Chemistry Reference
In-Depth Information
tion of these heterocycles can be rationalized in terms of ring-enlargement of in-
termediate cyclopropyl aldehydes giving 2,5-dihydrooxepines by [3,3]sigmatropic
rearrangement, or dihydrofurans through a stabilized 1,3-zwitterion.
In the preparation of trifluoromethyl retinoid analogues 1837 as anticancer
agents [1328], a key intermediate, 3-trifluoromethylpropenal 1836 was synthesized
by Swern oxidation of the corresponding alcohol 1835.
R
1
Me
Me
Me
CF
3
(COCl)
2
-DMSO
F
3
C
OH
F
3
C
O
R
2
Me
1837
1835
1836
R1 = H, lower alkyl; R2 = H, CO2H, CH2OH, CHO,
fluoroalkyl, lower alkyl or alkoxycarbonyl
A facile, preparative-scale synthesis of (2R,4E )-2-methyl-4-hexenal 1841, a key in-
termediate in the synthesis of (2S,3R,4R,6E )-3-hydroxy-4-methyl-2-methylamino-6-
octenoic acid (MeBmt), has been reported [1337]. The hexenal 1841 was prepared
by hydrolyzing the starting amide 1838 with sulfuric acid, reducing the resulting
acid 1839 with LiAlH
4
, and oxidizing the resulting alcohol 1840 under the Swern
conditions.
O
O
Ph
H
3N H
2
SO
4
Me
N
H
CH
2
OH
Me
OH
Dioxane
Me
Me
1839
1838
LiAlH
4
Me
OH
Me
1840
(COCl)
2
-DMSO
Me
O
Me
1841
The novel statine analogue 1844 has been synthesized from PhCH
2
O
2
C-l-Asp-OH
in several steps. Key steps were the Swern oxidation of amino alcohol 1842 to the
aldehyde 1843 followed by an aldol condensation with LiCH
2
CO
2
Et to give a mix-
ture of 1844 and its (3R,4S)-diastereomer. The latter were hydrolyzed and then
condensed with (S)-H
2
NCH
2
CHMeEt 1845 in the presence of DCC to give amide
1846 and its (3R,4S)-diastereomer, which were separated by column chromatogra-
phy on silica gel [1329].
