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The substituted tetrahydrofuran core is a structural motif in many biologically active and natural compounds. However, the scarcity of enantioselective methods developed towards its synthesis makes this field challenging and attractive to explore. Herein, the first Brønsted‐base catalyzed enantioselective (3+2) annulation of donor‐acceptor cyclopropanes with aldehydes and ketones affording enantioenriched 2,3,5‐substituted tetrahydrofurans is reported. The reaction concept is based on activation of racemic β‐cyclopropyl ketones by a chiral bifunctional Brønsted base which catalyzes the (3+2) annulation for a range of aldehydes and ketones. For aldehydes, the annulation furnished tetrahydrofurans in excellent yield, good diastereoselectivity and with excellent enantioselectivity up to >99 % ee. Surprisingly, aromatic aldehydes afforded the cis‐2,5‐substituted tetrahydrofurans as the major diastereoisomer, while for aliphatic aldehydes the trans‐cycloadduct was favored. The reaction also proceeds well for ketones affording spiro tetrahydrofurans in excellent yields and enantioselectivities (up to 99 % ee). Hammett studies have been conducted to elucidate the influence of the electronic nature of benzaldehydes on the stereoselectivity. Based on the diastereochemical outcome for the aldehydes, two reaction paths for aromatic and aliphatic aldehydes are proposed. Finally, two diastereoselective synthetic transformations have been conducted to demonstrate the synthetic potential of the obtained products. [ABSTRACT FROM AUTHOR]

The reaction of styrene with butyrolactones in the presence of 2 equiv. each of AlCl3 and Mg and catalyzed by 10 mol.% of Cp2ZrCl2 in tetrahydrofuran led to the corresponding 1-phenyl-4-oxaspiro[2.4]heptanes in 47–57% yield. Presumably, the intermediates are zirconacyclopropane derivatives, similar to the Kulinkovich reagents. [ABSTRACT FROM AUTHOR]

Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1–3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1–3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process. Two types of coumarins-specific enzymes were identified which completed the last missing steps in linear/angular tetrahydropyrans or tetrahydrofurans coumarins biosynthesis. An acid/base-assisted epoxide ring opening contributed to pyran/furan ring refactoring. [Display omitted] [ABSTRACT FROM AUTHOR]

A Deep Eutectic Solvent, choline chloride/glycerol (1 : 2 mol mol−1), proved to be an effective and sustainable reaction medium to promote telescoped, one‐pot Mizoroki‐Heck cross‐coupling/reduction processes between 2,3‐dihydrofuran or 3,4‐dihydro‐2H‐pyran and several (hetero)aryl halides to easily access valuable 2‐(hetero)aryl tetrahydrofuran (THF) or tetrahydropyran derivatives in up to 95 % yield. Notably, the whole transformation takes place under aerobic conditions, in the absence of additional ligands, and with a good substrate scope. The practicability of the method is also exemplified by the sustainable synthesis of two key THF derivatives, which are side chains of pharmacologically relevant inhibitors of Kv1.2 channel. [ABSTRACT FROM AUTHOR]

A novel class of highly activated donor‐acceptor cyclopropanes bearing only a single, vinylogous acceptor is presented. These strained moieties readily undergo cycloadditions with aldehydes, ketones, thioketones, nitriles, naphth‐2‐ols and various other substrates to yield the corresponding carbo‐ and heterocycles. Diastereocontrol can be achieved through the choice of catalyst (Brønsted or Lewis acid). The formation of tetrahydrofurans was shown to be highly enantiospecific when chiral cyclopropanes are employed. A series of mechanistic and kinetic experiments was conducted to elucidate a plausible catalytic cycle and to rationalize the stereochemical outcome. [ABSTRACT FROM AUTHOR]

