Bis(oxazolines) based on glycopyranosides – steric, configurational and conformational influences on stereoselectivity

• Tobias Minuth and
• Mike M. K. Boysen

Beilstein J. Org. Chem. 2010, 6, No. 23, doi:10.3762/bjoc.6.23

• (oxazoline) ligands [20][21]: Formation of bis(amide) 12 with dimethylmalonyl chloride, 3-O-acetylation and subsequent activation of the thioethyl moieties of 13 with NIS [30] for the double cyclisation step, led to benzylidene protected ligand 3-O-Ac alloBox 14 in excellent yield. As noted previously, the

• conformative effect is also in operation for allo-configured bis(oxazolines), we prepared ligand Ac alloBox 16 with acyclic 4,6-O-protection by the removal of the benzylidene groups from 12 under acidic conditions and per-O-acetylation in a one-pot reaction followed by NIS-mediated cyclisation of resulting bis

Fused bicyclic piperidines and dihydropyridines by dearomatising cyclisation of the enolates of nicotinyl-substituted esters and ketones

• Heloise Brice,
• Jonathan Clayden and
• Stuart D. Hamilton

Beilstein J. Org. Chem. 2010, 6, No. 22, doi:10.3762/bjoc.6.22

• : bicyclic; cyclisation; dearomatisation; enol ether; heterocycle; pyridine; quinoline; Introduction Oxidative [1][2][3] or reductive (nucleophilic) [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] dearomatising cyclisation reactions are effective strategies for rapidly building complexity

• carbocyclic ring by dearomatising cyclisation The study was initiated with the synthesis of the δ-nicotinyl ketone 7 as illustrated in Scheme 2. Ethyl benzoylacetate was alkylated with 3-(3-iodopropyl)pyridine 5 and the product 6 hydrolysed and decarboxylated to yield the pyridine 7 in moderate yield. On

• confirming the relative stereochemistry, and the assignment shown in Scheme 3 is on the basis that the benzoyl group of 8 is likely to lie on the exo face of the azadecalin system. We assume, in line with previous results [39], that cyclisation occurs only after the addition of the electrophilic trap (which

Benzyne arylation of oxathiane glycosyl donors

• Martin A. Fascione and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2010, 6, No. 19, doi:10.3762/bjoc.6.19

• synthesis of the key bicyclic intermediate was achieved starting from a simple thioglycoside 4 where the essential β-sulfur linkage was already installed, followed by a regio and stereoselective cyclisation onto the O-2 position to afford oxathiane glycosyl donor framework 5. The oxathiane ketal donor 5 is

Diastereoselective functionalisation of benzo-annulated bicyclic sultams: Application for the synthesis of cis-2,4-diarylpyrrolidines

• Susan Kelleher,
• Pierre-Yves Quesne and
• Paul Evans

Beilstein J. Org. Chem. 2009, 5, No. 69, doi:10.3762/bjoc.5.69

• Scheme 1, a Heck (Heck–Mizoroki) cyclisation [5][6][7][8][9] was employed to form the cyclic sulfonamide. Subsequently, it was shown that high stereofacial bias was achieved on hydrogenation, generating 2 as a single diastereoisomer. Treatment under dissolved metal reduction conditions afforded the cis

• and 6b which were used as substrates for the N–S and C–S bond cleavage forming arylsubstituted pyrrolidines [1][2][3]. In relation to this sequence attempts to achieve a reductive Heck cyclisation employing ammonium formate [12], gave only the product of bromine-hydrogen exchange 4c (where X = H

• ). Therefore, a one-pot method was developed based on recent reports which demonstrate that the residual palladium catalyst in Heck reactions may effectively mediate the addition of hydrogen to the newly substituted alkene [13][14][15]. Thus, following complete Heck cyclisation, as judged by TLC analysis, the

Three step synthesis of single diastereoisomers of the vicinal trifluoro motif

• Vincent A. Brunet,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2009, 5, No. 61, doi:10.3762/bjoc.5.61

• (Scheme 5). Instead the fluorinated tetrahydrofuran 14 was isolated as a crystalline product in 33% yield and its structure and stereochemistry were established by X-ray structure analysis (Scheme 5). This deviant reaction was surprising not only because there was no trace of the analogous cyclisation

• product after treatment of 8b with HF/pyridine, but also because cyclisation had occurred with retention of configuration at C4. One explanation for this outcome is that the reaction proceeds via a bicyclic phenoxonium intermediate 13 generated after HF promoted epoxide ring opening. Fluoride ion

