A GENERAL-APPROACH TO 5-SUBSTITUTION OF 3-FURALDEHYDES

被引:28
作者
LEE, GCM
HOLMES, JM
HARCOURT, DA
GARST, ME
机构
[1] Chemical Sciences, Allergan Inc., Irvine, California 92715
关键词
D O I
10.1021/jo00037a032
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Herein we report the details of the conversion of 3-furaldehyde into 2-substituted 4-furaldehydes and the transformations of 2-substituted 4-furaldehydes and 4-substituted 3-furaldehydes into tri- and tetrasubstituted furans. We have developed a new disubstituted furan synthesis by applying metalation to the direct conversion of 3-substituted furans into 2,4-disubstituted furans. In situ protection of 3-furaldehyde with lithium morpholide followed by metalation at the C-5 position and quenching with several electrophiles affords 2-substituted 4-furaldehydes in 30-70% yield. The electrophiles include chlorosilanes, chlorostannanes, aldehydes, ketones, and primary iodides. This work provides a general route to a previously relatively inaccessible furan substitution pattern and is the first example of selective metalation at the C-5 position of 3-substituted furans. Other bulky a-alkoxy substituents at C-3 direct remote metalation to C-5 of furan. We examined other 3-furaldehyde metalations. The amino alkoxide intermediate derived from lithio N,N,N'-trimethylethylenediamine and 3-furaldehyde, when treated with BuLi and electrophiles, provided a product mixture which included metalation at the C-4 position of 3-furaldehyde. Several approaches to enhance this unusual C-4 metalation were unsuccessful. Using this amino alkoxide-metalation chemistry, 4-alkyl- or 4-phenyl-3-furaldehyde could be substituted at C-2 or C-5 selectively. Finally we converted trisubstituted furans into tetrasubstituted furans with metalation/electrophilic trapping.
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页码:3126 / 3131
页数:6
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