In this review, we have abstracted the various syntheses of acetogenins where the start point has been muricatacin. The latter can best be synthesized in either enantiomer form by the Sharpless method in three steps and can be admired as a gateway molecule for a quick assembly of many higher acetogenins. Muricatacin with orthogonally differentiated hydroxy groups and the available lactone carbonyl for chain elongation/modification can enable the concise synthesis of higher acetogenins. Many closely related synthetic intermediates possible from muricatacin are also abstracted here. The review should give impetus for future synthetic endeavours where the start point could be muricatacin and at least to the new molecules that are yet to be synthesized. [ABSTRACT FROM AUTHOR]

The regioselective ring opening of epoxy alcohols is an effective method for the synthesis of different types of oxacycles. The 5-exo opening being preferred vs. the 6-endo mode, according to Baldwin rules, the use of silyl-substituted oxiranes has been reported as a possible method to favor the 6-endo cyclization. However, there is a need for a detailed study on the different factors (structural factors, catalyst nature or conditions) that influence this process. In this paper, the acid-catalyzed cyclization of epoxysilyl alcohols was studied, focusing on the effect of substituents and reaction conditions on the outcome of the process. Two types of heterocycles (tetrahydrofurans or tetrahydropyrans) were selectively obtained depending on the structure of the initial epoxysilyl alcohol. Interestingly, cyclization of hindered epoxysilyl alcohols mainly proceeds through an unexpected side reaction, which implies a previous isomerization to an aldehyde. A mechanistic proposal for the formation of the different products is presented.

The highly diastereoselective synthesis of multiply substituted tetrahydrofurans was achieved in a sequential process under continuous flow conditions. Greatly reduced reaction times, improved selectivities and enhanced yields are the benefits of this approach in comparison to the initial batch synthesis. Moreover, gram amounts of product were produced in the flow reactor likewise due to facile upscaling. In addition, employing a novel bis(silyl)dienediolate tetrasubstituted tetrahydrofurans were made accessible as well. [ABSTRACT FROM AUTHOR]

The direct oxidative cyclization of 1,5-dienes is a valuable synthetic method for the (dia)stereoselective preparation of substituted tetrahydrofurans. Closely related reactions start from 5,6-dihydroxy or 5-hydroxyalkenes to generate similar products in a mechanistically analogous manner. After a brief overview on the history of this group of transformations and a survey on mechanistic and stereochemical aspects, this review article provides a summary on applications in natural product synthesis. Moreover, current limitations and future directions in this area of chemistry are discussed.

Abstract A method for the synthesis of 3,3-difluorotetrahydrofurans from iododifluoromethylated alcohols and 1,1-diarylethylenes is described. The reaction is performed under irradiation with 400 nm light emitting diodes in the presence of a cationic iridium(III) photocatalyst, [Ir(ppy) 2 (dtbbpy)]PF 6 , substoichiometric amounts of triphenylphosphine and sodium trifluoroacetate as a base. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Abstract: An efficient organocatalytic asymmetric synthesis of 2,3,4‐trisubstituted tetrahydrofurans and tetrahydropyrans has been developed using tandem iminium−enamine catalysis. The process comprises of a double Michael addition reaction between γ/δ‐hydroxy‐α,β‐unsaturated carbonyls and enals. The products of this reaction are obtained in high enantio‐ and diasteroselectivities and some further synthetic transformations have been performed. [ABSTRACT FROM AUTHOR]

Abstract: A series of highly substituted tetrahydrofurans (THFs), decorated with modifiable 2‐aryl, 3‐carboxy and 4‐amino substituents, has been prepared for biological evaluation within the European Lead Factory. Diastereoselective reductive amination of pre‐functionalised 4‐oxofurans, readily prepared from cinnamate esters via oxa‐Michael/Dieckmann annulation, provided the requisite THF cores on gram scale with three contiguous stereocentres, including full substitution at C‐3. In a second series, a pyrrolidine ring was fused to the same oxofuran scaffold via an intramolecular reductive amination, inverting the configuration at C‐4 relative to the other ring substituents. The resulting compounds, which displayed desirable physical properties as lead‐like scaffolds, were derivatised into a small library of 24 compounds, demonstrating their ability to serve as starting points for drug discovery. Ultimately, this chemistry enabled the preparation of 1948 THF‐containing compounds for inclusion in the Joint European Compound Library. [ABSTRACT FROM AUTHOR]