• the requisite α,β-epoxy alcohols 6b and 7b. Three step sequential fluorination from α,β-epoxy alcohols to eg. the vicinyltrifluoro tosylate 11. Unexpected cyclisation of 9b to furan 14 with HF·pyridine. An X-ray structure of 14 (CCDC 750309) reveals that the cyclisation proceeds with a retention of

2-Phenyl- tetrahydropyrimidine- 4(1H)-ones – cyclic benzaldehyde aminals as precursors for functionalised β²-amino acids

• Markus Nahrwold,
• Arvydas Stončius,
• Anna Penner,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2009, 5, No. 43, doi:10.3762/bjoc.5.43

• acyclic resonance stabilised Schiff bases are preferentially formed. Consequently, one pot cyclisation protocols employing conditions such as KOH in protic solvents deliver the desired six-membered ring only in unsatisfactory yields [30][39]. An alternative approach to cyclise benzaldehyde-derived imines

• temperature. Despite the success in condensing 3 and benzaldehyde (dimethylacetal), all attempts to condense 3 with closely related acetophenone dimethylketal did not lead to any cyclisation product. To facilitate our selective ring opening concept, the N3-nitrogen of 4 had to be protected as a carbamate

• imidazolidinone rings [42]. Finally, enantiopure 2-phenyltetrahydropyrimidine-4(1H)-ones were successfully synthesised via a chiral pool approach by condensing Cbz-L-Asn-OAll (8) with benzaldehyde dimethylacetal (Scheme 4). Compared to the respective cyclisation reaction starting from 3, complete conversion of 8

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• -dimethoxyhydroquinone was then oxidized with silver(II) pinacolate (in poor yield) to give mitomycin K. 3.2. Naruta, Maruyama. Azide cycloaddition From a synthetic point of view, the intramolecular [1+4] cyclisation of a nitrene with a dienyl moiety gives a pyrrolizidine, the key structure found in mitomycins and many

• ]. With this substrate the subsequent cyclisation of azidodienylquinone 46 was performed with Cu(acac)2 as catalyst and afforded 48 with a high degree of diastereoselectivity. Thermal reaction led to the formation of the ring-contracted cyclopentendione derivative 54. The reaction was thought to proceed

• straightforward reactions then led to compound 80. As expected, the trans double bond in 80 prevented intramolecular alkylation of the amino group by the homoallylic bromide, thus explaining the somewhat surprising stability of this compound. The key step cyclisation was then carried out with the Nicolaou’s

Synthesis of new C^α-tetrasubstituted α-amino acids

• Andreas A. Grauer and
• Burkhard König

Beilstein J. Org. Chem. 2009, 5, No. 5, doi:10.3762/bjoc.5.5

• 327.2043. MF C17H29NO5. MW 327.42. Proposed reaction mechanism for the formation of Cα-tetrasubstituted tetrahydrofuran α-amino acids. Structure of compound 15 in the solid state determined by X-ray analysis [21]. Cyclisation reaction forming the tetrahydrofuran amino acid (TAA). Results of the reaction

Synthesis of chiral cyclohexanes and carbasugars by 6-exo-dig radical cyclisation reactions

• Rajeev K. Shrivastava,
• Elise Maudru,
• Gurdial Singh,
• Richard H. Wightman and
• Keith M. Morgan

Beilstein J. Org. Chem. 2008, 4, No. 43, doi:10.3762/bjoc.4.43

• gave mixtures of syn- and anti-alkynols 2a–2c which were separated following protection as methoxymethyl ethers. These were converted to the corresponding iodides which underwent 6-exo-dig radical cyclisation to afford chiral cyclohexanes and carbasugars. Oxidation of the primary alcohols 6a–b gave the

• corresponding aldehydes which on treatment with Grignard reagents afforded a mixture of alcohols. The corresponding iodides underwent similar 6-exo-dig cyclisation to give fully functionalised cyclohexanes. Keywords: carbasugars; cyclisation; cyclohexanes; 6-membered ring; stereoisomers; Introduction The use

• closure of a radical onto an alkyne [14]. In contrast there are fewer reports of the corresponding 6-exo-dig cyclisation to prepare fully functionalised cyclohexanes and carbasugars. The reason for this may be inferred from the observation that the formation of six-membered rings by a radical ring closure

Total synthesis of the indolizidine alkaloid tashiromine

• Stephen P. Marsden and
• Alison D. McElhinney

Beilstein J. Org. Chem. 2008, 4, No. 8, doi:10.1186/1860-5397-4-8

• centres on the stereoselective construction of the indolizidine core by capture of an electrophilic acyliminium species by a pendant allylsilane. The key cyclisation precursor is constructed using olefin cross-metathesis chemistry, which has the potential to facilitate both racemic and asymmetric

