Alkoxylation of Steroids with Cupric Bromide: Alcohol

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

“…7 For the previous use of MeOH, see. [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.…”

“…The one-pot transformation of 5a into the b-bromo derivative 5c (BocNHNH 2 , ClCH 2 CH 2 Cl, 85°C, NBS, Et 3 N, Amberlyst-15, [87] ) failed 20 The situation did not improve under stepwise conditions 21 , while the known 4-bromo cyclopent-2-enone 5e [91] [92] also failed to give the desired conjugate addition, as 5l was rather isolated (dimethyl malonate, MeONa, MeOH, 40% yield) 22 Further demethoxycarbonylation (H 2 O, NMP, 155°, 97% yield) afforded 5m, a precursor of cis-11a [108 -111] (MeOH, 10% Pd/C, H 2 , 98% yield, 90:10 mixture of stereoisomers), which exhibits a typical floral, jasmine, green, elegant, and natural scent (for complementary analyses, see Supporting information). The unreported a'-substituted cyclopentenones 5i, 5j were prepared from 5a either quantitatively by equimolar addition of NBS in MeCN, catalyzed by TMSOTf at 20°C, [112]23 or by oxidation with 2.0 molequiv.…”

“…[39] [40] Compound 6e was initially obtained in very poor yield by Naef and Decorzant after Pb(OAc) 4 oxidation of 6a, in analogy to. [86][5] ) 20 For the transformation of the corresponding ketomethylenolether 5d into DHH 1a, see. [ [89] For the corresponding b-chloro analogue 5b, 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.…”