No abstract

1,1-Disubstituted vinyl triflates are synthesized by direct hydrotriflation of terminal alkynes employing a combination of TfOH and TMSN 3 in DCM at room temperature. Interestingly, under these conditions, only terminal alkynes were selectively converted to the corresponding vinyl triflates, while internal alkynes were not reacted. A broad range of substrates were successfully converted to the corresponding 1,1-disubstituted vinyl triflates in good to excellent yields even those with internal alkyne moieties present in the molecules.

We report a redox-neutral catalytic coupling of nitroalkanes and unactivated alkenes that proceeds by a directed carbopalladation mechanism. The reaction is uniquely enabled by the combination of PdI 2 as the precatalyst and HFIP solvent. Structurally complex nitroalkane products, including nitro-containing carbo-and heterocycles, are prepared under operationally convenient conditions without the need for toxic or corrosive reagents. Deuterium labeling experiments and isolation of a catalytically relevant intermediate shed light on the reaction mechanism. By taking advantage of different catalytic activation modes, we demonstrate orthogonal methods for site-selective functionalization of a polyfunctional nitroalkyl ketone. Density functional theory (DFT) calculations show that the carbopalladation transition state is stabilized by a Na•••I interaction and H•••I hydrogen bond with HFIP.

The generation of reactive carbocation intermediates from ortho-alkynylarylmethanol substrates was utilized as a means for the synthesis of aryl(1-indanyl)ketones . Substrates with a tertiary carbon at the β-position to the arene generated a carbocation intermediate via dehydration/protonation, followed by cyclization and hydration to give indanylketone products. For substrates with a quaternary carbon at that position, a carbocation intermediate was generated by protonation/elimination of water, followed by a 1,2-shift and a subsequent cyclization/hydration to give highly substituted indanylketones.

As equential synthesis of b-naphthols and naphtho [2,3-b]furan-2(3H)-ones (naphthofuranones) has been developed using ortho-alkynylarylketonesa st he substrates. The AgTFA-catalyzed ketonization generated the corresponding 1,5-diketonei ntermediates in situ;t hese weref urther cyclized via aldol condensation under basic conditions to obtain b-naphthol products in moderate to good yields. For the synthesis of naphtho[2,3-b]furan-2(3H)-ones, an additional lactonization step was appliedt og ive ab road range of products in good yields. Moreover,t his methodh as also been utilized in the synthesis of natural product negundin A.Scheme1.The reported methodsf or the synthesis of b-naphthols. Scheme2.Our methodology for the synthesis of5min KOH (10.0 equiv), MeOH, 85 8C, 3min < 59 [c] 585 8C, 5min LiOH (10.0equiv), MeOH, 85 8C, 1h < 58 [c] 685 8C, 5min KO t Bu (10.0 equiv), MeOH, rt, 1h < 34 [c] 785 8C, 5min KO t Bu (10.0 equiv), t-BuOH, rt, 1h < 42 [c] 885 8C, 5min KO t Bu (10.0 equiv), THF,rt, 1h -[d] 985 8C, 5min NaO t Bu (10.0 equiv), MeOH, rt, 1h < 51 [c] 10 H 2 O( 1.0 equiv), rt, 15 min KOH (10.0 equiv), MeOH,8 58C, 3min 61 11 H 2 O( 1.0 equiv), rt, 15 min KOH (10.0 equiv), MeOH,r t, 25 min 62 [a] Yields of isolated products are reported. [b] Only 1,5-diketone was observed.[ c] Product containedi mpurities. [d] Complex mixture. [e] O/N = overnight. Scheme3.Substrate scope.Y ields of isolated products are reported. [a] Only the 1,5-diketone was observed;[b] the reaction in step 1w as carried out at 85 8C. Scheme4.Substrate scope expansion. Yields of isolatedproducts are reported. [a] The reaction in step 1w as stirred at room temperature overnight; [b] the reaction in step 1 [b] was stirreda troomtemperaturef or 6h. Scheme5.Reactionmonitoring of compound 1z-OH. Scheme6.Scope of substrate for the synthesis of naphtho[2,3-b]furan-2(3H)ones. Yields of isolated products are reported.[a] The reaction in step 1was carried out at 85 8C. Scheme7.To tal synthesis of negundin A. 1 HNMR (400 MHz, CDCl 3 ): d = 7.66 (d, 1H, J = 8.4 Hz), 7.38-7.32 (m, 2H), 7.26-7.22 (m, 2H), 7.17-7.14 (m, 2H), 7.07-7.05 (m, 2H), 5.06

Eighteen hybrid compounds between 8-bromo-2-fluoro-isocryptolepine (4) and 1,2,3-triazole were synthesized via azide rearrangement-annulation reaction. Compound 4 underwent regioselective N-propargylation and click reaction to form 8bromo-2-fluoro-isocryptolepine-triazole hybrids 11 which were evaluated for cytotoxic activity. Compound 11 c containing 1anisyltriazole was the most effective in inhibiting HepG2, HuCCA-1 and A549 cell lines (IC 50 values of 1.65-3.07 μM) while compounds 11 a (1-phenyltriazole), 11 j (1-para-CF 3 -benzyltriazole) and 11 l (1-meta-Cl-benzyltriazole) were potent inhibitors of HuCCA-1, HepG2 and A549 cell lines, respectively. Moreover, 11 l showed the lowest cytotoxicity to normal human kidney cell line. Compounds 11 c and 11 l provided improvement of cytotoxic activity over 4. Compounds 4, 11 c and 11 l were selected to investigate their mechanisms of action. The results showed that 4 could induce G2/M cell cycle arrest and was involved in the upregulation of p53 and p21 proteins. However, the mechanisms of growth inhibition by 11 c and 11 l were associated with G0/G1 cell cycle arrest and mediated by induction of oxidative stress.

A cascade oxazole-benzannulation for the synthesis of naphtho [2,3-d]oxazoles has been developed employing orthoalkynylamidoarylketones as substrates. This procedure provides the advantage of preparing a wide variety of substituents on naphtho[2,3-d]oxazole structures. In addition, o-alkynylamidoarylketones could be prepared from easily accessible and a wide variety of commercially available starting materials. Therefore, this method is a judicious choice of strategy to synthesize naphtho [2,3d]oxazoles with a great variety of substituents. In this work, 27 examples were demonstrated to provide the desired products in moderate to good yields.

A facile approach to densely functionalized cyclopropanes is described. The reaction proceeds under mild conditions via the directed nucleopalladation of non-conjugated alkenes with readily available pronucleophiles and gives excellent yields and good anti-selectivity using I2 and TBHP as oxidants. Pronucleophiles bearing a diverse collection electron-withdrawing groups, including–CN, –CO2R, –COR, –SO2Ph, -CONHR and –NO2, are well tolerated. Internal alkenes, which are generally challenging substrates in other cyclopropanation methods, provide excellent yields and good diastereoselectivity in this methodology, allowing for controlled access to cyclopropanes substituted at all three C-atoms.