ACYCLIC STEREOSELECTION .53. PROTOCOLS FOR THE PREPARATION OF EACH OF THE 4 POSSIBLE STEREOISOMERIC ALPHA-ALKYL-BETA-HYDROXY CARBOXYLIC-ACIDS FROM A SINGLE CHIRAL ALDOL REAGENT
ACYCLIC STEREOSELECTION .53. PROTOCOLS FOR THE PREPARATION OF EACH OF THE 4 POSSIBLE STEREOISOMERIC ALPHA-ALKYL-BETA-HYDROXY CARBOXYLIC-ACIDS FROM A SINGLE CHIRAL ALDOL REAGENT
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DOI：
10.1021/jo00007a043
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发表时间：
1991-03-29
影响因子：
3.6
通讯作者：
HEATHCOCK, CH
中科院分区：
文献类型：
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作者：
VANDRAANEN, NA;ARSENIYADIS, S;HEATHCOCK, CH
已经设计了方案，其中所有四种可能的立体异构α-烷基-β-羟基羧酸可以衍生自单一的羟醛试剂，羟基酮3。 化合物3以对映异构体均相形式以50%总产率从叔丁基甘氨酸（1）获得，以其三甲基甲硅烷基和叔丁基二甲基甲硅烷基衍生物4和5的形式用于羟醛缩合反应。 4的Z锂烯醇化物和Z硼烯醇化物与各种醛反应，分别得到醛醇8和9。 4被溴镁2，2，6，6-四甲基哌啶（MTMP）脱质子得到E烯醇化物，其可以被三甲基氯硅烷捕获以得到E硅烷基烯醇醚11。 4的E溴镁烯醇化物与醛反应，得到结构15的醛醇。 酮醚5的烯醇化溴镁的金属转移通过与（三异丙氧基）氯化钛反应来完成。 所得E（三异丙氧基）钛烯醇化物与醛反应以提供结构17的醛醇。 由上述反应得到的醛醇水解成酮二醇19-22，其被氧化成立体异构的α-甲基-β-羟基羧酸23-26。
Protocols have been devised whereby all four possible stereoisomeric alpha-alkyl-beta-hydroxy carboxylic acids can be derived from a single aldol reagent, hydroxy ketone 3. Compound 3, obtained in enantiomerically homogeneous form in 50% overall yield from tert-butylglycine (1), is used for aldol reactions in the form of its trimethylsilyl and tert-butyldimethylsilyl derivatives, 4 and 5. The Z lithium and Z boron enolates of 4 react with various aldehydes to give aldols 8 and 9, respectively. Deprotonation of 4 by bromomagnesium 2,2,6,6-tetramethylpiperidide (MTMP) gives the E enolate, which may be trapped by trimethylsilyl chloride to obtain the E silyl enol ether 11. The E bromomagnesium enolate of 4 reacts with aldehydes to give aldols of structure 15. Transmetalation of the bromomagnesium enolate of keto ether 5 is accomplished by reaction with (triisopropoxy)titanium chloride. The resulting E (triisopropoxy)titanium enolate reacts with aldehydes to provide aldols of structure 17. The aldols resulting from the foregoing reactions are hydrolyzed to keto diols 19-22, which are oxidized to the stereoisomeric alpha-methyl-beta-hydroxy carboxylic acids 23-26.