[627-31-6] · C3H6I2 · 1,3-Diiodopropane · (MW 295.89)
(electrophilic trimethylene synthon)
Physical Data: bp 111-113 °C/31 mmHg; d 2.576 g cm-3.
Form Supplied in: light brown liquid stabilized with copper.
Handling, Storage, and Precautions: light sensitive; must be stored in the dark. Use in a fume hood.
Stepwise ring closure using 1,3-diiodopropane as an electrophile is an important method for the construction of four- to six-membered rings. The ketimine (1) is converted into (2) (a pivotal intermediate for preparation of clinically useful antihypertensive eburnane alkaloids) by treatment with 1,3-diiodopropane in the presence of Diisopropylethylamine in acetonitrile under an inert atmosphere. The presence of oxygen leads to the formation of the corresponding 1-hydroxy derivative, presumably via a radical chain oxidation process initiated by iodine generated by the thermal decomposition of 1,3-diiodopropane (eq 1).1
A chiral a-sulfinyl ketimine anion undergoes annulation with 1,3-diiodopropane to give a cyclic b-sulfinyl enamine which is a precursor for various indolizidine alkaloids (eq 2).2
The a,a´-dianion generated by treatment of (p-tolylsulfinyl)acetone with 2.2 equiv of Lithium Diisopropylamide (LDA) reacts with 1,3-diiodopropane to afford the a´-substituted product (3), which is intramolecularly cyclized with LDA to give 2-(p-tolylsulfinyl)cyclohexanone (eq 3).3
Treatment of 2,5-dihydrothiophene 1,1-dioxide with 2 equiv of Lithium Hexamethyldisilazide and 1,3-diiodopropane affords the fused bicyclic sulfone (eq 4).4 On the other hand, 2-trimethylsilyl-2,5-dihydrothiophene 1,1-dioxide gives the spiro sulfone on treatment with n-Butyllithium and 1,3-diiodopropane in the presence of Hexamethylphosphoric Triamide (HMPA) (eq 5).5
1,3-Diiodopropane reacts with a,b-unsaturated esters to give cyclopentanecarboxylates in the presence of copper isocyanide (eq 6).6,7 The intermediacy of a 3-iodopropylcopper isocyanide complex is proposed; 1,3-dibromopropane and 1,3-dichloropropane give much inferior yields. Diethyl fumarate and diethyl maleate both afford trans-1,2-dicarbethoxycyclopentane, presumably because diethyl maleate is converted to diethyl fumarate prior to the cyclization and/or because cis-1,2-diethoxycarbonylcyclopentane, once formed, isomerizes to the trans isomer under the conditions (eq 7).
1,3-Diiodopropane reacts with 2 equiv of heteroatom nucleophiles, i.e. carboxylates or amines, to give trimethylene-linked dimers. For example, the ammonium salt of monobenzyl tartaric acid is alkylated by 0.5 equiv of 1,3-diiodopropane to give (4), which is used as a ligand for titanium in a complex for asymmetric epoxidation of allylic alcohols (eq 8).8 A C2 symmetric dimer of (1R,2S)-(-)-ephedrine is also prepared by alkylation with 1,3-diiodopropane and used as an asymmetric catalyst for addition of Diethylzinc to aldehydes (eq 9).9
Yoshihiko Ito & Michinori Suginome
Kyoto University, Japan