Allylmetal Reagents Research Articles

Facile synthesis of homoallylamines via α-regioselectivity in ultrasonic mediation and γ-adduct syn-stereoselective allylation with AlCl3-catalysis

The allylation reaction of aldimines with allyl metal reagents is an important synthetic method for the preparation of homoallylamines. Therefore, we wish to report a highly regioselective and stereoselective allylation reaction under sonochemical Barbier-type reaction conditions. The high yields of regioselective α-adducts were achieved by reacting cinnamyl bromide, zinc, 1,2-dibromoethane, and aldimine in THF under sonochemical Barbier-type conditions. Highly regioselective and stereoselective allylation reactions were also achieved under Lewis acid-promoted Barbier-type reaction conditions.

Cobalt-Catalyzed Regiodivergent and Enantioselective Intermolecular Coupling of 1,1-Disubstituted Allenes and Aldehydes.

Catalytic enantioselective coupling of 1,1-disubstituted allenes and aldehydes through regiodivergent oxidative cyclization followed by stereoselective protonation or reductive elimination promoted by chiral phosphine-Co complexes is presented. Such processes represent unprecedented and unique reaction pathways for Co catalysis that enable catalytic enantioselective generation of metallacycles with divergent regioselectivity accurately controlled by chiral ligands, affording a wide range of allylic alcohols and homoallylic alcohols that are otherwise difficult to access without the need of pre-formation of stoichiometric amounts of alkenyl- and allyl-metal reagents in up to 92 % yield, >98 : 2 regioselectivity, >98 : 2 dr and >99.5 : 0.5 er.

Nickel-Catalyzed Reductive Allylation of Aldehydes with Allyl Acetates

AbstractCarbonyl allylation reactions constitute an important step in the formation of carbon–carbon reactions, and involve various related reactions that chiefly use allylmetal reagents. This report presents a nickel-catalyzed carbonyl allylation reaction using allyl acetate, which produces homoallyl alcohols in moderate to good yields, as an efficient methodology under reductive coupling conditions.

Copper-Catalyzed Asymmetric Reductive Allylation of Ketones with 1,3-Dienes.

A catalytic chemo-, regio-, and enantioselective allylation of ketones with 1,3 dienes in the presence of ( R, R)-Ph-BPE ligated Cu catalyst and hydrosilane is presented. This method provides a straightforward and alternative avenue to synthesize chiral homoallylic tertiary alcohols with 1,3-dienes as the latent allylic nucleophiles and avoids the traditional reliance on stoichiometric quantities of allylmetal reagents. This transformation proceeds under very mild conditions and displays good functional group tolerance and could be performed on a gram-scale.

Enantioselective Allylation Using Allene, a Petroleum Cracking Byproduct.

Allene (C3H4) gas is produced and separated on million-metric-ton scale per year during petroleum refining but is rarely employed in organic synthesis. Meanwhile, the addition of an allyl group (C3H5) to ketones is among the most common and prototypical reactions in synthetic chemistry. Herein, we report that the combination of allene gas with inexpensive and environmentally benign hydrosilanes, such as PMHS, can serve as a replacement for stoichiometric quantities of allylmetal reagents, which are required in most enantioselective ketone allylation reactions. This process is catalyzed by copper salts and commercially available ligands, operates without specialized equipment or pressurization, and tolerates a broad range of functional groups. Furthermore, the exceptional chemoselectivity of this catalyst system enables industrially relevant C3 hydrocarbon mixtures of allene with methylacetylene and propylene to be applied directly.

A convenient preparation of (S)-(−)-4-hydroxy-2-methylcyclopent-2-en-1-one and its application as a chiral synthetic equivalent of 2-methylcyclopent-2-en-1-one in the terpenoid synthesis

A method for the preparation of (S)-4-hydroxy-2-methylcyclopent-2-en-1-one from 1-(2-furyl)ethanol using modified Piancatelli rearrangement and enzymatic kinetic resolution of the racemate was developed. An application of O-protected derivatives of 4-hydroxy-2-methylcyclopent-2-en-1-one to terpenoid synthesis through tandem conjugate addition of allyl-metal reagents, enolate trapping, and consecutive Mukaiyama–Michael addition was studied. An optically active azulene derivative useful for terpenoid synthesis was efficiently synthesized.

