1575-71-9Relevant articles and documents
Synthesis of a spirocyclic seco structure of the principal vetiver odorant Khusimone
Kraft, Philip,Denizot, Natacha
, p. 49 - 58 (2013)
The three-dimensional structure of tricyclic compounds with a zero-bridge to one bridgehead atom is determined by the underlying spirocyclic framework. (-)-Khusimone (1), the principal odorant of vetiver oil (content up to 2 %), is such a tricyclic norsesquiterpene, and dissection of the 7,8-bond between the methylene and the gem-dimethyl unit of 1 results in a spirocycle extending over an almost identical molecular volume and shape. Given that the vetiver rule postulates that one α-branched carbonyl osmophore in a certain spatial distance to a bulky moiety is responsible for the odor of vetiver, a 7,8-seco structure of 1 could prove or disprove these structural requirements. Therefore, (4R*,5R*)-7-isopropyl-4-vinylspiro[4.4]nonan-1-one [(4R*,5R*)-2] was synthesized in a 10-step synthetic sequence commencing with Steglich esterification of allyl alcohol (15) and isovaleric acid (14). Ireland-Claisen rearrangement of the formed allyl isovalerate (16) with subsequent lithium aluminum hydride reduction of resulting γ,δ-unsaturated acid 18, Appel bromination of corresponding alcohol 19, and ozonolysis provided 4-bromo-3-isopropylbutanal (23) in 19 % overall yield as a building block for the projected spiroannulation reactions. Although attempts on cyclopentanone (7) failed, cyclopent-2-en-1-one, via its TMS-trapped lithium 3-vinylcyclopent-1-enolate 12, turned out to be a successful starting material. Evans' variant of the Mukaiyama aldol reaction with 1-trimethylsiloxy-3-vinylcyclopent-1-ene (12) in the presence of BF 3·OEt2, followed by palladium-catalyzed conjugate tin hydride reduction of resulting enone 28 provided 2-(4′-bromo-3′- isopropylbutyl)-3-vinylcyclopentanone (29) in 50 % overall yield as the anlation precursor. LDA-mediated 5-exo-tet cyclization of 29 concluded the synthesis of the racemic 7,8-seco-/6-epi-7,8-secokhusimone mixture (4R*,5R*)-2, which possessed a floral, rosy, green, geranium-like odor with a threshold of 42.0 ng L-1 air, which is 10 times less intense than that of (-)-khusimone (1). Most importantly, seco structure (4R*,5R*)-2 did not display any woody nor any vetiver character, which proves the postulated vetiver rule wrong. Dissecting the bond between the methylene and the gem-dimethyl unit of khusimone leads to a spirocycle of almost identical shape, which was synthesized by 1,4-conjugate addition of a vinyl Gilman reagent, Mukaiyama aldol condensation of a bromo aldehyde prepared by Ireland-Claisen rearrangement of allyl isovalerate, and subsequent cyclization. Copyright
Synthesis method of apronal
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Paragraph 0054-0056; 0061-0066, (2019/12/11)
Belonging to the technical field of drug synthesis, the invention discloses a synthesis method of apronal. The method adopts commercial raw material isopropyl malonate diester as the starting raw material for reaction with allyl bromide or allyl chloride under an alkaline condition by one-pot process to generate dimethyl allyl isopropylmalonate, then hydrolysis is carried out to generate allyl isopropylmalonic acid, which is subjected to thermal decomposition to be further converted into acyl chloride for reaction with urea, thus obtaining apronal. The synthetic route adopted by the inventiononly needs two or three steps, the whole process is in simple in operation, the materials are easily available, the cost is low, and the yield is high, therefore the method is suitable for industrialproduction.
N -Boc amines to oxazolidinones via Pd(II)/bis-sulfoxide/br?nsted acid Co-catalyzed allylic C-H oxidation
Osberger, Thomas J.,White, M. Christina
supporting information, p. 11176 - 11181 (2014/08/18)
A Pd(II)/bis-sulfoxide/Br?nsted acid catalyzed allylic C-H oxidation reaction for the synthesis of oxazolidinones from simple N-Boc amines is reported. A range of oxazolidinones are furnished in good yields (avg 63%) and excellent diastereoselectivities (avg 15:1) to furnish products regioisomeric from those previously obtained using allylic C-H amination reactions. Mechanistic studies suggest the role of the phosphoric acid is to furnish a Pd(II)bis-sulfoxide phosphate catalyst that promotes allylic C-H cleavage and π-allylPd functionalization with a weak, aprotic oxygen nucleophile and to assist in catalyst regeneration.
