[638-37-9] · C4H6O2 · Succindialdehyde · (MW 86.10)
(useful annulating reagent for constructing heterocycles)
Alternate Name: butanedial.
Physical Data: oil, bp 62 °C/14 mmHg.
Solubility: v sol water, alcohol, ether.
Preparative Methods: easily made by acidic hydrolysis of its stable, commercially available synthetic equivalent 2,5-Dimethoxytetrahydrofuran (or its diethoxy analog), followed by extraction with ether and distillation (eq 1).1
Handling, Storage, and Precautions: succindialdehyde rapidly polymerizes and has to be used immediately after distillation. Use in a fume hood.
Succindialdehyde is largely used as an annulating agent in the synthesis of pyrrole and pyrrolidine derivatives. Use of 2,5-dimethoxytetrahydrofuran as a precursor of the dialdehyde may be preferred in some instances. A familiar example is the Robinson-Schöpf cyclization (eq 2)2 (for similar reactions see also Glutaraldehyde).
Using the same methodology, 2,5-dicyanopyrrolidines can be prepared with cyanide as nucleophile (eq 3); in this example, succindialdehyde is used as its bis-sodium bisulfite adduct.3
Pyrrolidines are formed by reductive alkylation (eq 4),4 whereas in the absence of any nucleophilic reagent the double condensation of succindialdehyde with a primary amine gives a pyrrole (eq 5).5
Succindialdehyde can also be considered as a linear C4 unit useful in the synthesis of natural products. It has been used as starting material in the synthesis of squalene;6 the first step consists of the addition of a Grignard reagent to both aldehyde functions (eq 6).
The diol thus obtained can be cyclized to give a 2,5-dialkyltetrahydrofuran, as in the example (eq 7) using Mitsunobu conditions.7
Succindialdehyde has also proved useful in the synthesis of the anthracycline skeleton (eq 8) via two aldol-type reactions.8
A formal phenyl homologation can be achieved by the double aldol condensation of phthalaldehyde with succindialdehyde. In this example, succindialdehyde is generated in situ from 2,5-dimethoxytetrahydrofuran (eq 9).9
Université René Descartes, Paris, France
CNRS, Gif-sur-Yvette, France