Abstract: Among all metathesis reactions known to date in organic chemistry, the metathesis of multiple bonds such as alkenes and alkynes has evolved into one of the most powerful methods to construct molecular complexity. In contrast, metathesis reactions involving single bonds are scarce and far less developed, particularly in the context of synthetically valuable ring‐closing reactions. Herein, we report an iron‐catalyzed ring‐closing metathesis of aliphatic ethers for the synthesis of substituted tetrahydropyrans and tetrahydrofurans, as well as morpholines and polycyclic ethers. This transformation is enabled by a simple iron catalyst and likely proceeds via cyclic oxonium intermediates. [ABSTRACT FROM AUTHOR]

4-Benzoyl-3,5-diaryltetrahydrofuran-2,2-dicarbonitriles were first synthesized from 2,2-dicyano-3-aryloxiranes and chalcones at toluene reflux; the 4,5- cis products proved to be predominantly formed and were isolated. Whereas shortened reaction times were observed by using microwave irradiation or catalytic cuprous chloride, no significant stereoselectivity change was in general noticed. Reacting 2,2-dicyano-3-aryloxiranes with 2-cyclopentenone next afforded 3-aryl-4-oxohexahydro-1 H -cyclopenta[ c ]furan-1,1-dicarbonitriles, and the endo stereoisomers were isolated. That no stereoselectivity change was noticed in the presence of cuprous chloride rather suggests an impact of the salt on the epoxide ring opening. Finally, treatment of 2,2-dicyano-3-aryloxiranes by 2-morpholinoacrylonitrile yielded 3-cyano-3-morpholino-5-phenyltetrahydrofuran-2,2-dicarbonitriles from which the preponderant trans isomers were isolated. Importantly, the molecular mechanism of the domino reaction between 2,2-dicyano-3-phenyloxirane and 2-cyclopentenone was studied. The rate-determining thermal ring opening of the oxirane is followed by a non-concerted pseudoradical -type reaction of the carbonyl ylide with 2-cyclopentenone. Using the bond evolution theory also allowed the regioselectivity of this non-polar reaction to be explained. [ABSTRACT FROM AUTHOR]

The enantioselective Rh-catalyzed Alder-ene cycloisomerization of ester- and ether-tethered alkyne allyl alcohols is an excellent entry to subsequent Rh-catalyzed one-pot hydrogenations in the sense of sequentially Rh-catalyzed processes to chiral alkylidene butyrolactone β-hydroxyethanes and alkylidene tetrahydrofuran β-aminoethanes, respectively, with excellent levels of enantioselectivity. [ABSTRACT FROM AUTHOR]

The development of a direct and highly stereoselective synthesis of 2,3,5-substituted tetrahydrofurans has been accomplished through a combination of batch- and microchip-MS-experiments. This sequential transformation comprises a Lewis acid-mediated reaction of bis(silyl) dienediolate 1 and a broad range of aldehydes, furnishing products with three new σ-bonds and three stereogenic centers in a one-pot process with typically good yields and excellent stereoselectivity. Key steps which have been elucidated primarily with microchip-MS-experiments include a vinylogous aldol reaction and a Prins-type cyclization. Furthermore, a titanium BINOL complex is a powerful chiral catalyst for this process. The products were further converted into bi- and tricylic products by carbonyl-ene reactions, proceeding with excellent yields and diastereoselectivity. [ABSTRACT FROM AUTHOR]

A novel visible-light-induced intramolecular chloroetherfication of electron-enriched styrenes is described. This approach provides a mild, alternative access to the synthesis of chlorinated tetrahydrofurans and tetrahydropyrans with high regio- and stereoselectivity. [ABSTRACT FROM AUTHOR]

