Synthesis of a chiral steroid ring D precursor starting from carvone

A convenient preparation of 3-isopropyl-1-methylcyclopentylmethanol and 1-isopropyl-3-methylcyclopentylmethanol via Favorskii rearrangement

“…13,14 As summarized in Scheme 2, (S)-(+)-carvone was hydrogenated to give (5S)-carvomenthone 2 as a C-2 epimeric mixture. 15 The subsequent reaction with sulfuryl chloride furnished 2-chloro-2-methyl-(5S)-isopropylcyclohexanone 3 as a C-2 epimeric mixture (3a/3e 4:1 ratio, estimated by 1 H NMR), a result matching the already reported chlorination of (5R)-carvomenthone which led to ent-3a (halogen axial 77%) and ent-3e (halogen equatorial 23%).…”

“…13 C NMR spectra were recorded on a Varian Mercury Plus 400 spectrometer with CDCl 3 as a solvent. Chemical shifts (d) are given in parts per million (ppm) downfield from TMS as an internal standard.…”

A new route to keto and alkyl derivatives of (R)-carvone via diastereoselective conjugate addition of nitronate ions

“…The highly functionalised chiral cyclohexanones 10-12 can be view as excellent starting compounds for the total synthesis of enantiomerically pure natural products. [1][2][3][4][5][6] Experimental TBAF.3H 2 O solid, nitromethane (3), nitroethane (4), 1-nitropropane (5), 2-nitropropane (8), THF, benzene, AIBN, n-Bu 3 SnH and amberlyst-A21 were commercially available (Aldrich, Across or Merck) and were used as purchased. Methyl nitroacetate (6), 23 1,1-dimetoxi-3nitropropane (7) 24 were prepared according to literature procedures.…”

“…Both enantiomers of carvone are commercially available at low cost and have been extensively used as chiral starting material in enantioselective syntheses of natural products with diverse biological activities. [1][2][3][4][5][6] The functional richness of 1 allows different synthetic transformations such as conjugate additions, electrophilic additions to electron-rich double bond, frame rearrangement, α-alkylation, carbonyl 1,2addition, etc. In the case of conjugate addition, different nucleophiles have been added onto electron deficient double bond of 1, for example alkyl Grignard reagents, 7 organocopper reagents, 8 cyanide anion, 8 allyl organoindium reagent, 9 thiophenolate, 10 silyl enol ethers 11 and alcoholate.…”

Reaction of levoglucosenone with Dane’s diene

“…Unlike syntheses involving introduction of already finished D ring [11][12][13][14][15], including the chiral one [15][16][17][18][19][20][21], the use of levoglucosenone (1) as dienophile implies that, regardless of the cycloaddition result, the stereochemical structure of the adduct can be changed and subsequently modified toward estrone synthesis. Some intermediate products can be used to study structure-biological activity relationships.…”