Allylic Reagents Research Articles

ChemInform Abstract: Highly Diastereoselective Preparation of Aldol Products Using New Functionalized Allylic Aluminum Reagents.

AbstractThe title aluminum reagents are prepared from the corresponding allylic chlorides and aluminum powder as a solution in THF which is directly used in the reactions with the aromatic carbonyl compounds.

Reductive cross-coupling reactions between two electrophiles.

Reductive cross-electrophile coupling reactions have recently been developed to a versatile and sustainable synthetic tool for selective C-C bond formation. The employment of cheap and abundant electrophiles avoids the pre-formation and handling of organometallic reagents. In situ reductive coupling is effected in the presence of a transition-metal catalyst (Ni, Co, Pd, Fe) and a suitable metallic reductant (Mn, Zn, Mg). This Concept article assesses the current state of the art and summarizes recent protocols with various combinations of alkyl, alkenyl, allyl, and aryl reagents and highlights key mechanistic studies.

ChemInform Abstract: The Development of N‐Aryl Trifluoroacetimidate‐Based Benzyl and Allyl Protecting Group Reagents.

Abstractp‐Nitrophenyl substituted imidates (II) are efficient benzylating and allylating reagents in the presence of catalytic amounts of TmsOTf.

Highly Diastereoselective Preparation of Aldol Products Using New Functionalized Allylic Aluminum Reagents

Chloro-substituted triethylsilyl enol ethers derived from cyclohexanone and related ketones are converted with aluminum powder in the presence of indium trichloride to functionalized allylic aluminum reagents which represent a new type of synthetic equivalent of metal enolates. These allylic organometallics undergo highly diastereoselective additions to aldehydes and methyl aryl ketones, giving aldol products with a β-quaternary center.

Activation of Alkynes with B(C6F5)3 – Boron Allylation Reagents Derived from Propargyl Esters

Novel allyl boron compounds are readily synthesized via rearrangement reactions between Lewis acidic B(C6F5)3 and propargyl esters. These reactions proceed through an initial cyclization followed by ring-opening and concurrent C6F5-group migration. In the absence of disubstitution adjacent to the ester oxygen atom, an allyl boron migration rearrangement leads to formal 1,3-carboboration products. These allyl boron compounds act as allylation reagents with aldehydes introducing both a C3-allyl fragment and a C6F5-unit as a single anti-diastereomer. In these reactions, B(C6F5)3 activates the alkynes, prompting the rearrangement processes and enabling installations of C6F5 and R-groups.

Introduction of prenyl fragment into chalcones through α-regioselective 1,2-addition in THF

A practical and additive-free method for the prenylation of chalcones using prenylzinc is reported. The protocol described is attractive because it provides access to a new class of prenylated chalcone derivatives derived from two classes of natural products in a simple, high-yielding and regioselective synthetic step. Furthermore, the application of other allylic reagents in our new protocol is demonstrated. A plausible mechanism that invokes steric factors to account for the α-regioselective outcome is proposed.

Stereoselective Synthesis of Polyhydroxylated Amines Using (<i>S</i>)-Pyroglutamic Acid Derivatives

