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A New Synthesis of Benzylidene Acetals
Author(s) -
Li Chunbao,
Vasella Andrea
Publication year - 1993
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19930760115
Subject(s) - chemistry , diazirine , moiety , diol , regioselectivity , medicinal chemistry , protonation , diastereomer , alkoxy group , acetal , enol , stereochemistry , conformational isomerism , aryl , thermal decomposition , organic chemistry , ion , catalysis , molecule , alkyl
Aryl‐halo‐diazirines react under basic conditions with 1,3‐ cis ‐, 1,2‐ cis and 1,2‐ trans ‐diols to give acetals. Yields are high. Diastereoselectivities depend upon the diol and upon the reaction conditions. Thus, reaction of the 1,3‐ cis ‐diol 1 ( Scheme 1 ) with 2 gave 3 as a single diastereoisomer. The 1,2‐ cis ‐diols 4 and 7 led to the endo ‐ and exo ‐acetals 5 / 6 (93:7) and 8 / 9 ( ca .10:1), respectively, The 1,2‐ trans ‐diols 10 , 16 , and 19 reacted with 2 to afford 11 / 12 (90:10), 17 / 18 (1:1), and 20 / 21 (6:1), respectively. Reaction of the (4‐nitrophenyl)diazirine 13 with 10 at higher temperatures yielded 14 / 15 (6:4). The uracil moiety, the acetamido group, and the enol‐ether moiety are compatible with the reaction conditions. The diastereoselectivity is rationalized on the basis of a reaction sequence involving alkoxy‐halogen exchange, which is regioselective or not, thermolysis of the ensuing alkoxydiazirine(s), protonation of the alkoxycarbene to form an ( E )‐configurated oxycarbenium ion, and attack of the neighboring oxy or hydroxy group, which is only possible for a limited range of conformers.