A two-step stereoselective chemoenzymatic synthesis of optically active -aryl-substituted oxygen heterocycles was developed, exploiting a whole-cell mediated asymmetric reduction of α,β -, and γ-chloroalkyl arylketones followed by a stereospecific cyclization of the corresponding chlorohydrins into the target heterocycles. Among the various whole cells screened (baker's yeast, Kluyveromyces marxianus CBS 6556, Saccharomyces cerevisiae CBS 7336, Lactobacillus reuteri DSM 20016), baker's yeast was the one providing the best yields and the highest enantiomeric ratios (up to 95:5 er) in the bioreduction of the above ketones. The obtained optically active chlorohydrins could be almost quantitatively cyclized in a basic medium into the corresponding -aryl-substituted cyclic ethers without any erosion of their enantiomeric integrity. In this respect, valuable, chiral non-racemic functionalized oxygen containing heterocycles (e.g., (S)-styrene oxide, (S)-2-phenyloxetane, (S)-2-phenyltetrahydrofuran), amenable to be further elaborated on, can be smoothly and successfully generated from their prochiral precursors. [ABSTRACT FROM AUTHOR]

In this manuscript the kinetic resolution of 2-methoxycarbonylalk-3-enols is reported through a stereoselective selenocyclization promoted by an electrophilic sulfur-containing selenium reagent. Reacting one equivalent of the selenenenylating agent with two equivalents of racemic starting material afforded a mixture of a stereoselectively enriched tetrahydrofuran and the corresponding enantiomerically enriched alkenols. [ABSTRACT FROM AUTHOR]

Herein we present the synthesis of the anhydrophytosphingosine jaspine B and three of its stereoisomers using a carbohydrate-derived alkoxyallene in order to obtain the products in enantiopure form. Key step of the reaction sequence is the addition of the lithiated alkoxyallene to pentadecanal, setting the configuration at the later C-2 of the ring system. This reaction step proceeds with moderate selectivity and therefore leads to a stereodivergent approach to the natural product and its enantiomer. The gold-catalyzed 5-endo-cyclization affords the corresponding dihydrofurans, which after separation, azidation of the enol ether moiety and two subsequent reduction steps give the natural product and its stereoisomers.

The assembly of (Z)-chloro-exo-methylenetetrahydrofurans by an original and connective anionic cascade sequence is reported. Base-catalysed condensation of β-hydroxyketones with 1,1-dichloroethylene generates, in moderate to good yields, the corresponding (Z)-chloro-exo-methylenetetrahydrofurans. Acidic treatment of this motif leads to several unexpected dimers, possessing unique structural features.

Keywords: Deep eutectic solvents; Mizoroki-Heck reaction; Oxygen heterocycles; Tetrahydrofurans; Tetrahydropyrans EN Deep eutectic solvents Mizoroki-Heck reaction Oxygen heterocycles Tetrahydrofurans Tetrahydropyrans 1 1 1 01/20/23 20230117 NES 230117 B The Front Cover b illustrates the reaction conditions for the straightforward synthesis of oxygen heterocycles in Deep Eutectic Solvents. Front Cover: Ligand-Free Pd-Catalyzed Reductive Mizoroki-Heck Reaction Strategy for the One-Pot Synthesis of Functionalized Oxygen Heterocycles in Deep Eutectic Solvents (Eur. J. Org. Deep eutectic solvents, Mizoroki-Heck reaction, Oxygen heterocycles, Tetrahydrofurans, Tetrahydropyrans. [Extracted from the article]

The rearrangement under oxidative conditions of 3-(benzyloxy)-tetrahydro- 2,6,6-trimethyl-2H-pyran-2-carbaldehydes to afford a chiral protected tetrahydrofuran lactol is described.

