Synthesis of Polycycles by Single or Double Domino Nucleophilic Substitution/Diels–Alder Reaction

Abstract

New hexacyclo and octacyclo compounds have been synthesized by a short route whose key step consists of a single or double domino nucleophilic substitution of neopentyl‐type iodides with potassium cyclopentadienide, followed by intramolecular Diels–Alder cycloaddition.

Generation and Reactions of an Octacyclic Hindered Pyramidalized Alkene

“…To solve this problem, we have prepared diiodide 38 according to Scheme 3. 5,5-Bisacetoxymethyl-1,3-cyclopentadiene 22 31 was reacted with ethyne-1,2-diylbis(phenyl)iodonium ditriflate 32, prepared as described, 23 and the crude product was directly reacted with an equimolar mixture of NaI and CuI to give the diiodide 34 in 35% yield.…”

“…1 H NMR (400 MHz, CDCl 3 ): δ = 0.96 [s, 9H, C(CH 3 ) 3 ], 1.37 (overlapped dd, 2 J (H,H) = 14,8 Hz, 3 J (H,H) = 2.8 Hz, 1H) and 1.39 (overlapped dd, 2 J (H,H) = 14.8 Hz, 3 J (H,H) = 2.8 Hz, 1H) (18-H a and 18-H b ), 1.41 (overlapped dd, 2 J (H,H) = 14.0 Hz, 3 J (H,H) = 2.8 Hz, 1H), and 1.43 (overlapped dd, 2 J (H,H) = 14.0 Hz, 3 J (H,H) = 2.8 Hz, 1H) (2-H a and 2-H b ), 1.50 (s, 1H, 10-H), 1.57 (d, 3 J (H,H) = 6.0 Hz, 1H, 11-H), 1.63 (d, 4 J (H,H) = 1.6 Hz, 1H, 19-H), 1.68 (s, 1H, 9-H), 1.77−1.81 (complex signal, 2H, 3-H and 17-H), 2.22−2.24 (broad s, 1H, 4-H), 2.27 (d, 3 J (H,H) = 6.0 Hz, 1H, 12-H), 2.30 (broad s, 1H, 13-H), 2.38 (broad s, 1H, 16-H), 2.41−2.43 (broad s, 1H, 7-H), 5.95 (dd, 3 J (H,H) = 5.6 Hz, 4 J (H,H) = 3.2 Hz, 1H, 5-H), 6.03 (overlapped dd, 3 J (H,H) = 5.6 Hz, 4 J (H,H) = 3.2 Hz, 1H, 15-H), 6.05 (overlapped dd, 3 J (H,H) = 5.6 Hz, 4 J (H,H) = 3.2 Hz, 1H, 14-H), 6.24 ppm (dd, 3 J (H,H) = 5.6 Hz, 4 J (H,H) = 3.2 Hz, 1H, 6-H). 13 Reaction of Diiodide 38 with Na/Hg in the Presence of 11,12-Dimethylene-9,10-dihydro-9,10-ethanoanthracene 14: Isolation of (3s,4R,7S,8R,9S,10s,11R,12S,13R,16S,17s,19s)-Octacyclo[10.6.1.0 1,10 .0 3,7 .0 4,9 .0 8,19 .0 11,16 .0 13,17 6,24 .0 1,28 .0 2,30 .0 3,18 .0 3,27 .0 4,16 .0 4,25 .0 5,13 .0 6,15 .0 8,12 .0 9,14 .0 16,23 .0 17,21 .0 20,27 .0 22,…”

Straightforward Synthesis of a Vicinal Double‐Bridgehead Iodo Trimethylsilyl Octacycle: Unprecedented Lack of Reactivity of the Silyl Group in the Presence of Fluoride Anions

“…The obtained yield corresponds to an average 87 % per synthetic stage. Although the intramolecular Diels–Alder reaction with the less substituted alkene moiety was to be expected, this was not the case for the more substituted, non‐electron‐deficient, and hindered alkene. Although octacycle 2 was fully characterized by spectroscopic means as well as by elemental analysis and accurate mass measurement, its structure was confirmed by X‐ray diffraction analysis (Figure ).…”

“…We planned the preparation of the vicinal double‐bridgehead iodo‐trimethylsilyl polycycle 2 from the recently described 1,1‐disubstituted cyclopentadiene 1 in a process not requiring any iododecarboxylation step or reaction of a carbanion with trimethylsilyl chloride, as well as the generation of the pyramidalized alkene 3 by a procedure similar to that used by Lukin and Eaton to generate cubene to study its reactivity (Scheme ).…”