Naturally occurring polyhydroxylated amines such as (+)-1-deoxynojirimycin, polyoxamic acid, anisomycin, (-)swainsonine, and alexine stereoisomers, which have interesting biological activities including glucosidase- and mannosidase-inhibitory activity, immunoregulatory activity, and antibacterial effects, were synthesized stereoselectively starting from (S)-pyroglutamic acid derivatives. α,β-Unsaturated lactams ((S)-5-hydroxymethyl-2-oxo-3-pyrroline derivatives), α,β-unsaturated δ-lactone ((S)-4-amino-2-penten-5-olide derivative), and E-olefin ((S,E)-methyl-4-amino-5-hydroxypent-2-enoate derivative) from (S)-pyroglutamic acid derivatives were dihydroxylated using OsO4 in the presence of N-methyl morpholine N-oxide (NMO) to afford various chiral building blocks with different configurations. The stereoselectivity of cis-dihydroxylation for α,β-unsaturated lactams and α,β-unsaturated δ-lactone was very high, while the stereoselectivity was low for E-olefin. Therefore, the double asymmetric induction of E-olefin using K2OsO4 with chiral ligands was successively applied to yield high stereoselectivity. (2R,3S)-2-Hydroxymethyl-3-hydroxypyrrolidine and Gaissman-Weiss lactone, important intermediates for the preparation of pyrrolizidine alkaloids, were synthesized from a (3R,4R,5R)-3,4-dihydroxy-5-hydroxymethyl-2-pyrrolidinone derivative derived from α,β-unsatulated lactam. (+)-1-Deoxynojirimycin was synthesized from a (2S,3R,4R)-methyl 4-amino-2,3,5-trihydroxypentanoate derivative of E-olefin. (-)-Swainsonine and its stereoisomers were synthesized from (2R,3S,4R)- or (2R,3R,4R)-2-hydroxymethyl-3,4-dihydroxypyrrolidine derivatives of α,β-unsaturated δ-lactone or α,β-unsaturated lactam. The key reaction was diastereoselective allylation of the aldehyde derived from the corresponding 2-hydroxymethylpyrrolidine derivatives with various allylation reagents. The high diastereoselectivity could be explained by cyclic chelate formation between metals and the α-aminocarbonyl group or β-alkoxycarbonyl group, in which the nucleophile approaches from the less hindered face. Four alexine stereoisomers were synthesized from (2R,3R,4S,5R)- and (2R,3R,4S,5S)-2,3-dihydroxymethyl-3,4-dihydroxyl pyrrolidine derivatives of α,β-unsaturated lactam.

The retro Grignard addition reaction revisited: the reversible addition of benzyl reagents to ketones

The Grignard addition reaction is known to be a reversible process with allylic reagents, but so far the reversibility has not been demonstrated with other alkylmagnesium halides. By using crossover experiments it has been established that the benzyl addition reaction is also a reversible transformation. The retro benzyl reaction was shown by the addition of benzylmagnesium chloride to di-tert-butyl ketone followed by exchange of both the benzyl and the ketone moiety with another substrate. Similar experiments were performed with phenylmagnesium bromide and tert-butylmagnesium chloride, but in these two cases the Grignard addition reaction did not show any sign of a reverse transformation.

ChemInform Abstract: A Convenient Synthesis of α‐Substituted β,γ‐Unsaturated Ketones and Esters via the Direct Addition of Substituted Allylic Zinc Reagents Prepared by Direct Insertion.

ChemInform Abstract: A Convenient Synthesis of α‐Substituted β,γ‐Unsaturated Ketones and Esters via the Direct Addition of Substituted Allylic Zinc Reagents Prepared by Direct Insertion.

The development of N-aryl trifluoroacetimidate-based benzyl and allyl protecting group reagents

An exploration of the role of para-substituents on the balance between stability and reactivity of N-phenyl trifluoroacetimidates prompted the discovery of new reagents for the addition of allyl and benzyl protecting groups, namely O-allyl and O-benzyl N-(p-nitrophenyl)trifluoroimidates. These compounds are stable and crystalline at ambient temperature, making them ideal alternatives to existing benzylating and allylating reagents used under acidic conditions.

ChemInform Abstract: Structurally Defined Allyl Compounds of Main Group Metals: Coordination and Reactivity

AbstractReview: ca. 200 refs.

ChemInform Abstract: Air‐Stable Bifunctional Allylation Reagents for the Asymmetric Synthesis of Differentiated syn‐ and anti‐1,3‐Diols.

AbstractThe chiral bifunctional reagent (II) and its enantiomer are developed and successfully applied in the enantioselective synthesis of anti‐ (IV) and syn‐1,3‐diols, respectively, in high yields via aldehyde allylation followed by diastereoselective decarboxylative allylic etherification reaction.

ChemInform Abstract: Concise Asymmetric Synthesis of Orthogonally Protected syn‐ and anti‐1,3‐Aminoalcohols.

AbstractThe reaction of aldehydes (II) with novel chiral allylation reagent (I) leads to allyl carbonates (III), which are converted into orthogonally protected anti‐aminoalcohols (V) by an iridium‐catalyzed allylic amidation.

A Convenient Synthesis of α-Substituted β,γ-Unsaturated Ketones and Esters via the Direct Addition of Substituted Allylic Zinc Reagents Prepared by Direct Insertion

A practical and convenient procedure for the synthesis of α-substituted β,γ-unsaturated ketones and esters has been developed. Substituted allylic zinc reagents, prepared via direct metal insertion in substituted allylic halides, react readily with a broad range of acid chlorides and chloroformates furnishing the corresponding α-substituted β,γ-unsaturated ketones and esters in high yield and perfect regioselectivity.

