3-Acetoxy-2-trimethylsilylmethyl-1-propene1

[72047-94-0]  · C9H18O2Si  · 3-Acetoxy-2-trimethylsilylmethyl-1-propene  · (MW 186.33)

(precursor for palladium trimethylenemethane cycloaddition reactions)

Physical Data: bp 68-70 °C/6.5 mmHg;2 60-61 °C/2.5 mmHg.3

Solubility: sol most organic solvents.

Preparative Methods: commercially available but expensive. Several preparations of (1)2-4 or the precursor alcohol (2)5,6 have been reported. The simplest involves the direct silylation of methallyl alcohol (eq 1).4,5

Handling, Storage, and Precautions: volatile, irritant, flammable.

Introduction.

The development by Trost and co-workers of palladium-trimethylenemethane (TMM) cycloadditions employing the title reagent (1) and related reagents was a seminal advance in ring-construction methodology. The generality and versatility of these reactions is illustrated below by their use in [3 + 2] cycloadditions to form both cyclopentanes and heterocycles, [3 + 4] and [3 + 6] cycloadditions, and applications in total synthesis.

Methylenecyclopentanes.

Many lines of evidence indicate that in the presence of catalytic Pd0, (1) forms the reactive intermediate palladium-TMM complex (3).7-9 This complex appears to be zwitterionic in character, but its reactivity is governed mainly by its nucleophilicity/basicity. Thus the TMM reactions work best and almost exclusively with electron-deficient alkenes. It appears that in most cases the cycloaddition is stepwise, with the initial Michael-like reaction followed by nucleophilic attack on a cationic p-allylpalladium complex (eq 2). The ion-pair nature of the intermediate (4) is thought to be the source of some unusual stereochemical effects which give the reactions some of the characteristics of concerted cycloadditions.10,11

The corresponding methylenecyclopentanes are readily formed from a wide variety of activated alkenes, such as unsaturated esters, lactones, and nitriles, enones, vinyl sulfones, and nitroalkenes.4 The breadth of utility of this reaction is exemplified below by its use as key steps in syntheses of albene (eq 3),12 brefeldin A (eq 4),13 hirsutene (eq 5),14 the core spirocarbocyclic rings of the ginkgolides (eq 6),15 cephalotaxine (eq 7),16 and kempanes (eq 8).17 The use of doubly activated alkenes, as in eq 8, is of particular advantage in the annulation of 2-cycloalkenones.17b

The adducts from vinyl sulfones are readily converted to cyclopentenones.18 Vinyl sulfoxides are also acceptors for Pd-TMM cycloadditions. The use of optically pure vinyl sulfoxides allows for reasonable asymmetric induction (eq 9).19 Outstanding asymmetric induction has been observed using chiral alkylideneoxazepadiones (eq 10).20

Methylenecyclopentenes.

Although Pd-TMM cycloadditions with alkynes are unsuccessful, the formation of methylenecyclopentenes from alkynes can be accomplished via the cyclopentadiene adduct (eq 11).21

Heterocycles.

Aldehydes can be converted to methylenetetrahydrofurans using tributyltin acetate or trimethyltin acetate as a cocatalyst (eq 12).22 Most ketones are completely unreactive to Pd-TMM chemistry, but some oxacyclohexanones are readily annulated (eq 13), apparently due to activation of the carbonyl by the ring oxygen(s).23 In reactions of a,b-unsaturated aldehydes and ketones, the competition between conjugate (alkene) and 1,2 (carbonyl) cycloadditions often favors reaction of the alkene. The cocatalyst Tris(acetylacetonato)indium can be used to favor the 1,2-cycloaddition.24

Methylenepyrrolidines can be formed in Pd-TMM reactions with imines (eq 14). These reactions have also been accomplished using nickel catalysts.25

[4 + 3], [6 + 3], and [3 + 3] Cycloadditions.