Recent Development in Asymmetric Synthesis of Homo-allylic Amines Catalyzed by Small Organic Molecules

Chiral homo-allylic amines have been recognized in biologically active natural products and synthetic medicinal compounds. The most significant aspect of chiral homo-allylic amines relies on their synthetic versatility as chiral building blocks for the construction of a broad range of multi-functional organic compounds. A measure of the value of chiral homoallylic amines in organic synthesis is the large volume of work that has been devoted to their construction. Of the known asymmetric methods for their synthesis, the most popular method involves the formation of an imine followed by asymmetric allylation of the imine with reactive allylmetal reagents. An alternative approach is the metal-free asymmetric synthesis of chiral homo-allylic amines catalyzed by small organic molecules, which will be discussed in details in this review.

Reversible 1,4‐Insertion of Pyridine Into a Highly Polar Metal–Carbon Bond: Effect of the Second Metal

Dihydropyridines (DHPs) serve as selective reducing agents, are useful building blocks in organic chemistry, and represent an important class of pharmacologically active compounds. Transition-metal catalyzed 1,4-selective hydrosilylations and silaborations of pyridine have recently been reported as two new methods for the synthesis of DHPs. Remarkably, the hydrosilylation was found to be reversible. In general, the phenomenon of reversibility has been recognized for few insertion reactions of organotransition metal complexes. Some of these processes have been turned into applications such as dynamic polymerizations. In contrast, reversible insertion reactions are unusual for polar organometallic compounds of Group 1 and Group 2 metals. To the best of our knowledge, reversible insertion reactions into metal–carbon bonds have not been studied in detail for organometallic compounds of the heavy elements of Groups 1 and 2. We are interested in the reaction of pyridine with allyl metal reagents to give N-metalated DHPs in a one-step reaction. We report here the reversible 1,4-selective insertion of pyridine into a potassium– carbon bond and the synergetic stabilization of the insertion product by divalent metals. The instantaneous reaction of allylpotassium 1 with pyridine in THF at ambient temperature exclusively gave the 1,4-insertion product 2 (Scheme 1). Side products due to 1,2-insertion, deprotonative metalations, or pyridine coupling were not observed. Remarkably, exposure of 2 to 100fold excess of [D5]pyridine resulted in rapid exchange of the C5H5N core for a C5D5N core in an equilibrium reaction as observed by H NMR spectroscopy. [Li ACHTUNGTRENNUNG(C3H5)ACHTUNGTRENNUNG(PMDTA)] and [Na ACHTUNGTRENNUNG(C3H5)] showed similar reactivity patterns (for details see the Supporting Information). The pyridine exchange most likely proceeds via elimination of C5H5N from 2 to form back starting material 1, which then undergoes 1,4-insertion with deuterated pyridine. Rearomatization and entropy could be driving forces for the potassium assisted elimination reaction. Reactions of pyridine with main group organometallics are relatively well studied: insertion reactions with 1,2-selectivity (M=Li, Al), 1,4-selectivity (M=Mg, Ca), and mixtures thereof (M=Mg, Sn) have been reported. However, the reversibility observed in reactions of 2 is unprecedented for insertion reactions involving highly polar organometallic reagents. Compound 2 was isolated and characterized, but is not stable in THF or pyridine, irrespective of the presence of neutral chelating ligands. To investigate the exchange of the pyridine core of N-metalated DHPs in more detail, we sought for a way of stabilizing compound 2 while preserving its striking characteristic of reversibility. Recently, organometallic alkali zincates have been established as powerful tools in organic synthesis, as they can combine the high reactivity of their organoalkali component and the high selectivity of their organozinc component. When [K([18]c-6)] [Zn ACHTUNGTRENNUNG(h1-C3H5)3] (3 ; [18]c-6= [18]crown-6) was treated with excess pyridine, one equivalent of 1, and [18]c-6 (Scheme 2), dianionic tetrakis ACHTUNGTRENNUNG(amido)zincate 4 was obtained in quantitative yield. This is in contrast to reactions [a] Dipl.-Chem. C. Lichtenberg, Dr. T. P. Spaniol, Prof. Dr. J. Okuda Institut f r Anorganische Chemie RWTH Aachen University Landoltweg 1, 52056 Aachen (Germany) Fax: (+49)241-80-92644 E-mail : jun.okuda@ac.rwth-aachen.de [b] Dr. L. Perrin, Prof. Dr. L. Maron Universit de Toulouse et CNRS, INSA, UPS, CNRS UMR 5215 LPCNO 135 avenue de Rangueil, 31077 Toulouse (France) Fax: (+33)561-559-697 E-mail : Laurent.maron@irsamc.ups-tlse.fr Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201200808. Scheme 1. Reaction of allylpotassium 1 with pyridine to give the 1,4-insertion product 2. In the presence of excess [D5]pyridine, the C5H5N core in 2 is exchanged rapidly for a C5D5N core to give [D5]-2.

