1.
Triethylamine (99+%) was purchased from the Aldrich Chemical Company, Inc., and stored over sodium hydroxide.
2.
4-Dimethylaminopyridine (DMAP) (99%), 2-oxazolidinone (98%), methylmagnesium bromide (3 M in ether), and trimethylaluminum (2 M in toluene) were purchased from the Aldrich Chemical Company, Inc., and used as received.
3.
Methylene chloride (A.C.S. reagent) was distilled from calcium hydride prior to use.
4.
Trifluoromethanesulfonic anhydride was purchased from the Aldrich Chemical Company, Inc., and used as received. It can also be prepared from the acid according to the Organic Syntheses procedure.5
5.
Kieselgel 60 (230–400 mesh) was purchased from EM Science, an affiliate of E. Merck, Darmstadt.
6.
The product has the following properties: [α]D −6.6° (CHCl3, c 1.4); 1H NMR (CDCl3) δ: 4.81 (s, 2 H), 6.80 (bs, 2 H), 7.25 (6 H), 7.0 (4 H); 13C NMR (CDCl3) δ: 63.7, 127.0, 129.1 (2 C), 135.1.
7.
This procedure is essentially the same as that described in the literature.6
8.
This procedure involves three consecutive evacuations of the flask and fillings with dry argon.
9.
Reagent grade tetrahydrofuran, purchased from J. T. Baker Chemical Company, was freshly distilled from sodium metal and benzophenone.
10.
3-Bromopropionyl chloride (tech) was purchased from the Aldrich Chemical Company, Inc., and distilled prior to use.
11.
Anhydrous diethyl ether was freshly distilled from sodium metal and benzophenone.
12.
The product has the following properties: Rf = 3.1 (35% ethyl acetate in hexane, v/v); IR cm−1: 1785, 1675, 1419, 1396, 1321, 1258, 1220, 1024, 1008, 982, 752; 1H NMR (CDCl3) δ: 4.09 (t, 2 H, J = 8.0), 4.45 (t, 2 H, J = 8.0), 5.90 (dd, 1 H, J = 10.4, 1.6), 6.56 (dd, 1 H, J = 17.1, 1.6), 7.49 (dd, 1 H, J = 17.1, 10.4); 13C NMR (CDCl3) δ: 42.6, 62.1, 127.0, 131.6, 153.6, 165.0.
13.
1,2-Dichloroethane (99%, A.C.S. reagent) was freshly distilled from calcium hydride.
14.
Cyclopentadiene was prepared by thermal cracking of dicyclopentadiene available from the Aldrich Chemical Company, Inc., following the literature procedure.7
15.
Because of the high rate of the cycloaddition reaction it is very important that the cyclopentadiene solution enter the reaction flask and mix with the acrylate solution at as low a temperature as possible. For this reason it is beneficial to use a short cannula and to introduce the cyclopentadiene solution onto the wall of the flask that is deeply immersed in a solid CO2 bath.
16.
The product has the following properties: [α]D −152.0° (CHCl3, c 1.5; ee 89%), (lit.7 [α]D −65° (CHCl3, c 1.5; ee 38%); Rf = 0.23 (hexane-ethyl acetate 2:1, v/v); IR cm−1: 2975, 1775, 1696, 1386, 1337, 1279, 1253, 1226, 1111, 1039, 761, 704; 1H NMR (CDCl3) δ: 1.39–1.50 (m, 3 H), 1.95 (ddd, 1 H, J = 12.6, 9.3, 3.7), 2.93 (m, 1 H), 3.30 (m, 1 H), 3.91–4.00 (m, 3 H), 4.35–4.41 (m, 2 H), 5.87 (dd, 1 H, J = 5.5, 2.8), 6.24 (dd, 1 H, J = 5.5, 3.1); 13C NMR (CDCl3) δ: 29.5, 42.9 (2 C), 43.2, 46.4, 50.2, 61.9, 131.6, 138.1, 153.4, 174.7.
17.
The endo-exo selectivity of the cycloaddition reaction is higher than 50:1, since no signals corresponding to the exo product are observed in the 500 MHz 1H NMR spectrum of the crude or chromatographed product. The optical purity is 89% ee based on comparison with an authentic sample and the literature data.8 The optical purity is confirmed by a 500 MHz 1H NMR spectrum of the corresponding Mosher ester prepared in two steps: 1. Lithium aluminum hydride (LiAlH4) reduction in tetrahydrofuran at room temperature; 2. esterification of the resulting primary alcohol with (R)-(+)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride9 in the presence of triethylamine and DMAP in methylene chloride at room temperature.