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Synthesis 2002(12): 1695-1700
DOI: 10.1055/s-2002-33709
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 2,6-Dimethyltropone - A New, Convenient Methodology from
2,6-Dimethylcyclohexanone

Ambroz Almássya, Marek Pažickya, Andrej Bohác*a, Marta Salisováa, Gabriela Addováb, Myron Rosenblumc
a Department of Organic Chemistry, Comenius University, Faculty of Natural Sciences, Mlynská dolina, 842 15 Bratislava, Slovakia
Fax: +421(2)60296690; e-Mail: bohac@fns.uniba.sk;
b Chemical Institute, Comenius University, Faculty of Natural Sciences, Mlynská dolina, 842 15 Bratislava, Slovakia
c Department of Chemistry, Brandeis University, Waltham, MA 02254-9110, USA
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Publication History

Received 28 March 2002
Publication Date:
05 September 2002 (online)

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Abstract

Until now, 2,6-dialkyltropones have not been described. 2,6-Dimethyltropone (5) represents an appropriate material for synthesis of naturally occurring antiviral compounds. A new, convenient method for synthesis of 2,6-dimethyltropone (5) from 2,6-dimethylcyclohexanone in five optimized steps and 52% overall yield has been developed. Trimethylsilyl enol ether 1, prepared from 2,6-dimethylcyclohexan-1-one, was treated with dichlorocarbene, to give 7,7-dichloro-2,6-dimethyl-1-trimethylsilyloxybicy-­clo[4.1.0]heptanes (2). Acid promoted ring opening of 2 at room temperature gave 2-chloro-3,7-dimethylcyclohept-2-ene-1-one (3a). At higher temperatures (150-300 °C) a mixture of 3a and 2-chloro-3,7-dimethyl-1-trimethylsilyloxycyclohepta-1,3-diene (3b) was obtained in the ratio 2.1:1.0, respectively. Gamma bromination of 3a by NBS/AIBN gave diastereoisomers 4a and 4b in the ratio 5:1, which were converted to 2,6-dimethyltropone (5) by Li2CO3 in DMF at 120 °C. All new compounds were characterized by their NMR and HRMS spectra. The relative configuration and the structure of the preferred conformer of 3a and 4a were determined by HMQC, COSY and NOE NMR measurements.

Key words

tropone - cycloheptanes - conjugation - ketones - ring expansion - diastereoselectivity - shielding effect in NMR

1

Monoalkyltropones: 2-Me; [2a-k] [2u] 2-Et; [2a] [b] [2l-n] [2u] 2-n-Pr; [2b] [o] 2-i-Pr; [2b] [g] [m] [n] [2p-s] 2-n-Bu; [2b] [2r] [2t-v] 2-i-Bu; [2g] 2-t-Bu; [2w] 2-n-octyl; [2b] 3-Me; [2x] [y] 3-i-Pr; [2q-s] [2y] [3a] [b] 3-n-Bu [3c] [d] ; 4-Me; [2i] [j] [x] [3d-k] 4-i-Pr(Nezukon); [2h] [q] [r] [o] [3d] [3k-s] 4-n-Bu. [3l] Dialkyltropones: 2-Me-3-Me; [2l] [3t] [u] 2-Me-4-Me; [2j] [3v] 2-Me-5-Me; [2b] [j] [3t] [w] [x] 2-Me-7-Me; [2r] [3u] [y] [3a-e] 3-Me-5-Me; [4g] 3-Me-6-Me; [2y] 2-Et-7-Et; [4c] 2-i-Pr-5-Me; [2b] [3v] [x] 4-i-Pr-2-Me; [4f] 5-i-Pr-2-Me; [2l] [3v] 2-i-Pr-7-i-Pr; [2r] [4h] 4-n-Bu-2-Me; [4f] 4-n-Bu-2-Et; [4f] 2-t-Bu-7-t-Bu. [4e] Trialkyltropones: 2-Me-3-Me-5-Me; [2l] 2-Me-3-Me-7-Me; [4i] 2-Me-4-Me-7-Me; [2r] [4h] [j] [k] 2-i-Pr-7-i-Pr-4-Me; [2r] [4h] 2-t-Bu-7-t-Bu-4-Me; [4j] [m] 2-t-Bu-4-t-Bu-6-t-Bu. [4l] Tetraalkyltropones: 2-Me-4-Me-5-Me-7-Me; [2r] [4h] 2-i-Pr-7-i-Pr-4-Me-5-Me. [2r] [4h] Pentaalkyltropone: 2-Me-3-Me-4-Me-6-Me-7-Me. [4n-p]

15

The superscripts indicate toward which C-atom (a substituent or H-atom) is assigned hydrogen oriented [for example HCl-C(6) means the hydrogen at C(6) oriented toward to Cl].