Metals are widely used in organic chemistry to perform synthetic transformations. Generally, the main problem associated with organometallic species is the high sensitivity to air and moisture. Inert atmosphere and dry solvents are usually required to perform organometallic reactions successfully.

Starting in the 1970s, indium became of interest for organometallic transformations. The first reported use of indium in organic synthesis was in 1975 by Rieke and co-workers.¹ They used indium for a metal mediated Reformatsky type reaction between an a -halocarbonyl compound and a variety of aldehydes and ketones. Later on, Butsugan and co-workers² also performed Reformatsky reactions with indium (Scheme 1).

Butsugan’s group also investigated the use of indium for allylation reactions.³ A variety of aldehydes and ketones would react with several allyl halides using indium in DMF with excellent yields (Scheme 2).

However, this indium mediated allylation reaction did not become of interest for the organic chemist until Chan and co-workers demonstrated the attractiveness of allylindium additions to carbonyl compounds performed in water.⁴ No inert atmosphere or dry solvents are required to perform allyl indium additions (Scheme 3).

Within this context, a lot of methodological studies have focused on the chemistry of indium with organic molecules in water for the past several years. Issues such as chemoselectivity, regioselectivity and diastereoselectivity have been extensively investigated.^5,6 The most intriguing result from these studies is the use of free hydroxyl groups to direct the allyl additions to carbonyl compounds (Scheme 4).

The possibility of avoiding extra protection-deprotection steps for the hydroxyl groups and obtaining a high diastereoselectivity has attracted the synthetic organic chemists. Most of the examples in which allylindium additions are applied to the synthesis of natural products are in carbohydrate chemistry. Chain elongation, synthesis of deoxysugars, and synthesis of carbohydrate derived natural products can be performed much more efficiently since the tedious hydroxyl protection-deprotection chemistry can be avoided. An important class of compounds synthesized with this methodology is the sialic acids family. Starting from D-mannose, the corresponding sialic acid can be synthesized in two steps (Scheme 5).⁷

In addition to the use of allyl indium species, some studies have been carried out on propargyl indium species. Although much less is known about propargyl indium additions to carbonyl compounds, some preliminary results showed very good regioselectivity on such additions (Scheme 6).⁸

This methodology has also been proven to be useful on the total synthesis of (+)-goniofufurone, an antitumor agent isolated from the asian tree Goniothalamus (Scheme 7).⁹

Some methodology studies on indium as well as some of the most important synthetic applications involving an indium mediated reaction as the key step will be presented.

1. Rieke, R. D.; Chao, L. C. J. Org. Chem. 1975, 40, 2253-3355.
2. Araki, S.; Butsugan, Y. J. Org. Chem. 1988, 53, 1831-1833.
3. Araki, S.; Katsamura, N.; Kawasaki, K.; Butsugan, Y. J. Chem. Soc., Perkin Trans. 1 1991, 53, 499-504.
4. Chan, T. H.; Li, C. J. Tetrahedron Lett. 1991, 32, 7017-7020.
5. Chan, T. H.; Isaak, M. B. Tetrahedron Lett. 1995, 36, 8957-8960.
6. Paquette, L. A.; Mitzel, T. H. J. Am. Chem. Soc. 1996, 118, 1931-1937.
7. Chan, T. H.; Lee, M. C. J. Org. Chem. 1995, 60, 4228-4232.
8. Isaak, M. V.; Chan, T. H. J. Chem. Soc., Chem. Commun. 1995, 1003-1006.
9. Yi, X. H.; Meng Y.; Hua X. G.; Li, C. J. J. Org. Chem. 1998, 63, 7472-7480.

1. Cintas, P. Synlett 1995, 1089-1096.
2. Li, C. J. Tetrahedron 1996, 52, 5643-5668.
3. Marshall, J. A. Chemtracts, Org. Chem. 1997, 10, 481-496.
4. Li, C. J. in Green Chemistry, Frontiers in Benign Chemical Syntheses and Processes, Eds. Anastas, P. and Williamson, T. C. Oxford University Press, New York, 1998 (Chapter 14).
5. Paquette, L. A. in Green Chemistry, Frontiers in Benign Chemical Syntheses and Processes, Eds. Anastas, P. and Williamson, T. C. Oxford University Press, New York, 1998 (Chapter 15).
6. Li, C. J.; Chan, T. K. Tetrahedron, 1999, 55, 11149-11176.