Structurally Defined Allyl Compounds of Main Group Metals: Coordination and Reactivity

Organometallic allyl compounds are important as allylation reagents in organic synthesis, as polymerization catalysts, and as volatile metal precursors in material science. Whereas the allyl chemistry of synthetically relevant transition metals such as palladium and of the lanthanoids is well-established, that of main group metals has been lagging behind. Recent progress on allyl complexes of Groups 1, 2, and 12-16 now provides a more complete picture. This is based on a fundamental understanding of metal-allyl bonding interactions in solution and in the solid state. Furthermore, reactivity trends have been rationalized and new types of allyl-specific reactivity patterns have been uncovered. Key features include 1) the exploitation of the different types of metal-allyl bonding (highly ionic to predominantly covalent), 2) the use of synergistic effects in heterobimetallic compounds, and 3) the adjustment of Lewis acidity by variation of the charge of allyl compounds.

α-Selective Allylation of Azo Compounds Using Allylic Barium Reagents

The addition of allylic barium reagents to azo compounds was achieved with high α-regioselectivity. The double-bond geometry of allylic barium reagents was retained throughout the reaction at –78 °C and <i>E</i>- or <i>Z</i>-enriched allylic hydrazines were selectively obtained from the corresponding allylic barium reagents. An allylic hydrazine was efficiently converted into an allylic amine by reductive N–N bond cleavage.

Development and applications of remote stereocontrol using allylic organobismuth reagents

Reactions of 5-benzyloxy-4-methylpent-2-enyl(tributyl)stannane with aldehydes promoted by bismuth(III) iodide were usefully stereoselective in favour of the (E)-1,5-anti-6-benzyloxy-5-methylalk-3-en-1-ols. Similar stereoselectivity was observed for reactions of analogous 5-benzyloxy-4-methylpent-2-enyl bromides with aldehydes when promoted by a low valency bismuth species prepared by reduction of bismuth(III) triiodide with powdered zinc so providing a "tin-free" procedure. The analogous reactions of 4-benzyloxypent-2-enyl(tributyl)stannane with aldehydes promoted by bismuth(III) iodide were also stereoselective but gave lower yields. Attempted 1,6-stereocontrol using these reactions resulted in only modest stereoselectivities. Aspects of the chemistry of the products were studied in particular their stereoselective conversion into aliphatic compounds with methyl bearing stereogenic centres at 1,5,9,13- and 1,3,5-positions along the aliphatic chain. Mechanistically, allylic organobismuth species may be involved in both sets of reactions but this was not confirmed although the similar stereoselectivities observed for both the bismuth(III) iodide mediated reactions of the pent-2-enylstannanes and the low-valency bismuth promoted reactions of the pent-2-enyl bromides are consistent with participation of similar intermediates.

Cooperative Titanocene and Phosphine Catalysis: Accelerated C–X Activation for the Generation of Reactive Organometallics

The study presented herein describes a reductive transmetalation approach toward the generation of Grignard and organozinc reagents mediated by a titanocene catalyst. This method enables the metalation of functionalized substrates without loss of functional group compatibility. Allyl zinc reagents and allyl, vinyl, and alkyl Grignard reagents were generated in situ and used in the addition to carbonyl substrates to provide the corresponding carbinols in yields up to 99%. It was discovered that phosphine ligands effectively accelerate the reductive transmetalation event to enable the metalation of C-X bonds at temperatures as low as -40 °C. Performing the reactions in the presence of chiral diamines and amino alcohols led to the enantioselective allylation of aldehydes.

Facile and controllable synthesis of multiply substituted benzenes via a formal [3+3] cycloaddition approach

A facile direct [3+3] approach for the conversion of α,β-unsaturated carbonyls to multi-substituted benzenes using allylic phosphonium ylide reagents has been developed. The substituents and their positions on the benzene ring are controllable and predictable by the choice of an appropriate combination of α,β-unsaturated carbonyl compounds and ylides.

ChemInform Abstract: Approach to Highly Functionalized Oxazolones by a Pd‐Catalyzed Cyclization of N‐Alkynyl tert‐Butyloxycarbamates.

AbstractThe substrates are either treated under conditions A) to produce disubstituted pyrazolone structures or under conditions B) in the presence of allyl reagents to form trisubstituted derivatives.