Decarboxylative and dehydrative coupling of dienoic acids and pentadienyl alcohols to form 1,3,6,8-tetraenes

• Ghina’a I. Abu Deiab,
• Mohammed H. Al-Huniti,
• I. F. Dempsey Hyatt,
• Emma E. Nagy,
• Kristen E. Gettys,
• Sommayah S. Sayed,
• Christine M. Joliat,
• Paige E. Daniel,
• Rupa M. Vummalaneni,
• Andrew T. Morehead Jr,
• Andrew L. Sargent and
• Mitchell P. Croatt

Beilstein J. Org. Chem. 2017, 13, 384–392, doi:10.3762/bjoc.13.41

• 1,3,6,8-tetraenes. Contrary to related decarboxylative coupling reactions, an anion-stabilizing group is not required adjacent to the carboxyl group. Of mechanistic importance, it appears that both the diene of the acid and the diene of the alcohol are required for this reaction. To further understand

• this reaction, substitutions at every unique position of both coupling partners was examined and two potential mechanisms are presented. Keywords: decarboxylation; diene; dienoate; palladium; pentadienyl; tetraene; Introduction The construction of sp2–sp3 carbon–carbon bonds remains a difficult and

• ], nitro [26][27], or alkyne [21][28][29][30][31][32], Scheme 1), or use an aryl carboxylate [33][34] which typically requires the assistance of silver or copper(I) salts for the decarboxylative step. It is rare to use a pentadienyl electrophile [35], or to have a diene or simple alkene adjacent to the

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• . Rojas et al. proposed a convenient two-step pathway for the preparation of alkyl α,ω-dienes 3. These dienes are well-known precursors in ring-closing metathesis (RCM) and acyclic diene metathesis (ADMET) chemistry [32]. They first reported the quantitative α-alkylation of primary nitriles 1 [33]. In a

• second part of their work, they developed adequate conditions to carry out the decyanation reaction without olefin isomerization [18]. They explored several methods for the preparation of 12-butyltricosa-1,22-diene 3 (R = n-C4H9). The reaction was carried out in a slurry of K/Al2O3 in hexane, hexane

Diels–Alder reactions of myrcene using intensified continuous-flow reactors

• Christian H. Hornung,
• Miguel Á. Álvarez-Diéguez,
• Thomas M. Kohl and
• John Tsanaktsidis

Beilstein J. Org. Chem. 2017, 13, 120–126, doi:10.3762/bjoc.13.15

• fragrances are based on myrcene, such as geraniol, nerol, linalool, menthol, citral, citronellol or citronellal [3]. The terminal diene moiety present in myrcene allows for a reaction with a suitable dienophile following the Diels–Alder reaction mechanism. Dahill et al. describe the synthesis of the Diels

• . Results and Discussion The solution-phase Diels–Alder reactions presented herein follow the general reaction pathway shown in Scheme 1. The conjugated diene myrcene (1) was reacted with a series of dienophiles 2 to form the Diels–Alder adducts 3. Before investigating this reaction for continuous-flow

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• catalysts for aza-Diels–Alder reactions of Danishefsky’s diene with imines (Scheme 5) [52]. A variety of ammonium salts (L7–L10) including chiral cinchonidine derivatives L7 and catalyst L10 were found to promote the reaction in low-to-good yields albeit with no enantioselectivity. Although it is perhaps

• atoms covalently bonded to a benzylic carbon (Scheme 8). In 2016 Maruoka and Shirakawa followed up the aforementioned studies by demonstrating that tetraalkylammonium salts L5, L6, L11 and L12 as well as TBAI could activate imines toward aza-Diels–Alder reaction with Danishefsky’s diene (Scheme 9) [51

• coordinating TfO− anion did not accelerate the cycloaddition. In 2015, Takeda, Minakata and co-workers demonstrated that 2-iodoimidazolium salt L24 could serve as an efficient catalyst of the aza-Diels−Alder reaction of aldimines and Danishefsky diene (Scheme 19) [90]. Other organohalides such as

Identification, synthesis and mass spectrometry of a macrolide from the African reed frog Hyperolius cinnamomeoventris

