Annulation by sequential double Michael reaction; synthesis of decalones and its application to the syntheses of Îµ-cadinene, khusitone and khusilal

“…H NMR (400 MHz, CDCl 3 ): d = 1.10-1.30 (m, 10 H, 2 × CH 3 , H4aax, 1 × H5, 1 × H7, 1 × H8), 1.32-1.48 (m, 2 H, 1 × H5, 1 × H6), 1.48-1.56 (m, 1 H, 1 × H8), 1.58-1.70 (m, 3 H, H4eq, 1 × H6, 1 × H7), 1.77 (ddd, J 4ax,3eq = 5.5 Hz, J 4ax,4aax = 12 Hz, J 4,4 = 13.5 Hz, 1 H, H4ax), 1.98-2.12 (m, 2 H, 2 × H2), 2.53 (dd, J 1ax,2eq = 5 Hz, J 1ax,2ax = 12 HZ, 1 H, H1ax), 2.69 (dddd, J 3eq,2eq = ~2.5 Hz, J 3eq,4eq = ~2.5 Hz, J 3eq,2ax = ~5 Hz, J 3eq,4ax = ~5, × H5, 2 × H6, 2 × H7, 2 × H8), 1.93 (dddd, J 2eq,4 = 2 Hz, J 2eq,1ax = 4 Hz, J 2eq,3ax = 4 Hz, J 2,2 = 13 Hz, 1 H, H2eq), 2.09 (ddd, J 2ax,1ax = 13 Hz, J 2ax,3ax = 13 Hz, J 2,2 = 13 Hz, 1 H, H2ax), 2.26 (dd, J 1ax,2eq = 4 Hz, J 1ax,2ax = 13 Hz, 1 H, H1ax), 2.38 (dddd, J 3ax,2eq = 4 Hz, J 3ax,4eq = 4 Hz, J 3ax,2ax = 12 Hz, J 3ax,4ax = 12 Hz, 1 H, H3ax), 4.05-4.20 (m, 4 H, 2 × OCH 2 ), (OH not observed). J 2ax,1ax = 13 Hz, J 2ax,3ax = 13 Hz, J 2,2 = 13 Hz, 1 H,H2ax), 2.25 (ddd, J 4ax,4aeq = 5 Hz, J 4ax,3ax = 13 Hz, J 4,4 = 13 Hz, 1 H, H4ax), 2.51 (dddd, J 3ax,2eq = 4 Hz, J 3ax,4eq = 4 Hz, J 3ax,2ax = 13 Hz, J 3ax,4ax = 13 Hz, 1 H, H3ax), 2.88 (dd, J 1ax,2eq = 4 Hz, J 1ax,2ax = 13 Hz, 1 H, H1ax), 4.10 (q, J = 7 Hz, 2 H, OCH 2 ), 4.16 (q, J = 7 Hz, 2 H, OCH 2 ), (OH not observed) 13. C NMR (50 MHz, CDCl 3 ): d = 14.0 (2 × CH 3 ), 23.5 (C5 or C6 or C7), 25.8 (C5 or C6 or C7), 27.4 (C2), 28.0 (C5 or C6 or C7), 29.2 (C4), 36.9 (C3), 38.6 (C8), 41.4 (C4a), 42.5 (C1), 60.2, 60.6 (2 × OCH 2 ), 70.3 (C8a), 174.8 (C3-C=O), 175.6 (C1-C=O).…”

mentioning

confidence: 99%

Diversion from Bicyclo[4.2.0]octanol Formation Through the Use of Vinyl Electrophiles

Loughlin¹,

Rowen²,

Healy³

2005

Synthesis

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Bicyclo[4.2.0]octanols can be obtained from the reaction of phenyl vinyl sulfoxide and the lithium enolate of cyclohexanone under controlled conditions. Diversion to alkylation or MichaelMichael-ring closure was observed when alternative vinyl electrophiles were used. Novel bicyclic disulfones and hydroxyhexahydronaphthalenes were isolated. The use of a vinyl sulfoxide electrophile is crucial to the formation of bicyclo[4.2.0]octanols from simple ketones.Previously, the efficient assembly of bicyclo[n.2.0]alkan-1-ols was achieved by reaction of the lithium enolate of (simple) ketones and phenyl (or tolyl) vinyl sulfoxide (for example 1, Scheme 1). 1-4 Controlled reaction conditions are required to favour bicyclo[n.2.0]alkanol formation over alkylation products such as 2. 1 Notably alternate electrophiles have not been tested under the specific conditions required for bicyclo[n.2.0]alkanol formation. Now selected a,b-unsaturated electrophiles were considered in order to explore whether other novel functionality could be introduced to produce functionalized bicyclo[4.2.0]octan-1-ols in this process. Scheme 1Presently, the role of oxidation state and geometry at sulfur, and the polarity of the sulfur-oxygen bond in the electrophile were probed, using cyclohexanone as a representative ketone. Phenyl vinyl sulfide (3), phenyl vinyl sulfone (5), ethyl acrylate (6) and diphenylvinylphosphine oxide (7), were selected as electrophiles (Figure 1). Acrylonitrile was not considered due to its propensity to polymerise. Figure 1 a,b-Unsaturated electrophiles used in this workIn this study, the lithium enolate of cyclohexanone was generated from cyclohexanone or TMS cyclohexyl ether, either method giving similar results with phenyl vinyl sulfoxide (4) as previously described. 2 To allow for comparison, the lithium enolate of cyclohexanone was treated with electrophiles 3, 5-7 under conditions that had previously given moderate to good yields of bicyclo[4.2.0]octan-1-ols with 4 (-30°C, 5 min or -10°C, 10 min). 1

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“…3 The synthesis of khusitone 2 starting from 4-acetyldecaline-1,6-dione has been described, however synthesis of its tetrahydroderivative was not realized. 4 Herein a new synthetic method for the construction of the cyclohexane ring by tandem of free radical alkylation of the non-activated d-carbon atom 5 and a subsequent intramolecular carbanion cycloalkylation 6 was applied for the construction of the bicyclic skeleton of 14-norcadinane derivatives.…”

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confidence: 99%