Diastereoselective additions of allylmetal reagents to free and protected syn-α,β-dihydroxyketones enable efficient synthetic routes to methyl trioxacarcinoside A.

Two routes to the 2,6-dideoxysugar methyl trioxacarcinoside A are described. Each was enabled by an apparent α-chelation-controlled addition of an allylmetal reagent to a ketone substrate containing a free α-hydroxyl group and a β-hydroxyl substituent, either free or protected as the corresponding di-tert-butylmethyl silyl ether. Both routes provide practical access to gram quantities of trioxacarcinose A in a form suitable for glycosidic coupling reactions.

Palladium Pincer Complex Catalyzed Funtionalization of Electrophiles

This review describes the usefulness of palladium pincer complexes in catalytic transformations of various electrophiles. We discuss two basic approaches to the functionalization of electrophiles: (i) palladium pincer complex catalyzed additions of allylic and other substrates to electrophiles, such as sulfonyl imines, aldehydes and related reagents; and (ii) pincer complex catalyzed generation of allylmetal reagents (such as boronates and other species) followed by a direct or palladium-catalyzed functionalization of the electrophiles under one-pot conditions. The study is focused on the reactivity and selectivity aspects of pincer complex catalysis. We show, for example, that allylations of imines and aldehydes are easier to perform with pincer complexes bearing π-acceptor phosphine ligands, while generation of organometallic species can be efficiently achieved by σ-donor, selenium or nitrogen containing pincer ligands. We present several examples of chiral pincer complexes in asymmetric catalysis. The high stability and well-defined stoichiometry of pincercomplexes allow a rational design of asymmetric catalytic reactions for carbon-carbon and carbon-heteroatom bond formations. Briefly, we have also reviewed the new emerging field of pincer complexes in Pd(II)/Pd(IV)-based catalytic cycles. These processes allow redox reactions involving pincer complex catalysts without altering of the typical pincer complex topology. Keywords: Palladium, catalysis, electrophiles, organoboronates, allylation, asymmetric catalysis, chiral metal complexes, pincer complexes, cyclopropanations, Michael additions, enantioselective transformations, Palladium Pincer Complexes, Allylic Stannanes, Allylic Cyanides, Benzylic Cyanides

Reactivity and Selectivity of Organotin Reagents in Allylation and Arylation: Nucleophilicity Parameter as a Guide

By using the inverse concept of electrophilicity and nucleophilicity and with two different available equations from the literature for electrodonating power, the global nucleophilicity index (N) of 99 organotin and 10 allylmetal reagents (metal = Mg, Zn, B, In, Si) have been calculated at the B3LYP/LAN2DZ, 6-31G(d) level of theory. The nucleophilicity scale is validated by the good linear fit between N-values of para-substituted arylstannanes and Hammett σp values of the substituents on the aryl ring. The global nucleophilicity index N has been utilized successfully to explain the reactivity of aryltin and allyltin reagents, to understand the effect of substituents directly attached to tin and those attached on the transferable group, and to rationalize the effect of solvents on reactivities of organotin reagents. The local nucleophilicity index value (Nk-) proved to be a useful local descriptor. The Nk- values at the α- and γ-position in various allylmetal reagents (metal = Mg, Sn, Zn, In, B, Si) have b...

ChemInform Abstract: Palladium‐Catalyzed Allylic C—OH Functionalization for Efficient Synthesis of Functionalized Allylsilanes.

A new method is described for palladium-catalyzed allylic silylation using allylic alcohols and disilanes as precursors. The reactions proceed smoothly under mild and neutral conditions, and this method is suitable for synthesis of regio- and stereodefined allylsilanes. The presented silylation reaction can be easily extended to include synthesis of allylboronates by change of the dimetallic reagent. The presented synthetic procedure offers a broad platform for the selective synthesis of functionalized allyl metal reagents, which are useful precursors in advanced organic chemistry and natural product synthesis.

Palladium-Catalyzed Allylic C−OH Functionalization for Efficient Synthesis of Functionalized Allylsilanes

A new method is described for palladium-catalyzed allylic silylation using allylic alcohols and disilanes as precursors. The reactions proceed smoothly under mild and neutral conditions, and this method is suitable for synthesis of regio- and stereodefined allylsilanes. The presented silylation reaction can be easily extended to include synthesis of allylboronates by change of the dimetallic reagent. The presented synthetic procedure offers a broad platform for the selective synthesis of functionalized allyl metal reagents, which are useful precursors in advanced organic chemistry and natural product synthesis.