• approaches, depending upon the choice of the allylsilane metathesis partner. Results The use of the allyltrimethylsilane cross-metathesis approach enables the rapid construction of the key cyclisation precursor 3 (3 steps from commercial materials), which undergoes acid-induced cyclisation to give the

• -mediated reductive imide-olefin cyclisation [10]. Our own approach [14] utilises an intramolecular addition of an allylsilane to an N-acyliminium ion to deliver the [4.3.0]-azabicyclic (indolizidine) skeleton 2 (Scheme 1), wherein the pendant vinyl group acts as a handle to install the hydroxymethyl

Facile synthesis of two diastereomeric indolizidines corresponding to the postulated structure of alkaloid 5,9E- 259B from a Bufonid toad (Melanophryniscus)

• Angela Nelson,
• H. Martin Garraffo,
• Thomas F. Spande,
• John W. Daly and
• Paul J. Stevenson

Beilstein J. Org. Chem. 2008, 4, No. 6, doi:10.1186/1860-5397-4-6

• this intriguing transformation will be published elsewhere in due course. One-pot dehydration of the tertiary alcohol 3 was accomplished via the mesylate, and in situ elimination with triethylamine to give the diene 4 in 74% yield. Diene 4 smoothly underwent cyclisation to indolizidinone 5 when treated

Analogues of amphibian alkaloids: total synthesis of (5R,8S,8aS)-(−)-8-methyl- 5-pentyloctahydroindolizine (8-epi-indolizidine 209B) and [(1S,4R,9aS)-(−)-4-pentyloctahydro- 2H-quinolizin- 1-yl]methanol

• Joseph P. Michael,
• Claudia Accone,
• Charles B. de Koning and
• Christiaan W. van der Westhuyzen

Beilstein J. Org. Chem. 2008, 4, No. 5, doi:10.1186/1860-5397-4-5

• acylation of the chiral amine (−)-15, prepared as described in our prior work [13], with 5-bromopentanoyl chloride (obtained in two steps from δ-valerolactone) [27][28]. This afforded tert-butyl (3R)-[(5-bromopentanoyl)amino]octanoate (+)-25 in 98% yield (Scheme 3). However, subsequent cyclisation to the

• glacial acetic acid gave the free amine (−)-32 in quantitative yield. Treatment with 5-bromopentanoyl chloride as described above afforded the unstable bromoamide 33 as an orange oil in 89% yield. In this case, cyclisation of the crude intermediate to the lactam (+)-34 was most successfully effected by

• bromoacetate followed by treatment with triphenylphosphine and triethylamine in acetonitrile give the vinylogous urethane (+)-38 in 80% yield. Hydrolysis of the acetate with potassium carbonate in methanol then afforded the pivotal alcohol (+)-29 (70%). The scene was now set for cyclisation to the

Knorr- Rabe partial reduction of pyrroles: Application to the synthesis of indolizidine alkaloids

• Brendon S. Gourlay,
• John H. Ryan and
• Jason A. Smith

Beilstein J. Org. Chem. 2008, 4, No. 3, doi:10.1186/1860-5397-4-3

• (Scheme 3). The synthesis started with formation of the γ-pyrrolic ester 7 in high yield using an improved Clauson-Kaas synthesis [10], followed by boron tribromide mediated cyclisation to give the known bicyclic ketone 8 [11]. Upon subjection of this α-ketopyrrole 8 to the modified conditions reported by

Part 1. Reduction of S-alkyl- thionocarbonates and related compounds in the presence of trialkylboranes/air

• Jean Boivin and
• Van Tai Nguyen

Beilstein J. Org. Chem. 2007, 3, No. 45, doi:10.1186/1860-5397-3-45

• such as sugars.[3] On the other hand, iodides and S-alkylxanthates are useful compounds that easily produce carbon radicals involved in radical chain reactions (cyclisation, intermolecular addition onto an olefin, etc) in which trapping of the final radical results in the transfer of the iodine atom or

The tert- amino effect in heterocyclic chemistry: Synthesis of new fused pyrazolinoquinolizine and 1,4-oxazinopyrazoline derivatives

• Dipak Prajapati and
• Kalyan Jyoti Borah

Beilstein J. Org. Chem. 2007, 3, No. 43, doi:10.1186/1860-5397-3-43

• malononitrile and cyanoacetamide followed by cyclisation using anhydrous zinc chloride. Background The N-phenyl-3-substituted 5-pyrazolone derivatives are organic compounds that have been known since 1883; they are very useful as intermediates for pharmaceuticals and are used as anti-inflammatory agents and