As suggested by the stepwise mechanism of eq 2, appropriately chosen dienes and trienes should undergo [4 + 3] and [6 + 3] cycloadditions in Pd-TMM reactions. Thus pyrones readily undergo [4 + 3] cycloadditions (eq 15),26 and tropones undergo [6 + 3] cycloadditions (eq 16).27 The main key to obtaining the higher order cycloadditions appears to be the use of all s-cis dienes and trienes.28

In a reaction that illustrates the nucleophilic character of the Pd-TMM intermediate (3), activated aziridines can undergo a [3 + 3] cycloaddition (eq 17),29 presumably via initial nucleophilic ring opening of the aziridine by the Pd-TMM.


1. Trost, B. M. AG(E) 1986, 25, 1.
2. Trost, B. M.; Buch, M.; Miller, M. L. JOC 1988, 53, 4887.
3. Agnel, G.; Malacria, M. S 1989, 687.
4. Trost, B. M.; Chan, D. M. T. JACS 1983, 105, 2315. Trost, B. M.; Chan, D. M. T. JACS 1979, 101, 6429.
5. Trost, B. M.; Chan, D. M. T.; Nanninga, T. N. OS 1984, 62, 58.
6. Knapp, S.; O'Connor, U.; Mobilio, D. TL 1980, 21, 4557.
7. Trost, B. M.; Chan, D. M. T. JACS 1979, 101, 6432.
8. Trost, B. M.; Chan, D. M. T. JACS 1980, 102, 6359.
9. Trost, B. M.; Chan, D. M. T. JACS 1983, 105, 2326.
10. Trost, B. M.; Miller, M. L. JACS 1988, 110, 3687.
11. Trost, B. M.; Mignani, S. M. TL 1986, 27, 4137.
12. Trost, B. M.; Renaut, P. JACS 1982, 104, 6668.
13. Trost, B. M.; Lynch, J.; Renaut, P.; Steinman, D. H. JACS 1986, 108, 284.
14. Cossy, J.; Belotti, D.; Pete, J. P. T 1990, 46, 1859. Cossy, J.; Belotti, D.; Pete, J. P. TL 1987, 28, 4547.
15. Trost, B. M.; Acemoglu, M. TL 1989, 30, 1495.
16. Ishibashi, H.; Okano, M.; Tamaki, H.; Maruyama, K.; Yakura, T.; Ikeda, M. CC 1990, 1436.
17. (a) Paquette, L. A.; Sauer, D. R.; Cleary, D. G.; Kinsella, M. A.; Blackwell, C. M.; Anderson, L. G. JACS 1992, 114, 7375. (b) Cleary, D. G.; Paquette, L. A. SC 1987, 17, 497.
18. Trost, B. M.; Seoane, P.; Mignani, S.; Acemoglu, M. JACS 1989, 111, 7487.
19. Chaigne, F.; Gotteland, J. P.; Malacria, M. TL 1989, 30, 1803.
20. Trost, B. M.; Yang, B.; Miller, M. L. JACS 1989, 111, 6482.
21. Trost, B. M.; Balkovec, J. M.; Angle, S. R. TL 1986, 27, 1445.
22. Trost, B. M.; King, S. A.; Schmidt, T. JACS 1989, 111, 5902. Trost, B. M.; King, S. A. TL 1986, 27, 5971.
23. Trost, B. M.; King, S. A.; Nanninga, T. N. CL 1987, 15.
24. Trost, B. M.; Sharma, S.; Schmidt, T. JACS 1992, 114, 7903.
25. Jones, M. D.; Kemmitt, R. D. W. CC 1986, 1201.
26. Trost, B. M.; Schneider, S. AG 1989, 101, 215.
27. Trost, B. M.; Seoane, P. R. JACS 1987, 109, 615.
28. Trost, B. M.; MacPherson, D. T. JACS 1987, 109, 3483.
29. Bambal, R. B.; Kemmitt, R. D. W. JOM 1989, 362, C18.

Daniel A. Singleton

Texas A&M University, College Station, TX, USA



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.