Rhodium‐Catalyzed Dynamic Kinetic Asymmetric Allylation of Phenols and 2‐Hydroxypyridines

Inspired by the mechanistic studies of rhodium‐catalyzed atom‐economic addition of carboxylate acids to allenes, a rhodium‐catalyzed dynamic kinetic asymmetric allylation of different nucleophiles with racemic allylic carbonates has been developed. High regio‐ and enantioselectivities can be obtained under neutral conditions and, furthermore, the chemoselectivities can be controlled by different diphosphine ligands. (R,R)‐QuinoxP* leads to selective O‐allylation of phenols, whereas when embedding (S,S)‐DIOP as the ligand, 2‐naphthol is ortho‐C‐allylated for the first time in high enantioselectivity. To this end, hydroxypyridines can be N‐allylated by Rh^I/(S)‐DTBM‐Segphos via the same intermediate as in the previously reported atom‐economic addition to allenes.     

Efficient Synthesis of N‐Alkylated 4‐Pyridones by Copper‐Catalyzed Intermolecular Asymmetric Propargylic Amination

Copper‐catalyzed intermolecular asymmetric propargylic amination with 4‐hydroxypyridines has been realized for the first time. In the presence of Cu complex derived from Pybox ligand, the N‐propargylated 4‐pyridones were obtained under mild reaction conditions with up to 99 % yield and 95 % ee. The Pybox ligand bearing a 4‐F‐phenyl substituent plays a key role for the high enantioselectivity. The products can be easily transformed to the core structure of quinolizidine alkaloids.     

Synthesis of 3‐Fluoropyrrolidines and 4‐Fluoropyrrolidin‐2‐ones from Allylic Fluorides

Various 3‐fluoropyrrolidines and 4‐fluoropyrrolidin‐2‐ones were prepared by 5‐exo‐trig iodocyclisation from allylic fluorides bearing a pending nitrogen nucleophile. These bench‐stable precursors were made accessible upon electrophilic fluorination of the corresponding allylsilanes. The presence of the allylic fluorine substituent induces syn‐stereocontrol upon iodocyclisation with diastereomeric ratios ranging from 10:1 to > 20:1 for all N‐tosyl‐3‐fluoropent‐4‐en‐1‐amines and amides. The sense and level of stereocontrol is strikingly similar to the corresponding iodocyclisation of structurally related allylic fluorides bearing pending oxygen nucleophiles. These results suggest that the syn selectivity observed upon ring closure involves I₂–π complexes with the fluorine positioned inside.     

Regio‐ and Stereoselective Allylic Substitutions of Chiral Secondary Alkylcopper Reagents: Total Synthesis of (+)‐Lasiol, (+)‐13‐Norfaranal,and (+)‐Faranal

Chiral secondary alkylcopper reagents were prepared from chiral secondary alkyl iodides by a retentive I/Li exchange followed by a retentive transmetalation with CuBr?P(OEt)₃. Switching the solvent to THF significantly increased their configurational stability and made these copper reagents suitable for regioselective allylic substitutions. The optically enriched copper species underwent S_N2 substitutions with allylic bromides (up to >99 % S_N2 regioselectivity). The addition of ZnCl₂ and the use of chiral allylic phosphates allowed to switch the regioselectivity towards S_N2′ substitution (up to >99 % S_N2′ regioselectivity) and to perform highly selective anti‐S_N2′ substitutions with absolute control over two adjacent stereocenters. This method was applied in the total synthesis of the three ant pheromones (+)‐lasiol, (+)‐13‐norfaranal, and (+)‐faranal (up to 98:2 dr, 99 % ee).     

Regio‐ and Enantioselective Synthesis of N‐Allylindoles by Iridium‐Catalyzed Allylic Amination/Transition‐Metal‐Catalyzed Cyclization Reactions

Regio‐ and enantioselective synthesis of N‐allylindoles was realized through an iridium‐catalyzed asymmetric allylic amination reaction with 2‐alkynylanilines and subsequent transition‐metal‐catalyzed cyclization reactions. The highly enantioenriched allylic amines prepared from Ir‐catalysis were treated with catalytic amount of NaAuCl₄ ? 2 H₂O or PdCl₂ providing various substituted N‐allylindoles in excellent yields and enantioselectivities.     

Alternative Synthesis of 2‐Hydroxy‐3,5,5‐trimethylcyclopent‐2‐en‐1‐one

The 2‐hydroxy‐3,5,5‐trimethylcyclopent‐2‐en‐1‐one ( 1 ) was synthesized in 42% yield by rearrangement of epoxy ketone 10 on treatment with BF₃⋅Et₂O under anhydrous conditions. Intermediate 10 was available from the known enone 8 , either via direct epoxidation (60% H₂O₂, NaOH, MeOH; yield 50%), or via reduction to the corresponding allylic alcohol 14 (LiAlH₄, THF), followed by epoxidation ([VO(acac)₂], ^tBuOOH) and reoxidation under Swern conditions, in 37% total yield.     

