ChemInform Abstract: PRACTICAL SYNTHESIS OF THE PROSTAGLANDIN SYNTHON 2‐(6‐(METHOXYCARBONYL)HEXYL)CYCLOPENT‐2‐EN‐1‐ONE

Abstract

Der 5‐Brompentylmalonsäurediester (III), erhalten aus dem Natriummalonat (I) und 1,5‐Dibrompentan (II), wird mit dem Kaliumsalz des Cyclopentanonesters (IV) zu dem Triester (V) kondensiert.

A One Pot Synthesis of Dehydrohedione (DHH) from a Hedione® Precursor

“…[19][20][21][22] Halogenation of ketones under these conditions is less regio-selective in MeCN, [29] as compared to the optimized co-solvent conditions AcOEt/CHCl 3 1:1. [23][24][25][26][27][28] For the use of t BuOH, see. [32] For analogous basic conditions (CuBr 2 , NaH, DMSO, or CuBr 2 , CaCO 3 , THF) on other substrates, see.…”

“…More recently, during a synthesis of Me‐jasmonate via the α ‐halogenation/dehydrohalogenation of 2‐(pent‐2‐yn‐1‐yl)cyclopentan‐1‐one, we encountered the additional problem of endo/exo ‐cyclic regioselectivity during the dehydrohalogenation, and could only minimize this drawback under neutral conditions . We thus similarly applied the Kochi 's methodology to 2a ,, and, to our delight, we obtained directly and cleanly, in a one pot, DHH 1a . This domino reaction, constitutes the shortest synthesis of 1a , thus avoiding trans ‐ Hedione ® 6a as a starting material for either halogenation/dehydrohalogenation,, or enol acetate formation/epoxidation/rearrangement, or HIO 3 oxidation,, , as key intermediate for the final hydrogenation towards the olfactively more appreciated cis ‐ Hedione ® 6b , or its even more powerful enantiomer (+)‐(1 R ,2 S )‐ cis ‐ 6b , named Paradisone ® ,…”

“…2 More recently, during a synthesis of Me-jasmonate via the a-halogenation/dehydrohalogenation of 2-(pent-2-yn-1-yl)cyclopentan-1-one, we encountered the additional problem of endo/exo-cyclic regioselectivity during the dehydrohalogenation, and could only minimize this drawback under neutral conditions. [17] We thus similarly applied the Kochi's methodology to 2a, [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33], 3 and, to our delight, we obtained directly and cleanly, in a one pot, DHH 1a. This domino reaction, constitutes the shortest synthesis of 1a, thus avoiding trans-Hedione â 6a as a starting material for either halogenation/dehydrohalogenation, [31][33] [34],4 1 For the diethyl 2-(3-oxo-2-pentylcyclopentyl)malonate analogue, see.…”

“…For a variant of the mechanism of formation, as suggested by Eschenmoser, see [2] ). Another very minor side product (< 5%), attributed to methyl 2-(3-methoxy-4-oxo-2-pentylcyclopent-2-en-1-yl)acetate on the basis of its MS analyses, was also present: 254 (6, M +Á ), 224 (90), 195 (12), 181 (30), 167 (50), 165 (25), 151 (66), 149 (24), 135 (22), 133 (22), 121 (19), 119 (13), 109 (33), 107 (50), 105 (22), 95 (26), 93 (22), 91 (24), 79 (31), 77 (24), 67 (17), 58 (25), 55 (25), 44 (57), 41 (28), 32 (45), 28 (100). For such related transformations, based on variations of Wallach's conditions, [36] using either Br 2 or FeCl 3 , see.…”

“… For the previous use of MeOH, see . Halogenation of ketones under these conditions is less regio‐selective in MeCN, as compared to the optimized co‐solvent conditions AcOEt/CHCl 3 1:1 . For the use of t BuOH, see .…”