸或硫酸。如果和甲醛反应则生成伯醇。反应方程式如下所示。
除了格氏试剂外有机锂试剂、有机铝试剂、有机钛试剂、有机锰试剂、有机锌试剂、有机锡试剂、有机钐试剂等与醛反应也可以得到仲醇，如：
4.1.1格氏试剂和
醛制备仲
示例
Under argon atmosphere, 5 ml of 1.0 M tetrahydrofuran solution of ethylmagnesium bromide was diluted with 5 ml of tetrahydrofuran, a tetrahydrofuran (5 ml) solution of 0.30 g of (1H-furo[2,3-g]indazol-1-yl)acetaldehyde was added dropwise, and the mixture was stirred at room temperature for 3 days.. The reaction mixture was poured into ammonium chloride aqueous solution and extracted with ethyl acetate.. The organic layers were combined, washed with brine and then dried with anhydrous magnesium sulfate.. After removal of the solvent, the residue was purified by a silica gel column chromatography to give 0.29 g of 1-(1H-furo[2,3-g]indazol-1-yl)-2-butanol.
4.2有机金属试剂对酮加成制备叔醇
格氏试剂和酮反应可得到叔醇。水解时最好用氯化铵，以避免强酸使叔醇水解。
格氏反应的机理一般认为首先是格氏试剂中带有正电荷的镁离子与羰基氧结合，进而另一分子格氏试剂中的烃基进攻羰基碳原子，形成环状过渡态，经单电子转移生成醇盐，再经水解而得产物。
象醛一样，除了格氏试剂外有机锂试剂、有机铝试剂、有机钛试剂、有机锰试剂、有机锌试剂、有机锡试剂、有机钐试剂等与酮反应也可以得到叔醇。有机锂试剂试剂代替格氏试剂在与位阻酮的加成时更显示了它的优越性。如在低温下，叔丁基锂与二叔丁基酮反应，几乎没有还原的副反应，3而以高产率生成三叔丁基甲醇。
4.2.1有机试剂和
酮制备叔醇
示例
To a solution of (E)-1- {4- [1-ethyl-1- (4-hydroxy-phenyl)-propyl]-2-methyl-phenyl}- pent-1-en-3-one (350 mg, 1.04 mmol) in THF (2 ml), 0.5 M EtLi in THF (10.4 ml, 5.21 mmol) was added at 0 degree and the mixture was stirred at room temperature for 1 h. To the mixture, saturated NH4CI was added, flirted through celite and concentrated in vacuo. The residue was purified by preparative TLC (ethyl acetate/n-hexane = 1/2) to give the title compound (145 mg, 38percent). H-NMR : 0.60 (t, 6H), 0.92 (t, 6H), 1.61 (q, 4H), 2.03 (q, 4H), 2.30 (s, 3H), 5.99 (d, 1 H), 6.70-7. 28 (m, 8H); MS (ESI+) : 349 ([M-OH]+).
4.3有机金属试剂对环氧加成制备醇
有机金属试剂也可以和环氧加成反应制备制备醇。如苯格氏试剂和环氧乙烷的反应。正象羰基的加成反应一样，开环时镁原子连接在氧原子上。水解后生成苯乙醇。
这种方法的特点是可以的得到多两个碳原子的醇。
4.3.1
有机金属试剂对环氧加成制备醇示例
To a solution of (1R,2S)-1-(4,5-diphenyloxazol-2-yl)-1,2-epoxycyclohexane (20 g) and CuBr (3.0 g) in tetrahydrofuran (400 ml) was dropwise added a solution of 3-methoxybenzylmagnesium chloride [prepared from 3-methoxy-benzylchloride (50 g) and Mg (9.2 g)] in tetrahydrofuran (500 ml) at -78.deg. C. under N2.. The mixture was stirred for 2 hours at the room temperature and partitioned between ethyl acetate and water.. The organic layer was washed with 1N-HCl, water, sat. NaHCO3 and brine.. The dried solvent was evaporated in vacuo and the residue was purified by chromatography on silica gel to give (1R,2S)-1-(4,5-diphenyloxazol-2-yl)-1-hydroxy-2-(3-methoxybenzyl)cyclohexane (29.2 g). IR (Nujol): 3400, 1600 cm-1; NMR (CDCl3, d): 1.4-2.4 (9H, m), 3.07 (1H, d, J=10 Hz), 3.52 (1H, m), 3.74 (3H, s), 6.7-6.9 (4H, m), 7.15 (1H, t, J=8 Hz), 7.2-7.8 (10H, m); Mass (m/z): 440 (M+H)+.