• Markus Menke,
• Pardha Saradhi Peram,
• Iris Starnberger,
• Walter Hödl,
• Gregory F.M. Jongsma,
• David C. Blackburn,
• Mark-Oliver Rödel,
• Miguel Vences and
• Stefan Schulz

Beilstein J. Org. Chem. 2016, 12, 2731–2738, doi:10.3762/bjoc.12.269

• theoretically upper limit of 50%. We discovered that 6, sold by Acros Organics as racemic compound, was actually enriched in the desired (R)-enantiomer (see Supporting Information File 1 for optical rotation values). Diene (R)-9 was obtained by reduction of the epoxide 6 with LiAlH4 to form alcohol (R)-7

Synthesis of polyhydroxylated decalins via two consecutive one-pot reactions: 1,4-addition/aldol reaction followed by RCM/syn-dihydroxylation

• Michał Malik and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2016, 12, 2602–2608, doi:10.3762/bjoc.12.255

• 1,4-addition of vinylmagnesium bromide to sugar-derived cyclohexenone, followed by an aldol reaction with a derivative of but-3-enal. The obtained diene is then subjected to an assisted tandem catalytic sequence: ring-closing metathesis with the subsequent reuse of the Ru-catalyst in the syn

Diels–Alder reactions in confined spaces: the influence of catalyst structure and the nature of active sites for the retro-Diels–Alder reaction

• Ángel Cantín,
• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2016, 12, 2181–2188, doi:10.3762/bjoc.12.208

• Diels–Alder reaction selectivity [28]. The DAR of cyclopentadiene with p-benzoquinone is a well-known example of cycloadditions, and some results can be found on the control of the selectivity to the different isomers. In homogeneous phase, equimolar amounts of diene and dienophile afford two isomers

• second molecule of the diene to give again the kinetic endo-endo isomer. It is remarkable that neither the thermodynamic exo isomer nor the secondary exo-endo and exo-exo products were detected under our reaction conditions. Thus, the observed products, endo-endo and endo-exo are obtained in different

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• . Likewise, syntheses of fragments of natural products applying an oxidative cyclization protocol [1][2] and sequential epoxidation/cyclization procedures [3] are not in the scope of this article and are therefore not covered. Previous review articles concerning oxidative diene cyclization chemistry can be

• = Ac) or neryl acetate but seemed to be fairly general to other 1,5-diene substrates. Finally, they speculated on possible intermediates which may account for the outcome and the overall stereoselectivity of this unusual reaction. A mechanism, however, was not provided (vide infra). To date it is

• protocols using the three different d0-metals are highly diastereoselective (vide infra) and have been shown over the past decades to be applicable to a broad range of starting materials. Mechanistic aspects, stereochemistry and substrate scope of the direct oxidative diene cyclization Intrigued by the

Application of heterocyclic aldehydes as components in Ugi–Smiles couplings

• Katelynn M. Mason,
• Michael S. Meyers,
• Abbie M. Fox and
• Sarah B. Luesse

Beilstein J. Org. Chem. 2016, 12, 2032–2037, doi:10.3762/bjoc.12.191

• standard Ugi–Smiles adducts 3 (Table 3). The lack of oxatricyclic epoxyisoindoline formation is not surprising, given the more remote relative proximity of the diene and dienophile. Propargylamine and 3-butenylamine were also satisfying partners with 3-furaldehyde in this process. Ugi–Smiles reactions with

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• , Czech Republic Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA 10.3762/bjoc.12.184 Abstract The hetero-Diels–Alder reaction between a nitroso dienophile and a conjugated diene to give the 3,6-dihydro-2H-1,2-oxazine scaffold is useful for the synthesis of

• stereo- and regioselectivity for the synthesis of 1,2-oxazine scaffolds. Keywords: diene; hetero-Diels–Alder; nitroso compounds; regioselectivity; stereoselectivity; Review Introduction The hetero-Diels–Alder reaction represents one of the most important methods in organic synthesis, providing various

