硫代缩醛(酮)法

酸催化下，羰基与硫醇或者二硫醇反应生成硫代缩醛(酮)也是羰基保护常用的方法。与缩醛(酮)酸敏感性不同，硫代缩醛(酮)对酸更稳定，酸性条件下水解脱除一般无效，多采用重金属离子如Hg²⁺、 Ag¹⁺、Fe³⁺或其他氧化剂如NBS、I₂、DDQ 或mCPBA等氧化脱除。硫代缩醛(酮)也有非环的和环状的两种，其中非环状比环状容易脱除。

相比常规缩醛(酮)，硫代缩醛(酮)更容易形成，这对一些位阻大活性低的羰基保护可能优势明显，而且其酸性条件稳定性更好，某些时候这一特性可能非常有用，但是硫代缩醛(酮)也有它自身的缺点——环境不友好。首先，脱保护过程很多时候要用到重金属氧化，比常规缩醛(酮)酸性水解条件更苛刻；为了解决这一问题，人们开发了单硫缩醛(酮)：

其稳定性介于缩醛(酮)和硫代缩醛(酮)之间，既可以氧化脱保护也可以酸性水解。其次，硫代缩醛(酮)形成过程中用到的小分子硫醇或者二硫醇有令人难以忍受的恶臭，这也限制了他的应用。好在有一些无臭的硫代试剂可以很好的克服这一问题如：

非环和环状硫代缩醛(酮)由羰基与硫醇或者二硫醇酸催化反应而成，由于硫醇沸点低，易挥发产生恶臭气味，所以人们更愿意使用二硫醇，故环状硫代缩醛(酮)比非环状的应用更加广泛，最具代表性的非环和环状硫代缩醛(酮)如图所示：

其形成和脱除典型操作如下：

应用举例1:

A mixture of 1,3-propanedithiol (7.50 mL, 75.0 mmol), boron trifluoride etherate (9.5 mL, 75.0 mmol), and glacial acetic acid (18.0 mL, 0.32 mol) in dichloromethane(125 mL) was cooled to -20 ^oC. To the vigorously stirred mixture was added slowly a solution of 2-methyl-2-pentenal (8.55 mL, 75.0 mmol) in CH₂Cl₂ (50 mL) while maintaining the temperature between -20 and -15 ^oC. The reaction mixture was stirred for 1 h at -20 ^oC, and then siphoned into ice-cold 10% aqueous KOH solution. The temperature was maintained below 5 ^oC during the quench. After dilution with diethyl ether, the organic phase was separated, washed with 10% KOH, water, brine, and dried (Na₂SO₄). Concentration in vacuum yielded 13.9 g(99%) of the crude dithiane as a 10:1 mixture of E/Z isomers. The dithiane was used without further purification in the next step. (H.Stephen, F. Thilo, Tetrahedron, 2011, 67, 9870)

应用举例2:

NaHCO₃(6.183 g, 73.6 mmol) and I₂ (9.209 g,36.3 mmol) were added to a solution of dithiane (3.34 g,11.0 mmol) in aqueous acetone (94 mL of acetone plus 17 mL water). The resulting mixture was stirred at 0 ^oC for 30 min until TLC showed complete disappearance of starting material. The reaction was quenched with saturated aqueous Na₂S₂O₃ and the mixture was diluted with Et₂O. The phases were separated and the aqueous layer was extracted with Et₂O. The combined organic layers were washed with saturated aqueous Na₂S₂O₃, water, and brine, dried over Na₂SO₄, and concentrated on a rotary evaporator. The residue was purified by column chromatography on silica gel (2:1n-hexane/EtOAc) to give ketone as a yellowish oil (3.892 g, yield 83%). (H-X.Jin, Q. Zhang, H-S. Kim, Tetrahedron, 2006, 62, 7699)