Cerium(III) Chloride-Tin(II) Chloride

 · CeCl3  · Cerium(III) Chloride-Tin(II) Chloride  · Cl2Sn  · Cerium(III) Chloride-Tin(II) Chloride

(combined reagent; reduces a-bromo ketones to yield cerium enolates which undergo cross-aldol reaction; reduces a,a-dibromo ketones to yield oxyallyl cations which undergo [3 + 4] cycloaddition with 1,3-dienes)

Physical Data: see Cerium(III) Chloride and Tin(II) Chloride.

Aldol Reactions with a-Bromo Ketones.1

The combination of cerium(III) trichloride-tin(II) chloride in conjunction with a-bromo ketones and carbonyl compounds in THF affords b-hydroxy ketones in good to excellent yields after aqueous workup (eq 1).

Carbon-carbon bond formation takes place regioselectively at the site of the bromine atom. Thus the reaction of 2-bromo-2-methylcyclohexanone or 2-bromo-6-methylcyclohexanone with benzaldehyde affords the corresponding b-hydroxy ketone without any contamination of the regioisomer (eq 2). This result indicates that no retro-aldol or cross-enolization processes occur in the reaction.

Reactions with ketones provide low yields (30-40%) of the desired aldol products compared with aldehydes. The difference in reactivity between aldehydes and ketones was successfully exploited in the chemoselective aldol condensation to 6-oxoheptanal (eq 3).

The success of this strategy for cross-aldol reaction is attributed to activation of carbonyl group by Lewis acidic CeCl3 which promotes the reduction of bromine by SnCl2 (eq 4). Neither CeCl3 nor SnCl2 alone gives the coupled products. A cerium enolate intermediate is implicated in the reaction since the tin enolate generated from 2-bromocyclohexanone and low-valent tin (SnCl2/LiAlH4) reacts with benzaldehyde to afford the erythro isomer predominantly,2 while CeCl3-SnCl2 gives high threo selectivity in the same reaction (erythro:threo = 15:85-11:89) (eq 5).

Reformatsky-type reactions cannot be carried out utilizing this combination of reagents,3 and a-chloro ketones are also unreactive as cerium enolate precursors. Examples of related reagents include the organoaluminum system Et2AlCl-SnCl2.4 This combination sometimes requires a Pd0 complex, whereas the CeCl3-SnCl2 system functions effectively without palladium and is less sensitive to air and moisture contamination.

[3 + 4] Cycloadditions.5

The combined reagent CeCl3-SnCl2 promotes the [3 + 4] cycloaddition reaction of a,a-dibromo ketones with 1,3-dienes in THF effectively under mild conditions (0 °C-rt, 2 h) (eq 6). Furan and cyclopentadiene provide very good yields of the expected cycloadducts. With acyclic 1,3-dienes, 4-cyclohepten-1-ones are produced in modest yields. It is noteworthy that the reaction of 2,4-dibromo-3-pentanone with isoprene gives both [3 + 4] and [3 + 2] cycloadducts. [3 + 2] Cycloaddition proceeds similarly with enamines to afford 2-cyclopenten-1-ones after treatment with 3% ethanolic NaOH solution.

The CeCl3-SnCl2 reagent is a more convenient system for these cycloadditions compared to other procedures.6 This reaction procedure is quite simple and is carried out at room temperature in air. The reaction involves reduction of an a,a-dibromo ketone to afford an oxyallyl cation that can be captured by 1,3-dienes in the usual way.

1. Fukuzawa, S.-i.; Tsuruta, T.; Fujinami, T.; Sakai, S. JCS(P1) 1987, 1473.
2. Harada, T.; Mukaiyama, T.; CL 1982, 467.
3. Recent work has revealed that Reformatsky-type reactions could be carried out by using lithium benzenetellurorate-CeCl3. Fukuzawa, S.-i.; Hirai, K. JCS(P1) 1993, 1963.
4. Matsubara, S.; Tsuboniwa, N.; Moriszawa, Y.; Oshima, K.; Nozaki, H.; BCJ 1987, 57, 3242.
5. Fukuzawa, S.-i.; Fukushima, M.; Fujinami, T.; Sakai, S. BCJ 1989, 62, 2348.
6. (a) Hoffmann, H. M. R.; Clemens, K. E.; Schmidt, E. A.; Smithers, R. H. JACS 1972, 94, 3201; 1972, 94, 3940. (b) Noyori, R.; Hayakawa, Y. OR 1983, 29, 163. (c) Noyori, R.; Hayakawa, Y.; Tanaka, H.; Murai, S.; Kobayashi, R.; Sonoda, N. JACS 1978, 100, 1759. (d) Takaya, T.; Makino, S.; Hayakawa, Y.; Noyori, R. JACS 1978, 100, 1765. (e) Hayakawa, Y.; Yokoyama, K.; Noyori, R. JACS 1978, 100, 1791 ;1799.

Shin-ichi Fukuzawa

Chuo University, Tokyo, Japan

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