153996-36-2Relevant academic research and scientific papers
Synthesis of Monoprotected 2-Alkylidene-1,3-propanediols by an Unusual SN2' Mitsunobu Reaction
Charette, Andre B.,Cote, Bernard,Monroc, Sylvie,Prescott, Sylvie
, p. 6888 - 6894 (2007/10/03)
A simple and efficient route to monoprotected (E)- and (Z)-2-alkylidene-1,3-propanediols is described.The key step involves an unusual regio- and stereoselective SN2' Mitsunobu reaction of substituted 3-hydroxy-2-methylenealkanoates which are readily available from a Baylis-Hillman reaction between methyl acrylate and an aldehyde.These allylic alcohols, when treated with PPh3, a carboxylic acid, and DEAD in THF at temperatures ranging from -40 deg C to 22 deg C, produced the corresponding 2-alkylidene-3-hydroxypropanoate derivatives (or (E)-2-(hydroxymethyl)-3-substituted-2-alkenoate derivatives) in >70percent with SN2':SN2 ratio of 22:1 to >50:1.It was found that weak and bulky carboxylic acids and low temperatures favor SN2' addition.The reaction conditions were effective for alkyl substituted derivatives, but the addition of Et3N to the Mitsunobu conditions was necessary to improve the SN2':SN2 ratios for the vinyl 19 and phenyl 20 derivatives.The monoprotected (Z)- and (E)-2-alkylidene-1,3-propanediols can be efficiently synthesized by a three-step sequence involving either a transesterification, protection, and DIBAL-H reduction (>80percent overall yield) or by the chemoselective reduction, protection, and ester cleavage (67percent overall yield).
Synthesis of Monoprotected 2-alkylydene-1,3-Propanediols by an Unusual SN2' Mitsunobu Reaction
Charette, Andre B.,Cote, Bernard
, p. 6833 - 6836 (2007/10/02)
A simple and efficient route to monoprotected E- and Z-2-alkylidene-1,3-propanediols was developed.The key step involves an unusual regio- and stereoselective SN2' Mitsunobu reaction of substituted 3-hydroxy-2-methylenealkenoate.
