[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.

Ring Forming Reactions.

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

Copper Isocyanide Mediated Annulation with a,b-Unsaturated Esters.

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).

Reaction with Heteroatom Nucleophiles.

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

1. Danieli, B.; Lesma, G.; Palmisano, G. CC 1980, 860.
2. Hua, D. H.; Bharathi, S. N.; Robinson, P. D.; Tsujimoto, A. JOC 1990, 55, 2128.
3. Ogura, K.; Ishida, M.; Tomori, H.; Fujita, M. BCJ 1989, 62, 3531.
4. Chou, T. S.; Chang, L. A.; Tso, H. H. JCS(P1) 1986, 1039.
5. Tso, H. H.; Chou, T. S.; Lee, W. C. CC 1987, 934.
6. Saegusa, T.; Ito, Y. S 1975, 291.
7. Ito, Y.; Nakayama, K.; Yonezawa, K.; Saegusa, T. JOC 1974, 39, 3273.
8. Carlier, P. R.; Sharpless, K. B. JOC 1989, 54, 4016.
9. Soai, K.; Nishi, M.; Ito, Y. CL 1987, 2405.

Yoshihiko Ito & Michinori Suginome

Kyoto University, Japan

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