An unprecedented enantioselective oxa-Michael reaction of α-tertiary alcohols using cinchona-alkaloid-based chiral bifunctional squaramide catalysts is reported. An oxidative dearomatization of phenol followed by an enantioselective oxa-Michael addition sequence provided a broad array of chiral sterically hindered tetrahydrofurans and tetrahydropyrans attached to a cyclohexadienone moiety in spiro fashion. In general, good yields and excellent enantioselectivities (up to 99 %) were observed. The chiral oxo-cycles obtained have easily been transformed into chromans without disturbing the enantioselectivity. [ABSTRACT FROM AUTHOR]

An oxidative bromoetherification involving a bromine transfer from alkyl bromides upon reacting them with aldehydes in a Grignard reaction with a concurrent oxidation of bromide was developed to provide substituted tetrahydrofurans in high yields. This reaction, which proceeds through two types of bromine transfer, was promoted by the addition of a Brønsted acid. Mechanistic studies suggested that a magnesium Lewis acid activates hypobromate, which is generated in situ from the reaction of bromide and Oxone to improve the electrophilicity of the bromonium ion (Br+) for the oxidative bromoetherification of alkenyl alcohols. Furthermore, the magnesium Lewis acid catalyzed oxidative bromoetherification of an alkenyl alcohol proceeded to provide a cyclization product in 92 % yield. [ABSTRACT FROM AUTHOR]

Titanocene(III) Chloride mediated radical induced synthesis of 4-benzylidene substituted tetrahydrofuran, a typical lignan skeleton, has been accomplished in good yield through addition-elimination route in racemic as well as in optically active forms. The method has been applied to the synthesis of furano lignans, magnofargesin ( 1) and 7-epimagnofargesin ( 2) in optically active forms. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

A new approach to the preparation of tetrahydrofurans and tetrahydropyrans through a photoredox catalytic process is described. The introduction of a phenylsulfanyl auxiliary group permits the substrates to be readily oxidized to form cationic intermediates for sequential intramolecular cyclization. The method features mild reaction conditions and operational simplicity. [ABSTRACT FROM AUTHOR]

L-Arabinose is an abundant resource available as a waste product of the sugar beet industry. Through use of a hydrazone-based strategy, L-arabinose was selectively dehydrated to form a chiral tetrahydrofuran on a multi-gram scale without the need for protecting groups. This approach was extended to other biomass-derived reducing sugars and the mechanism of the key cyclization investigated. This methodology was applied to the synthesis of a range of functionalized chiral tetrahydrofurans, as well as a formal synthesis of 3 R-3-hydroxymuscarine. [ABSTRACT FROM AUTHOR]

Intramolecular hydroalkoxylation of alkenols mediated by boron trifluoride etherate leads to substituted five-membered tetrahydrofurans and six-membered tetrahydropyrans in good yields. [ABSTRACT FROM AUTHOR]

Copper- or rhodium-catalyzed reactions of diazocarbonyl compounds with β-hydroxyketones give highly substituted tetrahydrofurans with excellent diastereoselectivity. Under mild conditions, the single-step process starts as a carbene OH insertion reaction, but is diverted by an intramolecular aldol reaction. [ABSTRACT FROM AUTHOR]

The Mitsunobu reaction between 4-diethoxyphosphoryl-2-hydroxymethyl-2-methyl-2,5-dihydrofurane and 6-chloropurine yielded 2-(6-chloropurin-9-ylmethyl)-4-diethoxyphosphoryl-2-methyl-2,5-dihydrofuran, which further reacted with sodium azide to afford 6-azidopurine derivatives. Reduction of the azido group resulted in the corresponding 6-aminopurine derivative, while under catalytic hydrogenation conditions both reduction of the azido group and hydrogenation of the dihydrofuran double bond occurred. [ABSTRACT FROM AUTHOR]

Lilac aldehydes are considered as principal olfactory molecules of lilac flowers. We have designed, prepared and evaluated two sets of their unnatural racemic analogues as pure diastereomers. While the synthesis of gem-dimethyl homologues starts from geranyl acetate, the preparation of methylene derivatives commences from linalyl acetate. The key Lewis and/or Brønsted acid catalysed cyclisation furnishes easily separable cis-/trans-tetrahydrofuranyl esters as common advanced intermediates. The subsequent functional group transformations lead to target aldehydes, alcohols, nitriles and olefins. Unlike the homologues possessing similar herbal scents, methylene derivatives exhibit woody and/or flowery odours. In the latter case, the sensory evaluation suggests the importance of relative stereochemistry and/or type of functional group on the odour character of respective compounds. [ABSTRACT FROM AUTHOR]