PEG‐4000‐promoted palladium‐catalyzed N‐allylation in water: aminonaphthalene as an example

An environmentally friendly, efficient catalytic process using palladium associated with ligands in a PEG4000–water system leading to N‐allylation was described in this study. PEG‐4000 was found to improve the palladium‐catalyzed allylic amination of allylic acetates with aminonaphthalenes and gave overall good to high yields of the corresponding N‐allylic aminonaphthalenes. Copyright © 2012 John Wiley & Sons, Ltd.     

Broadly Applicable Z‐ and Diastereoselective Ring‐Opening/Cross‐Metathesis Catalyzed by a Dithiolate Ru Complex

A broadly applicable Ru‐catalyzed protocol for Z‐selective ring‐opening/cross‐metathesis (ROCM) is disclosed. In addition to reactions relating to terminal alkenes of different sizes, the first examples of Z‐selective ROCM processes involving heteroaryl olefins, 1,3‐dienes, and O‐ and S‐substituted alkenes as well as allylic and homoallylic alcohols are reported. Z‐Selective transformations with an α‐substituted allylic alcohol are shown to afford congested Z alkenes with high diastereoselectivity. Transformations are performed in the presence of 2.0–5.0 mol % of a recently disclosed Ru‐based dithiolate complex that can be easily prepared in a single step from commercially available starting materials. Typically, transformations proceed at ambient temperature and are complete within eight hours; products are obtained in up to 97 % yield, >98:2 Z/E, and >98:2 diastereomeric ratio. The present investigations reveal a mechanistically significant attribute of the Ru‐based dithiolates that arises from electrostatic interactions with anionic S‐based ligands.     

Synthesis of (+) or (-)-2-(8′-Diphenylphosphino-1′-naphthyl)oxazoline Ligands and Their Application in Pd-Catalyzed Allylic Alkylation Reaction

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Synthesis of tetrahydrobenzo[b]furans via a gold(I)‐catalyzed rearrangement/cycloisomerization sequence of cyclic 1‐aryl‐2‐propargyl‐cyclohex‐2enols

A facile synthesis of tetrahydrobenzo[b]furans via gold(I)‐catalyzed cycloisomerization of 1‐aryl‐2‐propargylcyclohex‐2‐enols is described. The transformation is suggested to proceed through a gold(I)‐catalyzed tertiary allylic alcohol rearrangement to give a secondary allylic alcohol that underwent a 5‐exo‐dig addition of the hydroxyl group onto the gold(I)‐activated alkyne to give a vinylgold species. Protodeauration of the resulting vinylgold intermediate followed by aromatization furnished the tetrahydrobenzo[b]furans.     

Iridium‐Catalyzed Regio‐ and Enantioselective Allylic Substitution of Silyl Dienolates Derived from Dioxinones

Reported herein is the iridium‐catalyzed regio‐ and enantioselective allylic substitution reactions of unstabilized silyl dienolates derived from dioxinones. Asymmetric allylic substitution of a variety of allylic trichloroethyl carbonates with these silyl dienolates gave γ‐allylated products selectively in 60–84 % yield and 90–98 % ee.     

Iridium‐Catalyzed Enantioselective Allylic Substitution of Unstabilized Enolates Derived from α,β‐Unsaturated Ketones

We report Ir‐catalyzed, enantioselective allylic substitution reactions of unstabilized silyl enolates derived from α,β‐unsaturated ketones. Asymmetric allylic substitution of a variety of allylic carbonates with silyl enolates gave allylated products in 62–94 % yield with 90–98 % ee and >20:1 branched‐to‐linear selectivity. The synthetic utility of this method was illustrated by the short synthesis of an anticancer agent, TEI‐9826.     

Synthesis of Branched Alkylboronates by Copper‐Catalyzed Allylic Substitution Reactions of Allylic Chlorides with 1,1‐Diborylalkanes

Reported herein is a copper‐catalyzed S_N2′‐selective allylic substitution reaction using readily accessible allylic chlorides and 1,1‐diborylalkanes, a reaction which proceeds with chemoselective C?B bond activation of the 1,1‐diborylalkanes. In the presence of a catalytic amount of [Cu(IMes)Cl] [IMes=1,3‐bis(2,4,6‐trimethylphenyl)imidazole‐2‐ylidene] and LiOtBu as a base, a range of primary and secondary allylic chlorides undergo the S_N2′‐selective allylic substitution reaction to produce branched alkylboronates. The synthetic utilities of the obtained alkylboronates are also presented.     

Sequential Ir‐Catalyzed Allylation/2‐aza‐Cope Rearrangement Strategy for the Construction of Chiral Homoallylic Amines†

Sequential Ir‐catalyzed asymmetric allylation/2‐aza‐Cope rearrangement of arylidene aminomalonates with allylic carbonates was successfully developed, and a variety of enantioenriched homoallylic amine derivatives were obtained in high yields with good chirality transfer and excellent E/Z‐geometry control (up to 99% yield, 96% ee). Compared with previous dual catalytic system established for this transformation, the current mono metal catalytic system provides a simpler and more practical protocol employing the readily available starting materials.     