4.4有机金属试剂对酸加成制备叔醇
格氏试剂与羧酸一般不发生反应，因为格氏试剂和羧酸生成不溶性的盐，影响进一步的反应：
但是有机锂与羧酸可以发生反应，形成酮，进一步和有机锂反应生成叔醇。羧酸与有机锂试剂先形成羧酸锂盐，羧酸锂盐的离解性能不是很高而溶解性能却很好，且易于接受亲核试剂对酰基碳的进攻，当第二个分子有机锂试剂与羧酸锂反应时，首先是锂与氧接近，使酰基碳更具有正电性，帮助R’向酰基进攻，形成中间物，然后水解得酮。羧酸可以与有机锂试剂合成酮，主要原因是因为羧酸与有机锂试剂能形成稳定的中间物，这个试剂可以等到所有的试剂均反应完后再水解得到酮。
4.4.1有机金属试剂对酸加成制备叔醇示例
(S)-N-acetylphenylalanine (0.5 g, 2.4 mmol) was added to THF (10 mL). As the solution was being stirred, carbonyl di-imidazole (CDI) (0.41 g, 2.54 mmol) was added and the solution was left to stir at room temperature under a nitrogen atmosphere for 1 hr. Meanwhile a solution of lithium t-butylacetate was prepared from butyllithium (1.6 M, 6 mL, 9.6 mmol), [DIISOPROPYLAMINE] (2 mL, 14.4 mol), and t-butylacetate (1.29 mL, 9.6 mmol) at-78 C under N2 atmosphere. The imidazole solution was added dropwise to the pale yellow solution of lithium enolate and left to stir [AT-78 C] for 40 mins before the reaction was quenched with [HC1] (25 mL, 1 M) and extracted with ethyl acetate (3 x 20 mL). The organic extracts were combined, washed with brine (25 mL) and dried before being passed through a short pad of silica, followed by chromatography to give the title compound as an orange oil (0.58 g, 1.9 mmol, 79percent). 'H NMR [(CDC13)] [8] 1.42 (s, 9H), 1.95 (s, [3H0,] 3.02 (dd, 1H, J= 6.5, 14.5 Hz), 3.16 (s, 2H), 4.92 (dd, 1H, J= 6.5, 14 Hz), 6.12 (d, 1H, J= 7 Hz), 7.15-7. 32 (m, [SH].) ESI [NALZ] = 328.2 [(MNA+),] 344.2 [(MI).]
4.5有机金属试剂对酯加成制备叔醇
酯与格氏试剂发生反应，先得到酮，酮继续与格氏试剂反应，得到三级醇，这是一个很有用的合成两个烷基相同的三级醇的方法。甲酸酯与格氏试剂反应得到对称的二级醇。
有机锂化合物与酯也能反应，与格氏试剂一样得到三级醇。但是对于有空间位阻的酮，反应能停留在酮，产率很好：
4.5.1有机金属试剂对酯加成制备叔醇示例
To a solution of ethyl 3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propionate (3.9 g, 12.0 mmol) in THF (100 ml) was added ethylmagnesium bromide (12.0 ml, 36.0 mmol, 3.0M in ether) at room temperature under nitrogen (mild exotherm).. The reaction mixture was stirred for 17 hours at which time it was carefully quenched with NH4Cl (sat., 20 ml).. The precipitated salts were dissolved into water (25 ml) and the layers were separated.. The aqueous phase was extracted with EtOAc (2*) and the combined organics were washed with brine and dried (Na2SO4).. Filtration and concentration gave the crude product which was purified via flash column chromatography (silica gel, 1percent MeOH/DCM) to give 2.4 g (61percent) of the desired product as an oil which solidified on standing, m.p.=50-53.deg. C. ANALYSIS: Calculated for C19H27FN2O2: 68.24percent C 8.14percent H 8.38percent N; Found: 67.99percent C 8.11percent H 8.48percent N