ChemInform Abstract: Palladium‐Catalyzed Asymmetric Umpolung Allylation of Imines with Allylic Alcohols.

AbstractThe direct use of highly stable and easily available allylic alcohols instead of allylic metal reagents facilitates the preparation of chiral homoallylic amines.

Palladium-catalyzed asymmetric umpolung allylation of imines with allylic alcohols

A palladium-catalyzed asymmetric umpolung allylation reaction of imines with allylic alcohols has been developed. In the presence of chiral spiro phosphoramidite ligand 4, the allylation was accomplished with high yields and good enantioselectivities. The use of highly stable and easily available allylic alcohols instead of allylic metal reagents facilitated the preparation of chiral homoallylic amines.

Enantioselective allylation, crotylation, and reverse prenylation of substituted isatins: iridium-catalyzed C-C bond-forming transfer hydrogenation.

Enantioselective allylation, crotylation, and reverse prenylation of substituted isatins: iridium-catalyzed C-C bond-forming transfer hydrogenation.

Rationally Improved Chiral Brønsted Acid for Catalytic Enantioselective Allylboration of Aldehydes with an Expanded Reagent Scope

One of the most useful reactions in organic synthesis, the stereocontrolled addition of allylic metal reagents to carbonyl compounds, provides access to enantiomerically enriched homoallylic alcohols related to the acetate, propionate, and other oxygen-containing functionalities present in a large number of biologically active natural products and pharmaceutical drugs. In the search for an ideal carbonyl allylation methodology, the catalytic enantioselective allylboration presents numerous advantages such as a high chemo-, diastereo-, and enantiocontrol with stable and nontoxic pinacol allylic boronates. This article reports a rationally improved diol x SnCl(4) complex as chiral protic acid catalyst, which provides unprecedented levels of enantioselectivity in the catalytic allylation, methallylation, crotylation, and 2-bromoallylation of aliphatic aldehydes. The new diol, p-F-Vivol (4b), enables a more active diol x SnCl(4) catalyst that can compete more effectively with the background uncatalyzed allylboration. The usefulness of this optimized catalytic allylboration methodology was demonstrated with an efficient synthesis of the naturally occurring pyranone (+)-dodoneine and to the preparation of biologically important exomethylene-gamma-lactones.

Enantioselective Carbonyl Reverse Prenylation from the Alcohol or Aldehyde Oxidation Level Employing 1,1-Dimethylallene as the Prenyl Donor

Enantioselective transfer hydrogenation of 1,1-dimethylallene 1a in the presence of aromatic, alpha,beta-unsaturated, or aliphatic aldehydes 2a-i mediated by 2-propanol and employing a cyclometalated iridium C,O-benzoate derived from allyl acetate, m-nitrobenzoic acid, and (S)-SEGPHOS delivers reverse-prenylation products 4a-i in good to excellent isolated yields (65-96%) and enantioselectivities (87-93% ee). In the absence of 2-propanol, enantioselective carbonyl reverse prenylation is achieved directly from the alcohol oxidation level to furnish an equivalent set of adducts 4a-i in good to excellent isolated yields (68-94%) and enantioselectivities (86-91% ee). Competition and isotopic labeling experiments suggest rapid alcohol-aldehyde redox equilibration in advance of carbonyl addition along with capture of the kinetically formed pi-allyl complex at a higher rate than reversible beta-hydride elimination-hydrometalation. This protocol represents an alternative to the use of allylmetal reagents in enantioselective carbonyl reverse prenylation and represents the first use of allenes in enantioselective C-C bond-forming transfer hydrogenation.

ChemInform Abstract: Enantioselective Iridium‐Catalyzed Carbonyl Allylation from the Alcohol or Aldehyde Oxidation Level via Transfer Hydrogenation Coupling of Allyl Acetate: Departure from Chirally Modified Allyl Metal Reagents in Carbonyl Addition.

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Catalytic carbonyl addition through transfer hydrogenation: a departure from preformed organometallic reagents.

Classical protocols for carbonyl allylation, propargylation and vinylation typically rely upon the use of preformed allyl metal, allenyl metal and vinyl metal reagents, respectively, mandating stoichiometric generation of metallic byproducts. Through transfer hydrogenative C-C coupling, however, carbonyl addition may be achieved from the aldehyde or alcohol oxidation level in the absence of stoichiometric organometallic reagents or metallic reductants. Here, we review transfer hydrogenative methods for carbonyl addition, which encompass the first catalytic protocols enabling direct C-H functionalization of alcohols.