Simple palladium‐catalyzed C–N bond formation for poor nucleophilicity of aminonaphthalenes

Aromatic amines is not used commonly in allylic amination, presumably because of their less nucleophilic nature compared with the more extensively used benzylamine or relatively stable anionic nitrogen nucleophiles. An eco‐friendly method for C–O bond activation of allylic acetates using palladium associated with ligands in water leading to N‐allylation was described in this study. The palladium‐catalyzed allylic amination of allylic acetate with aminonaphthalenes gave 34–95% yields to the corresponding N‐allylic aminonaphthalenes. Copyright © 2011 John Wiley & Sons, Ltd.     

Dihydrobenzoxazines and tetrahydroquinoxalines by a tandem reduction‐reductive amination reaction

A tandem reduction‐reductive amination reaction has been applied to the synthesis of 3,4‐dihydro‐2H‐1,4‐benzoxazines and 1‐acetyl‐1,2,3,4‐tetrahydroquinoxalines. The nitroketones required for the benzoxazine ring closures were prepared by (A) alkylation of the anion derived from 2‐nitrophenol with an allylic halide or (B) nucleophilic aromatic substitution of an allylic alkoxide on 2‐fluoro‐1‐nitrobenzene followed by ozonolysis. Precursors for the quinoxalines were prepared by alkylation of the anion of 2‐nitroacetanilide with an allylic halide followed by ozonolysis. Catalytic hydrogenation of the nitroketones using 5% palladium‐on‐carbon in methanol then gave the target heterocycles by a reduction‐reductive amination sequence. The N‐methyl derivatives for both ring systems were easily prepared by adding 5‐10 equivalents of aqueous formaldehyde prior to the reduction. The dihydrobenzoxazines were isolated in high yield following purification by chromatographic methods; tetrahydroquinoxalines were isolated in a similar manner and possessed differentiated functionality on the two nitrogens.     

Chemo‐ and regioselective allylic oxidation: Oxo‐derivatives of 2‐phospholene sugar analogs

A convenient and facile chemo‐ and regioselective oxidation of the allylic methylene group in a 2‐phospholene ring system afforded the novel carbonyl derivatives of 2‐phospholenes ( 2a–i ). The method gives high conversion and selectivity in the formation of allylic ketones. The advantages of this oxidation method in such a five‐membered pseudo sugar 2‐phospholene ring are mentioned, and the oxidation is examined on several substituted 2‐phospholenes ( 1a–i ). © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:320–325, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10154     

Intramolecular Thioether Migration in the Rhodium‐Catalyzed Ene‐Cycloisomerization of Alkenylidenecyclopropanes by a Metal‐Mediated β‐Sulfide Elimination

Reported is the first example of a rhodium‐mediated β‐sulfide elimination, which represents a new mode of reactivity for late‐transition‐metal chemistry. This serendipitous discovery facilitates an ene‐cycloisomerization of allylic‐sulfide‐containing alkenylidenecyclopropanes (ACPs) to afford five‐membered carbo‐ and heterocyclic rings with concomitant intramolecular thioether migration. Interestingly, similar selectivity is obtained with both E‐ and Z‐allylic sulfides and the reaction is also feasible with an allylic selenide. Mechanistic studies are consistent with an inner‐sphere transfer of the sulfide, which is remarkable given the propensity for sulfides to poison transition‐metal catalysts. Finally, this type of atom‐economical rearrangement is envisioned to prompt the development of related processes given the utility of sulfides in target‐directed synthesis.     

Copper‐Catalyzed Enantioselective Allylic Alkylation with a γ‐Butyrolactone‐Derived Silyl Ketene Acetal

Herein, we report a Cu‐catalyzed enantioselective allylic alkylation using a γ‐butyrolactone‐derived silyl ketene acetal. Critical to the development of this work was the identification of a novel mono‐picolinamide ligand with the appropriate steric and electronic properties to afford the desired products in high yield (up to 96 %) and high ee (up to 95 %). Aryl, aliphatic, and unsubstituted allylic chlorides bearing a broad range of functionality are well‐tolerated. Spectroscopic studies reveal that a Cu^I species is likely the active catalyst, and DFT calculations suggest ligand sterics play an important role in determining Cu coordination and thus catalyst geometry.     

Enantioselective Synthesis of Pyrrole‐Based Spiro‐ and Polycyclic Derivatives by Iridium‐Catalyzed Asymmetric Allylic Dearomatization and Controllable Migration Reactions

The first highly diastereo‐ and enantioselective synthesis of five‐membered spiro‐2H‐pyrroles was achieved using an Ir‐catalyzed asymmetric allylic dearomatization reaction. The spiro‐2H‐pyrrole derivatives readily undergo a controllable and stereospecific allylic migration under acid catalysis, providing polycyclic pyrrole derivatives in excellent yields and ee values. Additionally, the novel Ir‐complex K1 , derived from [Ir(cod)Cl]₂ (cod=1,5‐cyclooctadiene) and N‐benzhydryl‐N‐phenyldinaphthophosphoramidite (BHPphos), showed excellent control of both diastereo‐ and enantioselectivities.