• progress to understand the exact mechanism of the reaction. Conclusion In conclusion, we have demonstrated that N-phenyl-3-substituted pyrazolones can be used for the intramolecular alpha-cyclisation of tertiary amines [33] for the synthesis of pyrazolinoquinolizine and 1,4-oxazinopyrazoline derivatives in

The enantiospecific synthesis of (+)-monomorine I using a 5-endo- trig cyclisation strategy

• Malcolm B. Berry,
• Donald Craig,
• Philip S. Jones and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2007, 3, No. 39, doi:10.1186/1860-5397-3-39

• University, Private Bag 11 222, Palmerston North, New Zealand 10.1186/1860-5397-3-39 Abstract We have developed a general strategy for the synthesis of 2,5-syn disubstituted pyrrolidines that is based on the multi-faceted reactivity of the sulfone moiety and a 5-endo-trig cyclisation. This methodology was

• mode of cyclisation. [1][2][3][4][5][6] The methodology allows the conversion of epoxides (X = O) or aziridines (X = N-PG) (2) into the desired trisubstituted tetrahydrofurans or pyrrolidines (5) via a series of sulfone-mediated transformations (Scheme 1). Ring-opening 2 with the sulfone-stabilised

• anion of 1 forms the first C-C bond and furnishes 3. Modification of the work of Julia [7][8][9] then utilises the sulfone to facilitate stereocontrolled alkenylation to give the cyclisation substrate 4. Finally, 5-endo-trig cyclisation yields the desired heterocycles 5. Overall, the sulfone moiety

A convenient allylsilane- N-acyliminium route toward indolizidine and quinolizidine alkaloids

• Roland Remuson

Beilstein J. Org. Chem. 2007, 3, No. 32, doi:10.1186/1860-5397-3-32

• alkaloids ideal targets for total synthesis. We have developed a new method to generate bicyclic indolizidine and quinolizidine compounds based on an intramolecular cyclisation of acyliminium ions substituted by an allylsilyl side chain as an internal π-nucleophile (Scheme 1). [6] This reaction has proven

• and the important biological activities of the compound make this alkaloid an ideal target for total synthesis. [9][10][11][12][13][14][15][16] I 1.1 Intramolecular cyclisation We have found that intramolecular cyclisation of an allylsilane on an acyliminium ion constituted an excellent route to

• catalysed periodate oxidation of the olefinic bond of 6a and 6b led respectively to indolizidin-3-ones 7a and 7b. Upon treating an aqueous solution of 7a with 1N HCl the thermodynamically more stable indolizidinone 7b was obtained through a retro-Mannich fragmentation-cyclisation process. The last two steps

The first organocatalytic carbonyl- ene reaction: isomerisation- free C-C bond formations catalysed by H-bonding thio- ureas

• Matthew L. Clarke,
• Charlotte E. S. Jones and
• Marcia B. France

Beilstein J. Org. Chem. 2007, 3, No. 24, doi:10.1186/1860-5397-3-24

• reactions is severely limited. A step change in catalytic performance is required for this reaction to truly reach its potential. It remains to be seen whether the more entropically favoured intramolecular carbonyl ene cyclisation reaction holds more promise. In summary, we have developed the first

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

• . Saigo reported that the attempted P-K cyclisation of a variety of 3-sila-1,7-enynes underwent cycloisomerisation instead of the cycloaddition (Scheme 1).[7] Saigo's work showed that this cycloisomersiation was only applicable to 3-sila-1,7-enynes and any other chain length would undergo decomposition

• . Pagenkopf has shown that when the P-K cyclisation is carried out in 'wet' acetonitrile the cyclisation would proceed to give the cyclopentenones (Scheme 2).[8][9] The tethering strategy was not however successful in that although cyclisation gave the correct regiochemistry, the silicon tether is cleaved

• ] It can be seen that although the silicon methodology has been applied to the P-K reaction no group has been able to combine the synthetic diversity of silicon tethers with the synthetic benefits of the dicobalt octacarbonyl mediated cyclisation of alkynes and alkenes. Results and Discussion We

Novel base catalysed rearrangement of sultone oximes to 1,2-benzisoxazole- 3-methane sulfonate derivatives

• Veera Reddy Arava,
• Udaya Bhaskara Rao Siripalli,
• Vaishali Nadkarni and
• Rajendiran Chinnapillai

