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

2，4-二羟基苯甲酸甲酯(1)在甲醇中用碱土金属试剂Ca(OH)_2、Ba(OH)_2、CaCl2/KOH或BaCl2/KOH代替碱金属试剂NaOH、KOH、LiCl/KOH或NaC/KOH，在甲醇中实现了2，4-二羟基苯甲酸甲酯(1)与醛的Aldol型反应。在甲醇中，当Cl2/KOH促进1，3-二羟基丙酮(2)与甲醛的反应时，甲醛和2在没有羟基保护的情况下发生缩醛反应，得到甘油四糖(3)和3-戊果糖(4)。相反，该反应在水中进行，主要生成1-羟基-2，3-丁二酮(5)。5的形成意味着3在水中的脱水被加速。在水中使用胺作为碱性催化剂，也促进了3脱水生成5。上述序列被成功地应用于四聚甘油(3)和甲醛的立体选择性合成苏氨酸-4。SmCl3与KOH的结合使该反应具有较高的苏基选择性，与可溶于水的(CH2O)n相比，我们选择了水合物比例较低的疏水醛苯甲醛。1，3-二羟基丙酮(2)溶于水，容易形成含有半缩醛基团的环状二聚体，而不是羰基。因此，当2和苯甲醛在甲醇中用Ca(OH)2或CaCl2/KOH反应时，2的烯醇酸酯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氨酸的4-C-苯基甘油四丁糖。在2与甲基乙烯基酮的反应中，通过杂1，4加成反应和分子内Aldol环化反应合成了4-乙酰基-2，3，4，5-四氢-3-羟基-3-羟甲基呋喃。

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.