Tricarbonyl[(2,3,4,5,6,7-h)-thiepin-1,1-dioxide]chromium(0)1

[1452247-44-5]  · C9H6CrO5S  · (278.201)

(reagent used for promotion of [6+2], [6+4], [6+2+2], and [6+2+2+2] higher-order cycloaddition reactions)

Physical Data: red solid; mp 173-174°C.

Solubility: THF, ethyl acetate, CH2Cl2, CHCl3, and 1,2-dichloroethane.

Form Supplied in: prepared from thiepin-1,1-dioxide and trisacetonitriletricarbonylchromium.

Purification: flash column chromatography on silica gel using hexanes/ethyl acetate.

Handling, Storage, and Precautions: the compound can be handled in air and is generally stable for several months when stored in the freezer.

Preparative Methods: as shown below, thiepin chromium complex 1 is readily prepared via standard methods1 from thiepin-1,1-dioxide2 2 and trisacetonitriletricarbonylchromium(0)3 3. The reaction proceeds in 12 h at room temperature to give an 86% yield of the desired chromium complex 1 (eq 1).4

[6+2] Higher-Order Cycloaddition Reactions.

Chromium complex 1 undergoes a variety of higher-order cycloaddition reactions.5 Thus, a reaction between complex 1 and disubstituted alkyne partners in the presence of UV light (uranium filter) produces [6p+2p] cycloadducts in good yields (eq 3, Table 1). Cyclooctyne (entry 5, Table 1) notably provides an 80% yield of the cycloadduct.6

Surprisingly, unlike the tricarbonylcycloheptatriene chromium(0), complex 1 does not react with alkenes to give [6p+2p] cycloadducts.7

[6+2+2] Higher-Order Cycloaddition Reactions.

Rigby and coworkers have advanced the field of multicomponent cycloaddition reactions using thiepin chromium complex 1 and terminal alkynes.8 The reaction proceeds via a process that can be viewed formally as two consecutive [6p+2p] cycloaddition events to give tetracycle 5 (eq 3). The cycloaddition events occur in the coordination sphere of the chromium, thus the reaction sets the six new stereogenic centers in tetracycle 5 stereospecifically, and only one diastereomer is observed.9

Examples of the [6+2+2] reaction are included in Table 2.8a The reaction requires either photochemical (entries 1-3) or thermal (entry 4) conditions to provide tetracycles5.

Furthermore, the 2 components can be tethered together so the new product will have one additional ring. Thus, diyne 6 is slowly added over 2 h to a solution of complex 1 in a photochemical reactor to provide a 57% yield of pentacycle 8. Likewise, slow addition of diyne 7 gives pentacycle 9 in a diminished yield, presumably due to competitive polymerization (eq 5).10

[6+2+2+2] Higher-Order Cycloaddition Reactions.

Recently, Rigby and coworkers observed another product during their studies on the three component cycloaddition reactions using tethered alkynes. Thus, a photochemically promoted reaction between thiepin chromium complex 1 and excess octa-1,7-diyne 10 gave pentacycle 12 in 45% yield. Likewise, nonadiene 11 provided pentacycle 13 in 38% yield (eq 6).11

The mechanism leading to pentacycles 12 and 13 has not been established; however, the reaction may proceed via two sequential [6p+2p] cycloaddition reactions followed by a what appears to be a [3+2] cycloaddition. If the final step involves a [3+2] cycloaddition reaction, then these examples would represent the first examples of a chromium-mediated [3+2] cycloaddition reaction.11

[6+4] Higher-Order Cycloaddition Reactions.

By far, the most extensively investigated reaction of chromium complex 1 is the [6+4] cycloaddition reaction.4,7a,12 The reaction between complex 1 and several dienes was examined, and it was determined that electron-rich 4 partners provided much higher yields than those of electron deficient partners. Thus, diene 14 reacts with chromium complex 1 under photochemical conditions to give an excellent yield of cycloadduct 15, whereas, diene 16 gives a 38% yield of the corresponding cycloadduct 17 (eq 7).12b

Other more complex dienes have also been examined in this reaction and are listed below (eq 8-11).7,13

The [6p+4p] cycloaddition reaction can also be promoted thermally. For example, a tert-butylmethylether solution of chromium complex 1 and diene 14 was heated to reflux (110°C) for 48 h. Upon isolation via column chromatography on silica gel, compound 15 was again obtained but with a diminished yield (47%) (eq 12).12b

Sulfur Dioxide Extrusion and Applications Toward Total Synthesis.