Abstract: Acid mediated, efficient Grob-type fragmentation reaction facilitated by vicinal ketal and ester moieties in variety of 5-oxabicyclo[2.1.1]hexanes leading to the corresponding annulated and 2,2,5-trisubstituted tetrahydrofurans is reported. Among the Brønsted and Lewis acids tested, BF3·OEt2 appears to give the best results, furnishing near quantitative yield (>99%) of tetrahydrofuran tricarboxylate derivatives under mild reaction condition. In case of unsymmetrical monosubstituted 5-oxabicyclo[2.1.1]hexanes two regioisomeric products are obtained. A strategy to transform one of the ester groups of the title compounds to protected hydroxymethyl moiety was evolved, which allows access to differentially protected 2-hydroxymethyl THF derivatives upon fragmentation. Employing TiCl4/R or S-BINOL as chiral Lewis acid, an enantioselective fragmentation (up to 66% ee) was described for the meso bis-furan derivative. [Copyright &y& Elsevier]

Abstract: The reaction of syn-1,2,4-triols under sulfonylation conditions catalyzed by Bu2SnO (5mol%) results in cyclization and the formation of 3-hydroxy tetrahydrofurans (56–85%) while the anti-1,2,4-triols react to give C1-O-sulfonyl derivatives in good yields (66–83%) and the cyclization product in poor yield (5–12%). A mechanism that justifies these observations is proposed to occur via the tosylation of the primary hydroxyl followed by an intramolecular tin acetal rearrangement to a 1,3-stannylene which then undergoes a 5-exo-tet-cyclization. The difference in rates of cyclization reactivity is due to the energetically more stable tin acetals of syn-1,3-diols compared to those of anti-1,3-diols. [Copyright &y& Elsevier]

Abstract: We described herein a Sn(NTf2)4-catalysed cyclisation of gem-(dialkoxymethyl)-1,6-dienes and derivatives where cyclohexane or tetrahydrofuran rings are formed following either a 6-enexo-endo-trig process or a 5-exo-trig process, respectively, depending on substitution patterns. The latter process features an unusual dealkylative ether cyclisation, triggered by the strong Lewis acid character of the tin(IV) triflimidate catalyst. [Copyright &y& Elsevier]

Abstract: Structurally diverse functionalized 4-(1-haloalkyl)-3-nitrotetrahydrofurans were conveniently obtained in moderate to good yield and moderate to very good diastereoselectivity by an oxidative tandem process consisting of conjugate addition reaction of lithium allyloxides to nitroalkenes followed by SET oxidation of the resulting nitronates. This triggers a radical cyclization; ligand transfer from the oxidant provides the products. The influence of the counter ion of the initial alkoxide and intermediate nitronate, the solvent and additives on the outcome of the tandem process was investigated. Optimal conditions for the tandem reactions consist of using butyllithium as the base for deprotonation in DME as the solvent. Cupric halides proved to be the SET oxidants of choice in the tandem reactions. A stereochemical model for the radical cyclization and ligand transfer steps is proposed. [Copyright &y& Elsevier]

A new diastereoselective synthetic approach towards 1,2,3-trisubstituted pyrrolidines and 2,3-disubstituted tetrahydrofurans is described. The synthesis of the pyrrolidines involves reductive cyclization of g-chloroketimines, which were generated in situ from the reaction of 3-substituted 5-chloro-2-pentanones and a primary amine. Various reduction conditions were explored to induce a diastereoselective reductive cyclization. 2,3-Disubstituted tetrahydrofurans were obtained by the direct reduction of 3-substituted 5-chloro-2-pentanones with sodium borohydride. [ABSTRACT FROM AUTHOR]