Environmentally benign diastereoselective synthesis of granatane and tropane aldol derivatives

Synthesis of Dicarbonyl Curcumin Analogues Containing the Tropane Scaffold

“…Therefore we made the monosubstituted aldols via a known reaction of lithium enolates and subjected them to dehydration (elimination of water) in a separate step. Using LDA for making the enolate under typical conditions of aldol reaction gave monosubstituated exo,anti ‐aldols, which were isolated by crystallization typically in good yields (62–84 %, p ‐nitro derivative 27 %, Table ) and diastereoselectivities (single diastereomer by 1 H‐NMR). In the crude reaction mixture the minor isomer was barely detectable by NMR (doublet of lower coupling constant downfield of the exo , anti carbinol C H (OH) doublet).…”

“…The diastereomeric ratio is given in Table . For the sake of generality we opted for the lithium enolate based procedure over water promoted aldol reaction . The water promoted aldol reaction of tropinone, although experimentally simpler could not be used for poorly electrophilic aldehydes and often required longer reaction times.…”

“…The aldol products isolated by crystallization had exo , anti ‐configuration, which has been confirmed by comparison of 1 H‐NMR signals of C H (OH) with the literature. [23b], In the synthetic sequence these aldol reaction mixtures were used in the next step (i.e. elimination) without product isolation (crystallization of aldol significantly decrease the overall yields of 2‐benzylidenetropinones 4a–k ).…”

“…Mp 112–114 °C (lit. 111–113); 1 H NMR (400 MHz, CDCl 3 ): δ = 7.61 (br s, 1H), 7.22 (t, J = 8.0 Hz, 1H), 6.90–6.80 (m, 2H), 6.76 (dd, J = 8.0 Hz, 2.3 Hz, 1H), 5.18 (d, J = 3.1 Hz, 1H), 3.78 (s, 3H), 3.57 (d, J = 6.8 Hz, 1H), 3.50–3.42 (m, 1H), 2.83 (ddd, J = 14.2 Hz, 4.6 Hz, 2.9 Hz, 1H), 2.48–2.38 (m, 1H), 2.45 (s, 3H), 2.33–2.21 (m, 2H), 2.19–2.11 (m, 1H), 1.68–1.51 (m, 2H) ppm; 13 C NMR (100 MHz, CDCl 3 ): δ = 207.8, 159.4, 143.5, 129.0, 117.9, 112.7, 111.2, 76.4, 67.4, 64.2, 61.7, 55.0, 51.4, 40.5, 26.3, 26.2 ppm; FTIR (ATR): ν̃ = 2949, 2911, 1704, 1598, 1490, 1460, 1262, 1033, 878, 781, 702 cm –1 .…”

“…Mp: 102–104 °C (lit. 103–105); 1 H NMR (400 MHz, CDCl 3 ): δ = 7.89 (s, 1H), 7.25–7.15 (m, 2H), 6.99 (t, J = 17.4 Hz, 8.7 Hz, 2H), 5.20 (d, J = 2.5 Hz, 1H), 3.61 (d, J = Hz, 1H), 3.52–3.44 (m, 1H), 2.82 (ddd, J = 15.9, 4.5, 1.6 Hz, 1H), 2.46 (s, 3H), 2.41–2.46 (m, 1H), 2.35–2.11 (m, 3H), 2.70–2.60 (m, 1H), 2.58–2.50 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ): δ = 207.8, 161.9 (d, J C‐F = 244.7 Hz), 137.5 (d, J C‐F = 3.0 Hz), 127.0 (d, J C‐F = 8.1 Hz),114.8 (d, J C‐F = 21.4 Hz), 76.1, 67.4, 64.1, 61.6, 51.5, 40.5, 26.4, 26.2 ppm; 19 F NMR (376 MHz, CDCl 3 ): δ = –115.6 ppm (s, 1F); FTIR (ATR): ν̃ = 2945, 2875, 1707, 1603, 1506, 1460, 1410, 1215, 1073, 841, 767, 747 cm –1 .…”