Regioselective synthesis of furan-fused 3-hydroxy-2,2-dimethylchroman, NG-121 model compound

Synlett

Volumn , Issue 9, 2006, Pages 1363-1366

  Inoue, Seiichi ^a   Nakagawa, Chihiro ^a   Hayakawa, Hidetaka ^a   Iwasaki, Fumiyoshi ^a   Hoshino, Yujiro ^a   Honda, Kiyoshi ^a  

^a YOKOHAMA NATIONAL UNIVERSITY   (Japan)

Author keywords

Lactones; Phenols; Regioselective formylation; Sigmatropic rearrangement; Ylides

Indexed keywords

3 HYDROXY 2,2 DIMETHYLCHROMAN; CHROMAN DERIVATIVE; LACTONE DERIVATIVE; NG 121; PHENOL; PROBIOTIC AGENT; SULFUR DERIVATIVE; UNCLASSIFIED DRUG;

ALKYLATION; ARTICLE; DEUTERON NUCLEAR MAGNETIC RESONANCE; DRUG SYNTHESIS; STACHYBOTRYS;

EID: 33745331217     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2006-941561     Document Type: Article

References (19)

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10. Inoue, S.; Asami, M.; Honda, K.; Shrestha, K. S.; Takahashi, T.; Yoshino, T. Synlett 1998, 679.
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12. Weinreb, S. M. Synth. Commun. 1982, 989.
13. The sulfide 9 was synthesized from commercially available 2-methyl-3-buten-2-ol according to the previously reported procedure, see ref. 4.
14. 13C COSY, and DEPT spectroscopy. It was impossible to determine the relative configuration of 11a, 12a, 13a, and 14a.
15. In support of the assigned regiochemistry for 11a and 12a, a strong NOESY correlation was observed between the signals for the methoxy group and the C-6 proton of the aromatic ring. On the other hand, for 13a and 14a, a strong NOESY correlation was observed between the signals for the methoxy group and the C-4 and C-6 protons of the aromatic ring.
16. Amides 11b, 12b, 13b, and 14b were also isolated by column chromatography on silica gel.
17. The [2,3]sigmatropic rearrangement of 3-hydroxy-5-methoxy-N,N- diisopropylbenzamide and a higher terpenyl sulfide, prepared from geraniol according to a method similar to the synthesis of 9, afforded the para-alkylated benzamide and the ortho-alkylated isomer in a 2:1 ratio. Similar alkylation of 3-hydroxy-5-methoxy-N,N-dibutylbenzamide 3b afforded the para-alkylated benzamide and the ortho-alkylated isomer in a 3:1 ratio and alkylation of 3-hydroxy-5-methoxy-N,N-dihexylbenzamide also afforded the para-alkylated benzamide and the ortho-alkylated isomer in a 3:1 ratio.
18. 4 the terpenyl sulfide was reacted with 3b to give the para-alkylated benzamide and the ortho-alkylated isomer in a 3:1 ratio. The para-alkylated benzamide was converted to the corresponding 3-hydroxy-2,2-dialkylchroman according to a similar synthetic route to that shown in Scheme 4. The chroman compound was regioselectively formylated in 58% yield.
19. 3): δ = 171.8, 159.5, 147.9, 127.6, 125.2, 114.5, 97.14, 77.59, 68.64, 68.09, 55.90, 26.97, 24.58, 22.03.