Efficient syntheses of 25,26-dihydrodictyostatin and 25,26-dihydro-6-epi-dictyostatin, two potent new microtubule-stabilizing agents

• María Jiménez,
• Wei Zhu,
• Andreas Vogt,
• Billy W. Day and
• Dennis P. Curran

Beilstein J. Org. Chem. 2011, 7, 1372–1378, doi:10.3762/bjoc.7.161

• mesylate 14 [36] gave alcohol 15 in 77% yield. Interestingly, the Marshall reaction works well even with mesylates containing a terminal alkyne; reaction of 13 with 16 provided 17 in 72% yield. The TIPS and primary TBS groups of 15 were simultaneously cleaved under basic conditions with TBAF [37] (88

• %), followed by protection of both primary and secondary hydroxy groups with TBSOTf to afford 18 in 96% yield. The terminal alkyne of 18 was then converted to the iodoalkyne with BuLi and I2 (92%), followed by diimide reduction with o-nitrobenzene sulfonylhydrazide (NBSH) [38] to the cis-vinyl iodide 19 in 94

Recent developments in gold-catalyzed cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2011, 7, 1075–1094, doi:10.3762/bjoc.7.124

• carboxyl unit on the metal-activated alkyne complex XXI. When a terminal alkyne is used (Figure 1, R = H), the 1,2-migration of the acetate moiety is preferred, affording an alkenyl–gold carbenoid species of type XXIII. In contrast, internal alkynes typically experience a 1,3-acyloxy migration rendering

Triazole–Au(I) complex as chemoselective catalyst in promoting propargyl ester rearrangements

• Dawei Wang,
• Yanwei Zhang,
• Rong Cai and
• Xiaodong Shi

Beilstein J. Org. Chem. 2011, 7, 1014–1020, doi:10.3762/bjoc.7.115

• -withdrawing groups were suitable for the reaction. Again, no indene by-products were observed in any of the tested cases, even with the electron-enriched p-OMe substituted alkyne 1d. These results highlighted the excellent chemoselective nature of the TA–Au catalyst. The terminal alkyne 1i did not give any

When gold can do what iodine cannot do: A critical comparison

• Sara Hummel and
• Stefan F. Kirsch

Beilstein J. Org. Chem. 2011, 7, 847–859, doi:10.3762/bjoc.7.97

• Kirsch and co-workers [114]. As shown in Scheme 18, these processes give the cyclization products in only poor yields. With regard to the scope, a terminal alkyne was required for the 6-exo cyclization mode to occur. As with all of the iodine mediated cyclizations discussed above, the cyclization mode is

Synthetic applications of gold-catalyzed ring expansions

• David Garayalde and
• Cristina Nevado

Beilstein J. Org. Chem. 2011, 7, 767–780, doi:10.3762/bjoc.7.87

• -trifluoromethylphenyl)phosphine gold(I) to give alkylidenecyclobutanone 12 quantitatively (Scheme 3, reaction 1) [19]. In an analogous manner, alkynylcyclobutanols were suitable substrates for gold(I)-catalyzed ring expansions only when a terminal alkyne group was present (Scheme 3, reaction 2). Thus, cyclobutanol 13

Gold-catalyzed heterocyclizations in alkynyl- and allenyl-β-lactams

• Benito Alcaide and
• Pedro Almendros

Beilstein J. Org. Chem. 2011, 7, 622–630, doi:10.3762/bjoc.7.73

• substituent at the terminal alkyne carbon showed a substantial effect on the reactivity, as illustrated by the fact that phenyl alkynol 31 gave a complex mixture of products. A conceivable mechanism for the formation of bicyclic tetrahydrofuran 27 from the methoxymethyl ether 28 may initially involve the

• -azetidinone nucleus [66][67]. Treatment of the terminal alkyne 35a with the catalytic system AuCl3/PTSA gave the desired ketal 36a. Appreciable amounts of a polar ketone arising from alkyne hydration were also produced. Fortunately, the [AuClPPh3]/AgOTf/PTSA system demonstrated better activity. Interestingly

Construction of cyclic enones via gold-catalyzed oxygen transfer reactions

• Leping Liu,
• Bo Xu and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2011, 7, 606–614, doi:10.3762/bjoc.7.71

• when a terminal alkyne, a TMS-substituted alkyne, or even an ester-substituted epoxide was used as the starting material. An 18O isotopic experiment helped the authors to propose an intramolecular oxygen transfer mechanism for the above transformation (Scheme 17). When employing the 18O incorporated

