SYNTHESIS OF ASYMMETRICALLY DEUTERATED GLYCEROL AND DIBENZYLGLYCERALDEHYDE VIA BORONIC ESTERS
SYNTHESIS OF ASYMMETRICALLY DEUTERATED GLYCEROL AND DIBENZYLGLYCERALDEHYDE VIA BORONIC ESTERS
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DOI：
10.1021/ja00166a037
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发表时间：
1990-05-09
影响因子：
15
通讯作者：
SOUNDARARAJAN, R
中科院分区：
文献类型：
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作者：
MATTESON, DS;KANDIL, AA;SOUNDARARAJAN, R
(S)-品二醇[(苄氧基)甲基]硼酸酯(1a)经改进得到(S)-品二醇(1R)-[1，2-二(苄氧基)乙基]硼酸酯(3a)(96%de)，与(二溴甲基)锂反应生成(S)-品二醇(1S，2S)-[2，3-(benzyloxy)-1-bromopropyl]boronate(4DA)。用三异丙氧基硼氢化钾处理得到了(S)-Pinandiol(1R，2R)-[2，3-bis(benzyloxy)propyl]boronate-1-d(5DA)，该化合物经过氧化氢脱溴和脱苄反应得到(1S，2S)-甘油-1-d(7D)。92-94%。(1R，2S)-甘油-1-d(7L)与(二溴甲基)锂-d反应得到(1R，2S)-甘油-1-d(7L)，再用三乙基硼氢化锂还原得到(S)-Pinandiol(1S，2R)-[2，3-bis(benzyloxy)propyl]boronate-1-d(5LA)。(S)-(对甲氧基苯基)硼二醇(1b)通过醇6b扩链，苄基化为8b，甲氧基苄基的DDQ裂解生成醇8c，然后经Swern氧化得到二苄基-(2R，3S)-甘油醛-3-d(9D)和二苄基-(2R，3R)-甘油醛-3-d(9L)。将8c转化为结晶三叔丁基醚8d的结果表明，氚标记的位置是绝对构型过剩的98%，而甘油-d的主要非对映异构体污染物(2-3%)在C(2)上是错误的。
(S)-Pinanediol [(benzyloxy)methyl]boronate (1a) has been converted via an improved procedure to (S)-pinanediol (1R)-[1,2-bis(benzyloxy)ethyl]boronate (3a) (96% de), which with (dibromomethyl)lithium has yielded (S)-pinanediol (1S,2S)-[2,3-(benzyloxy)-1-bromopropyl]boronate (4Da). Treatment with potassium triisopropoxyborodeuteride has yielded (S)-pinanediol (1R,2R)-[2,3-bis(benzyloxy)propyl]boronate-1-d (5Da), which on deboronation with hydrogen peroxide and debenzylation has yielded (1S,2S)-glycerol-1-d (7D) in .apprx. 92-94% de. The opposite diastereomer, (1R,2S)-glycerol-1-d (7L), was obtained via 3a with (dibromomethyl)lithium-d and reduction of the resulting (S)-pinanediol (1S,2R)-[2,3-bis(benzyloxy)propyl]boronate-1-d (5La) with lithium triethylborohydride. Chain extension of (S)-pinanediol (p-methoxybenzyl)boronate (1b) via the alcohols 6b, benzylation to 8b, and DDQ cleavage of the methoxybenzyl group to form alcohols 8c followed by Swern oxidation has led to dibenzyl-(2R,3S)-glyceraldehyde-3-d (9D) and dibenzyl-(2R,3R)-glyceraldehyde-3-d (9L). Conversion of 8c to the crystalline trityl ether 8d reveals that deuterium label placement is in .gtoreq.98% absolute configurational excess, and the major diastereomeric contaminant (2-3%) of the glycerol-d is in error at C(2).