Carbon-Carbon Bond Formation by the Aldol-type Reaction in Water or Alchol

用碱土金属试剂Ca（OH）_2、Ba（OH）_2、CaCl_2/KOH或BaCl_2/KOH代替碱金属试剂NaOH、KOH、LiCl/KOH或NaCl/KOH，在甲醇中完成了2，4-二羟基苯甲酸甲酯酚烯醇盐（1）与醛的Aldol型反应，在苯甲酸酯（1）的C（3）位上区域选择性地进行了C-C键的形成。在CaCl_2/KOH的甲醇溶液中，1，3-二羟基丙酮（2）与甲醛反应，在不保护羟基的情况下，甲醛与2发生羟醛缩合反应，生成甘油四果糖（3）和3-戊酮糖（4）。相反，在水中进行的该反应主要得到1-羟基-2，3-丁二酮（5）。5的形成意味着3的脱水在水中被加速。在水溶液中使用胺作为碱性催化剂也促进了3的脱水得到5。上述顺序成功地应用于由甘油四果糖（3）和甲醛立体选择性合成苏式-4。SmCl_3和KOH的组合具有较高的苏式选择性，与可溶于水的（CH_2O）_n相比，我们选择了一种疏水醛苯甲醛，它的水合形式比例较低。1，3-二羟基丙酮（2）易溶于水，容易形成环状二聚体，其中含有半缩醛基团而不是羰基。因此，当2和苯甲醛在甲醇中用Ca（OH）_2或CaCl_2/KOH处理时，2的烯醇化物不是与另一个二羟基丙酮分子反应，而是与苯甲醛反应，生成富含苏式的4-C-苯基甘油四果糖。在2与甲基乙烯基酮反应的情况下，4-乙酰基-2，3，4，5-四氢-3-羟基-3-（羟甲基）呋喃通过杂1，4-加成反应，然后分子内羟醛型环化产生。

The aldol type reaction of phenolic enolate of methyl 2,4-dihydroxybenzoate (1) with aldehydes in methanol was accomplishied using alkaline earth metal reagents such as Ca (OH) _2, Ba (OH) _2, CaCl_2/KOH,or BaCl_2/KOH instead of alkaline metal reagents such as NaOH,KOH,LiCl/KOH or NaCl/KOH.The C-C bond formation was regioselectively performaed at the C (3) position of benzoate 1. When the reaction of 1,3-dihydroxyacetone (2) with formaldehyde was promoted by CaCl_2/KOH in methanol, the aldolcondensation between formaldehyde and 2 without protection of the hydroxy groups gave glycerotetrulose (3) and 3-pentulose (4). In contrast, this reaction carried out in water mainly gave 1-hydroxy-2,3-butanedione (5). Formation of 5 means that the dehydration of 3 is accelerated in water. Utilization of amines as a basic catalyst in water also promoted the dehydration of 3 to afford 5.The sequence described above was successfully applied to the stereoselective synthesis of threo-4 from glycero-tetrulose (3) and formaldehyde. Combination of SmCl_3 with KOH perfomed this *nsformation with the higher threo selectivity.In comparison with (CH_2O) _n which is soluble in water, we chose a hydrophobic aldehyde, benzaldehyde, whose proportion of the hydrate form is low. 1,3-Dihydroxyacetone (2) is soluble in water and easily form cyclic dimers which contain hemiacetal groups in stead of the carbonyl group. Therefore, when 2 and benzaldehyde were treated with Ca (OH) _2 or CaCl_2/KOH in methanol, the enolate of 2 reacted not with another dihydroxyacetone molecule but with benzaldehyde to yield threo-rich 4-C-phenyl glycero-tetrulose. In the case of the reaction of 2 with methyl vinyl ketone, 4-acetyl-2,3,4,5-tetrahydro-3-hydroxy-3- (hydroxymethyl) furan was produced by the hetero 1,4-addition reaction followed by intramolecular aldol-type cyclization.