• biologically active compounds. It is a variant of the Diels–Alder reaction where either the diene or the dienophile contains a heteroatom. Hetero-Diels–Alder reactions between conjugated dienes and nitroso dienophiles affording 1,2-oxazines are utilized for the synthesis of many biologically active molecules

Mechanistic investigations on six bacterial terpene cyclases

• Patrick Rabe,
• Thomas Schmitz and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1839–1850, doi:10.3762/bjoc.12.173

• the substrate FPP is converted with a strict stereochemical course with respect to the fate of the diastereotopic methyl groups in FPP. These findings are in agreement with those reported for several other terpene cyclases [58][59][60], while the (1R,4R,5S)-guaia-6,10(14)-diene synthase from Fusarium

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• , Garner and co-workers have exploited a cycloaddition pathway between a poly-oxygenated diene and Garner’s aldehyde for constructing the carbohydrate core of amipurimycin [9]. Recently, Datta and co-workers reported the first synthesis of a fully-functionalized thymine analogue of amipurimycin, utilizing

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• ketone 265 was demonstrated by the transformation of this compound into (+)-sundiversifolide (266) (Scheme 81) [355]. The photooxidation of diene 267 followed by the base-catalyzed rearrangement of meso-endoperoxide 268 lead to (±)-trans,cis-4-hydroxy-5,6-di-O-isopropylidenecyclohex-2-en-1-one (269). The

A T-shape diphosphinoborane palladium(0) complex

• Patrick Steinhoff and
• Michael E. Tauchert

Beilstein J. Org. Chem. 2016, 12, 1573–1576, doi:10.3762/bjoc.12.152

• equiv of CpPd(η3-C3H5) in benzene. Complete conversion towards complex 9 with equimolar formation of 5-allylcyclopenta-1,3-diene was reached within 18 h at 50 °C. Complex 9 showed a singlet resonance at δ 41.0 in the 31P NMR spectrum and a broad resonance at δ 22 (w1/2 = 800 ± 50 Hz) in the 11B NMR

• those observed for its aryl derivatives (PhDPBPh ((o-PPh2-C6H4)2BPh) and PhDPBMes ((o-PPh2-C6H4)2B(Mes))). For these ligands the reaction with one equivalent of CpPd(η3-C3H5) leads to 50% consumption of CpPd(η3-C3H5) with simultaneous formation of 5-allylcyclopenta-1,3-diene, but complete conversion of

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• one epoxide hydrolase in the biosynthesis of the fungal polyketide aurovertin B (118) is sufficient to form this complex structural motif starting from a polyene-α-pyrone precursor (Scheme 18) [116]. The diene between C3 and C6 in 113 is first expoxidised by the FMO AurC. The epoxide hydrolase AurD

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• mechanism. Whereas the palladium-catalyzed Alder–ene reaction proceeds through an initial hydrometallation of a palladium hydride intermediate, ruthenium is speculated to first form a ruthenacyclopentene prior to β-hydride elimination. Since the hydrogen leading to the 1,3-diene is inaccessible to the

• ruthenacyclopentene, it must exclusively abstract the exocyclic hydrogen, which results in 1,4-diene formation. Palladium, which is not restricted to a metallacycle, is free to choose either hydrogen, and therefore performs β-hydride elimination on the allylic hydrogen. Recognizing that enantioenriched, cyclic

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• its derivatives is largely based on chemical theory and modeling with very little verified measurements. Therefore, the impact of isoprene on air quality and climate change remains highly uncertain. Isoprene or 2-methylbuta-1,3-diene is a volatile C5-organic compound generated by plants to help

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• reaction from a functionalized 1,3-diene like 2 (Figure 2) [13][14][15][16]. However, such a reaction would not be applicable to synthesize the bicyclo[3.2.1]octane core 3 of taxuspine C, as the mechanistic requirements in a Diels–Alder cycloaddition are not met with a 1,4-diene. Strategies that may access

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• desired azacycloalkenes 102a–c in 95–98% yield and 92–95 % ee (Table 11). Only the diene 100d did not cyclize and did not afford the nine-membered heterocycle by this methodology. In 2015, Hashimoto et al reported the synthesis of methyl 2-vinyltetrahydropyran-3-carboxylates (104) by an enantioselective