The sulfur-containing products, which result from the higher-order cycloaddition reactions described above, have been submitted to various conditions to extrude the elements of sulfur dioxide. For example, photolysis (quartz filter) of cycloadduct 15 for 15 min promotes a cheletropic extrusion of sulfur dioxide to give a 54% yield of cyclodecatetraene 26 (eq 13).4

A very different sulfur dioxide extrusion protocol has been applied to the total synthesis of (+)-estradiol (30) by Rigby and coworkers.13 In the event, the trimethylsilyl-substituted chromium thiepin complex 27 participated in a [6p+4p] cycloaddition reaction to provide a 70% yield of the structurally complex dihydrothepin 28. Subsequent sulfur dioxide extrusion via a Ramberg-Bäcklund-type ring contraction gave tetracycle 29. The total synthesis of (+)-estradiol (30) was completed using a four-step sequence of standard reactions (eq 14).13

Related Reagents.

tricarbonyl[(2,3,4,5,6,7-h)-cyclo-heptatriene]chromium(0);1 tricarbonyl[(2,3,4,5,6,7-h)-thiepin-1,1-dioxide]molybdenum(0);12b tricarbonyl[(2,3,4,5,6,7-h)-thiepin-1,1-dioxide]tungsten(0);12b tricarbonyl[(2,3,4,5,6,7-h)-thiepin]iron(0);14 tricarbonyl[(2,3,4,5,6,7-h)methyl-1H-azepine-1-carboxylate]chromium;4 thiepin-1,1-dioxide;2 trisaceto-nitriletricarbonyl-chromium(0).3


1. Rigby, J. H.; Fales, K. R., Org. Syn. 1999, 77, 121.
2. (a) Mock, W. L., J. Am. Chem. Soc. 1967, 89, 1281. (b) Mock, W. L.; McCausland, J. H., J. Org. Chem. 1976, 41, 242.
3. Tate, D. P.; Knipple, W. R.; Augl, J. M., Inorganic Chem. 1962, 1, 433.
4. Rigby, J. H.; Ateeq, H. S.; Krueger, A. C., Tetrahedron Lett. 1992, 33, 5873.
5. For reviews on higher-order cycloaddition chemistry, see: (a) Hosomi, A.; Tominaga, Y. In Comprehensive Organic Synthesis; Trost, B. M.; Fleming, I., Eds.; Pergamon Press: Oxford; 1991, Vol. 5, pp 593-615. (b) Rigby, J. H. In Comprehensive Organic Synthesis; Trost, B. M.; Fleming, I., Eds.; Pergamon Press: Oxford; 1991, Vol. 5, pp 617-643. (c) Wender, P. A.; Siggel, L.; Nuss, J. M. In Comprehensive Organic Synthesis; Trost, B. M.; Fleming, I., Eds.; Pergamon Press: Oxford; 1991, Vol. 5, pp 645-673.
6. Rigby, J. H.; Warshakoon, N. C., Tetrahedron Lett. 1997, 38, 2049.
7. (a) Rigby, J. H., Tetrahedron 1999, 55, 4521. (b) Warshakoon, N. C., Ph.D. Dissertation, Wayne State University, 1998.
8. (a) Rigby, J. H.; Warshakoon, N. C.; Heeg, M. J., J. Am. Chem. Soc. 1996, 118, 6094. (b) For a review on metal promoted cycloaddition reactions, see: Lautens, M.; Klute, W.; Tam, W., Chem. Rev. 1996, 96, 49.
9. An iron(0)-mediated process between cycloheptatriene and and alkyne resulting in a [6+2+2]-type product was first reported by: Goddard, R.; Woodward, P., J. Chem. Soc., Dalton Trans. 1979, 711.
10. Rigby, J. H.; Heap Charles, R.; Warshakoon, N. C., Tetrahedron 2000, 56, 2305.
11. Rigby, J. H.; Heap Charles, R.; Warshakoon, N. C.; Heeg, M. J., Org. Lett. 1999, 1, 507-508.
12. (a) Rigby, J. H.; Warshakoon, N. C., J. Org. Chem. 1996, 61, 7644. (b) Rigby, J. H.; Ateeq, H. S.; Charles, N. R.; Cuisiat, S. V.; Ferguson, M D.; Henshilwood, J. A.; Krueger, A. C.; Ogbu, C. O.; Short, K. M.; Heeg, M. J., J. Am. Chem. Soc. 1993, 115, 1382.
13. Rigby, J. H.; Warshakoon, N. C.; Payen, A. J., J. Am. Chem. Soc. 1999, 121, 8237.
14. Nishino, K.; Tagagi, M.; Kawata, T.; Murata, I.; Inanaga, J.; Nakasuji, K., J. Am. Chem. Soc. 1991, 113, 5059.

Brian J. Myers

Wayne State University, Detroit, MI, USA



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