A gold-catalyzed alkyne-diol cycloisomerization for the synthesis of oxygenated 5,5-spiroketals

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2011, 7, 570–577, doi:10.3762/bjoc.7.66

• would quickly follow. Although this pathway seems unlikely to compete effectively with path a, a control experiment suggests that path b is feasible under certain conditions (Scheme 8, Reaction 4): We subjected terminal alkyne 21 to gold(I) chloride in methylene chloride and observed the formation of

One-pot gold-catalyzed synthesis of 3-silylethynyl indoles from unprotected o-alkynylanilines

• Jonathan P. Brand,
• Clara Chevalley and
• Jérôme Waser

Beilstein J. Org. Chem. 2011, 7, 565–569, doi:10.3762/bjoc.7.65

• A solution of 2-iodoaniline (4) (1 equiv), terminal alkyne (1.2–1.3 equiv), PdCl2(PPh3)2 (10 mol %) and CuI (10 mol %) was heated under reflux in Et3N (15 mL) for 1.5–2 h under a nitrogen atmosphere. The resulting mixture was filtered through Celite®, washed with DCM and concentrated under vacuum

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• ]. For this reaction 2-amino-5-methylpyridine (228) was condensed with an aldehyde to form an intermediate imine to which is added a terminal alkyne in the presence of copper(I) chloride. A copper(II) triflate catalyst is then used to promote a Lewis acid promoted 5-exo-dig heteroannulation to furnish

C–C (alkynylation) vs C–O (ether) bond formation under Pd/C–Cu catalysis: synthesis and pharmacological evaluation of 4-alkynylthieno[2,3-d]pyrimidines

• Dhilli Rao Gorja,
• K. Shiva Kumar,
• K. Mukkanti and
• Manojit Pal

Beilstein J. Org. Chem. 2011, 7, 338–345, doi:10.3762/bjoc.7.44

• on the surface of the charcoal. Once generated, the organo-Pd(II) species E then facilitates the stepwise formation of C–C bond via (i) trans organometallation with copper acetylide generated in situ from CuI and the terminal alkyne followed by (ii) reductive elimination of Pd(0) to afford 4

First synthesis of 2-(benzofuran-2-yl)-6,7-methylene dioxyquinoline-3-carboxylic acid derivatives

• Wentao Gao,
• Jia Liu,
• Yun Jiang and
• Yang Li

Beilstein J. Org. Chem. 2011, 7, 210–217, doi:10.3762/bjoc.7.28

• construction of the benzofuran moiety from intermediate 5. For the construction of 2-substituted benzofurans, the most widely used approach involves the palladium-catalyzed heteroannulation of 2-halophenols with a terminal alkyne via a tandem Sonogashira coupling-5-endo-dig-cyclization, largely based on the

Polar tagging in the synthesis of monodisperse oligo(p-phenyleneethynylene)s and an update on the synthesis of oligoPPEs

• Dhananjaya Sahoo,
• Susanne Thiele,
• Miriam Schulte,
• Navid Ramezanian and
• Adelheid Godt

Beilstein J. Org. Chem. 2010, 6, No. 57, doi:10.3762/bjoc.6.57

• reaction mixture to air. Opening the flask will immediately cause any unreacted terminal alkyne to undergo Glaser coupling. This is of no concern provided the alkyne dimer and the alkynyl–aryl coupling product can be easily separated, and this is what the HOM and related HOP group guarantee since they act

A thermally-induced, tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition approach to carbocyclic spirooxindoles

• Kay M. Brummond and
• Joshua M. Osbourn

Beilstein J. Org. Chem. 2010, 6, No. 33, doi:10.3762/bjoc.6.33

• spirooxindoles. However, when a terminal alkyne was subjected to the reaction conditions, only decomposition of the starting material was observed (entry 3, Table 1). When N-methylpyrrolidinone (NMP) was used as a solvent the reaction mixture could be heated to higher temperatures (250 °C vs. 225 °C in 1,2

Low temperature enantiotropic nematic phases from V-shaped, shape-persistent molecules

• Matthias Lehmann and
• Jens Seltmann

Beilstein J. Org. Chem. 2009, 5, No. 73, doi:10.3762/bjoc.5.73

• were evaluated using the datasqueeze software (http://www.datasqueezesoftware.com/). General method for preparation of intermediate products 3a–e The mixture of 1.0 equiv of thiadiazole 7, 1.0 equiv of the corresponding terminal alkyne 6a–e, 0.1 equiv of Pd(PPh3)4 and 0.05 equiv of CuI in piperidine is