Beilstein J. Org. Chem. 2007, 3, No. 20, doi:10.1186/1860-5397-3-20

• )-one-2,2-dioxide Y = H), an obvious precursor for 5, was reported by Timoney et al., in an overall yield of ~30% [1] via the cyclisation of the methanesulfonate of salicylaldehyde followed by oxidation (Scheme 4). Results and discussion In order to prepare 6 in better yield, we choose methyl salicylate

• as the starting material and reacted it with methanesulfonyl chloride to provide the methanesulfonate derivative 9. After exploring different reaction conditions with NaOH and KOH as bases, it was found that NaH in DMSO was optimal for the cyclisation. Other strong bases also gave good yields of 6

Pd-catalysed [3 + 3] annelations in the stereoselective synthesis of indolizidines

• Olivier Y. Provoost,
• Andrew J. Hazelwood and
• Joseph P. A. Harrity

Beilstein J. Org. Chem. 2007, 3, No. 8, doi:10.1186/1860-5397-3-8

• the absence of the alkyllithium reagent. As outlined in Table 1, Entries 2–4, the annelation was found to proceed in the absence of n-BuLi, however, in all cases the yield of cyclisation product was significantly lower than with catalyst generated by the organolithium reagent. Whilst the underlying

• cyclisation onto the ester. Previous work in the quinolizidine area had shown that these transformations could be achieved in one-pot by the use of Mg turnings in methanol at ambient temperature [7][8]. Indeed, subjecting 10 to these conditions provided the desired indolizidine 11, albeit in modest yield

Tether- directed synthesis of highly substituted oxasilacycles via an intramolecular allylation employing allylsilanes

• Peter J. Jervis and
• Liam R. Cox

Beilstein J. Org. Chem. 2007, 3, No. 6, doi:10.1186/1860-5397-3-6

• interactions in the T.S. The 1,4-stereoinduction in these substrates is modest and seems to be modulated by the R substituent in the starting material. In the case of the syn-substrates, cyclisation through a chair T.S. is unlikely as this would require the methyl substituent α to the reacting carbonyl group

• stereoselective allylation of aldehydes (Scheme 2). [3] In this study, Lewis acid-mediated allylation of aldehyde 1, provided the oxasilacycle allylation products 2 and 3 in good yield. More significantly, owing to the complete 1,3-stereoinduction that is observed in this cyclisation, only these two – out of a

• large R groups in the cyclisation precursor 1, such as phenyl and cyclohexyl substituents, would serve as the most effective conformational anchors for our proposed chair-like T.S. (A values:[17] cyclohexyl: 2.2 kcal mol-1; phenyl: 2.8 kcal mol-1). These groups should occupy a pseudoequatorial position

One-pot synthesis of novel 1H-pyrimido[4,5-c][1,2]diazepines and pyrazolo[3,4-d]pyrimidines

• Dipak Prajapati,
• Partha P. Baruah,
• Baikuntha J. Gogoi and
• Jagir S. Sandhu

Beilstein J. Org. Chem. 2006, 2, No. 5, doi:10.1186/1860-5397-2-5

• cyclic imide system. Thus no C=O group (other than the cyclic imide system) was indicated either from IR or 13C NMR spectrum. The 1H NMR spectra showed the absence of C-5 proton of the uracil moiety which supported the involvement of a cyclisation process. The absence of NH/OH group could be explained

• synthetic scope this reaction, we reacted 1,3-dimethyl-6-hydrazinouracil 1 with an α-ketoalkyne (3-hexyn-2-one) in refluxing ethanol, the reaction proceeded somewhat differently from that with an enone (Scheme 2), as the intermediate could undergo a 5-exo-trig cyclisation in preference to 7-exo-trig. Here

• in any strong acid. Here the reaction proceeded initially by the Michael addition of α-ketoalkyne 8 to 1 followed by cyclisation to a 5-membered ring (Scheme 4). Conclusion In conclusion, our results demonstrate a simple, mild and efficient method for the synthesis of novel functionalised pyrimido

Stereoselective α-fluoroamide and α-fluoro- γ-lactone synthesis by an asymmetric zwitterionic aza-Claisen rearrangement

• Kenny Tenza,
• Julian S. Northen,
• David O'Hagan and
• Alexandra M. Z. Slawin

Beilstein J. Org. Chem. 2005, 1, No. 13, doi:10.1186/1860-5397-1-13

• preference (10:1) for the anti diastereoisomer 20 as confirmed by 1H-NMR nOe analysis (Scheme 5). Iodolactonisation of diastereoisomer 19 again generated a single product (3S, 5R)-20, indicating a much more stereoselective cyclisation. In order to improve the stereoselectivity of the aza-Claisen