Indenopyrans – synthesis and photoluminescence properties

• Andreea Petronela Diac,
• Ana-Maria Ţepeş,
• Albert Soran,
• Ion Grosu,
• Anamaria Terec,
• Jean Roncali and
• Elena Bogdan

Beilstein J. Org. Chem. 2016, 12, 825–834, doi:10.3762/bjoc.12.81

• dienophile component in inverse-electron demand Diels–Alder reactions, a series of new dihydroindeno[1,2-c]pyran derivatives was synthesized. Thus, the addition of freshly distilled indene as a diene component to oxadiazinones 1 as the dienophiles [29] under acidic conditions (TFA, TFAA) led to the formation

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• electron-rich diene, which reacts with substituted dihydroisoquinoline 14 and dihydro-β-carboline 15, so that cyclohexanone derivatives 16 and 17 will be produced, respectively (Scheme 8) [19]. Also, a cyclic derivative of 13 was utilized (not shown). This aza-Diels–Alder reaction provides products with

• , the product was obtained in 78–90% yield and 15–92% ee. Finally, β-substituted α,β-unsaturated aldehydes were completely unreactive. In 2012, a proposed inverse electron-demand Diels–Alder reaction was reported by Wang and co-workers, obtaining enantiopure products 33, starting from diene 31 and

• of the nucleophile, making the diene more nucleophilic, and lowers the LUMO of the electrophile, making the dienophile more electrophilic (Scheme 19), thus the catalyst acts via a bifunctional mode. All these interactions are developed in the transition state through hydrogen-bonding, which controls

Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

• Stephanie R. Hare and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2016, 12, 377–390, doi:10.3762/bjoc.12.41

• (and simple diene isomers) [87], setting the stage for future studies aimed at elucidating the means by which abietadiene synthase steers its reaction away from rearrangement and at engineering abietadiene synthase so that it selectively forms rearranged products. Take home messages: • PTSBs can occur

Regioselective palladium-catalyzed ring-opening reactions of C1-substituted oxabicyclo[2,2,1]hepta-2,5-diene-2,3-dicarboxylates

• Michael Edmunds,
• Mohammed Abdul Raheem,
• Rebecca Boutin,
• Katrina Tait and
• William Tam

Beilstein J. Org. Chem. 2016, 12, 239–244, doi:10.3762/bjoc.12.25

Effective immobilisation of a metathesis catalyst bearing an ammonium-tagged NHC ligand on various solid supports

• Krzysztof Skowerski,
• Jacek Białecki,
• Stefan J. Czarnocki,
• Karolina Żukowska and
• Karol Grela

Beilstein J. Org. Chem. 2016, 12, 5–15, doi:10.3762/bjoc.12.2

• the surface of the support. To shed more light on this, we compared the behaviour of 8-powder and 8-C* in the RCM reaction of diene 9 conducted in ethyl acetate at 50 °C. Complex 8 is partially soluble in this solvent. The split tests, made during RCM reactions, revealed a great difference between the

New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand

• Agnieszka Hryniewicka,
• Szymon Suchodolski,
• Agnieszka Wojtkielewicz,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 2795–2804, doi:10.3762/bjoc.11.300

• potency of the new catalyst 9 was tested not only in standard, model metathesis reactions but was also examined in more demanding systems, such as conjugated dienes and polyenes (Table 4). The CM reaction between alkene and diene (or polyene) often suffers from low regio- and stereoselectivity control

• . The CM reaction may be accompanied by various self-metathesis processes. Additionally, due to the competitive cleavage of both double bonds of the diene substrate, two different products may be formed in the CM reaction between alkene and diene (Scheme 3). A further complication is a Z/E isomer

• . In all reactions the E-isomer of compound A was formed as a main product (Table 4, entries 1–3). Homodimerisation products of diene and alkene were obtained in very small amounts (<2% and <4% for entry 1 and 2, respectively, Table 4). The SM product of methyl vinyl ketone was not observed (entry 3