Ring strain and total syntheses of modified macrocycles of the isoplagiochin type

• Andreas Speicher,
• Timo Backes,
• Kerstin Hesidens and
• Jürgen Kolz

Beilstein J. Org. Chem. 2009, 5, No. 71, doi:10.3762/bjoc.5.71

• [22]. The aldehyde 13 was transformed into the terminal alkyne 14 by chain extension [23] (Scheme 3). The coupling of the terminal alkyne 14 with the iodoarene 15 [24] as the “c” building block using a typical Sonogashira protocol [Pd(PPh3)4, CuI, Et3N] gave – even under an argon–hydrogen atmosphere

• , (*): configurationally semi-stable; o: configurationally unstable). Strategy of synthesis for the macrocycles 5–7. Preparation of the terminal alkyne 13 as a–b part (TBATB = tetrabutylammonium tribromide). Sonogashira-type coupling to the tolane 16. Synthesis of the d building blocks 21 and 26. aThe original procedure

Pd/C-mediated synthesis of α-pyrone fused with a five-membered nitrogen heteroaryl ring: A new route to pyrano[4,3-c]pyrazol-4(1H)-ones

• Dhilli Rao Gorja,
• Venkateswara Rao Batchu,
• Ashok Ettam and
• Manojit Pal

Beilstein J. Org. Chem. 2009, 5, No. 64, doi:10.3762/bjoc.5.64

• reaction of amine 4 to introduce the iodo group on the pyrazole ring followed by hydrolysis of the ester 5 yielded the desired acid 1. Our study started with the reaction of iodo acid 1 with a terminal alkyne, e.g. 1-hexyne (2a) and the results are summarized in Table 1. Due to our earlier success in the

• , all the terminal alkynes participated well in this coupling-cyclization reaction affording the desired products in moderate to good yields. Various substituents such as alkyl, hydroxyalkyl or aryl groups present in the terminal alkyne were well tolerated. The use of arylalkynes (Entries 7 and 8, Table

• reaction proceeds via a C–C bond forming reaction between the halide 1 and the terminal alkyne 2 in the presence of Pd(0) generated in situ. The resulting alkyne Z (Scheme 3) thus formed subsequently undergoes 6-endo-dig ring closure in an intramolecular fashion to give the desired product 3. A favorable

Pd/C- Mediated synthesis of indoles in water

• Mohosin Layek,
• Udaya Lakshmi,
• Dipak Kalita,
• Deepak K. Barange,
• Aminul Islam,
• K. Mukkanti and
• Manojit Pal

Beilstein J. Org. Chem. 2009, 5, No. 46, doi:10.3762/bjoc.5.46

• -iodoanilide 1 was treated with terminal alkyne 2 (3.0 equiv) in water in the presence of 10% Pd/C (0.03 equiv), PPh3 (0.12 equiv), CuI (0.06 equiv) and 2-aminoethanol (3.0 equiv) under nitrogen, 2-substituted indoles 3 were obtained in good yields (Scheme 1). The details of this study are summarized in Table

• entry 1, Table 1) confirming the requirement for an excess amount of terminal alkyne to achieve the best yield of the desired product. We have also examined the use of a basic iodoaniline such as N-methyl substituted 2-iodoaniline in the present coupling reaction with terminal alkynes. Isolation of 2

Regioselective alkynylation followed by Suzuki coupling of 2,4-dichloroquinoline: Synthesis of 2-alkynyl- 4-arylquinolines

• Ellanki A. Reddy,
• Aminul Islam,
• K. Mukkanti,
• Venkanna Bandameedi,
• Dipal R. Bhowmik and
• Manojit Pal

Beilstein J. Org. Chem. 2009, 5, No. 32, doi:10.3762/bjoc.5.32

• . (a) arylation at C-4 followed by alkynylation at C-2 or (b) alkynylation at C-2 followed by arylation at C-4. Methodologies based on strategy ‘a’ have been reported earlier. For example, Sonogashira coupling of a terminal alkyne with 2-chloro-4-aryl substituted quinoline [3] in the presence of (PPh3

The use of silicon- based tethers for the Pauson- Khand reaction

• Adrian P. Dobbs,
• Ian J. Miller and
• Saša Martinović

Beilstein J. Org. Chem. 2007, 3, No. 21, doi:10.1186/1860-5397-3-21

• low yields could be improved by optimizing the reaction conditions and finding a better way to add the second arm to the acetal, such as a catalytic method, avoiding the need for the bromosilane intermediate. This reaction was repeated using 3-butyn-1-ol to yield the isomeric, terminal alkyne product