An interesting issue of Diels-Alder selectivity discovered en route to 11-O-debenzoyltashironin

The hypervalent iodine-mediated oxidative dearomatization/Diels-Alder cascade was examined in the context of the natural product 11-O-debenzoyltashironin. Interestingly, the regioselectivity of the Diels-Alder reaction can be completely switched by changing the dienophile. Trapping of allyl alcohols during the oxidative dearomatization gives rise to the five-membered acetal, while trapping of allenyl alcohols results in the six-membered acetal. [reaction: see text]     

Highly Regio‐ and Stereoselective Synthesis of β‐Phenyl‐chalcogenyl Allyl Sulfones by Hydrochalcogenation Reaction of 1,2‐Allenyl Sulfones

The hydrochalcogenation of allenyl sulfones with sodium organyl chalcogenolates can proceed smoothly to give β‐phenylchalcogenyl allyl sulfones in high yields with exclusive regioselectivity. For the asymmetric allenyl sulfone, the reaction has both high regio‐ and stereoselectivity with the predominace of E‐isomer. Some applications of β‐phenyltelluro and β‐phenylselanyl allyl sulfone in organic synthesis are also investigated.     

Intramolecular Diels-Alder Reaction of Furans with Allenyl Ethers Followed by Phenylthio and Trialkylsilyl Groups Rearrangement

A new reaction involving an intramolecular Diels-Alder reaction of a furan diene with an allenyl ether dienophile followed by phenylthio group rearrangement was discovered. Treatment of the propargyl ethers 2a-c with t-BuOK in t-BuOH at 85 ° C gave the phenylthio group rearrangement products 5a-c and 6a-c . A reaction involving an intramolecular Diels-Alder reaction of a furan diene with an allenyl ether dienophile followed by trialkylsilyl group rearrangement is also demonstrated.     

Intramolecular Diels-Alder reaction of 2-diphenylphosphinyl-5-(propargyloxymethyl)furans followed by nucleophilic 1,2-rearrangement of the phosphinyl group

The base-catalyzed intramolecular Diels-Alder reactions of 2-diphenylphosphinyl-5-(propargyloxymethyl)furans 2a-e gave the tetrahydrofuran ring annulated o-diphenylphosphinophenols 3a-e in 70-80% yields, a novel reaction involving an intramolecular Diels-Alder reaction of furan diene with allenyl ether dienophile followed by a nucleophilic 1,2-rearrangement of the diphenylphosphinyl group.     

On the Diels-Alder reactions of pentadienyl maleates and citraconates

Reactions between conjugated dienols and maleic anhydride provide either cis-fused or trans-fused bicyclic products as major products, depending upon how the reaction is carried out. Simply mixing the two reactants together generally leads to cis-fused lactone acids in thermal reactions which proceed viaintermolecular Diels-Alder reaction followed by intramolecular esterification. Pre-forming the maleate half ester derivative followed by heating affords predominantly trans-fused lactone acids in good yields by way of an intramolecular Diels-Alder (IMDA) reaction. Sorbyl citraconate half esters undergo a rapid thermolytic fragmentation in refluxing toluene to form the dienol and citraconic anhydride. The resulting diene-dienophile pair undergo an intermolecular cycloaddition followed by a rapid intramolecular esterification to give cis-fused bicyclic lactone acids as major products. The IMDA reaction of citraconic half esters is sufficiently rapid in DMSO to dominate over fragmentation: the exo-cycloadduct is formed almost exclusively. Nine literature reports of endo-selective IMDA reactions of triene acids are erroneous; the cycloadditions proceed in an intermolecular manner.     

Practical Stannylation of Allyl Acetates Catalyzed by Nickel with Bu3SnOMe

A practical and scalable nickel‐catalyzed allylic stannylation of allyl acetates with Bu₃SnOMe is described. A variety of acyclic and cyclic allyl acetates, even with base‐sensitive moieties, undergoes the stannylation by using NiBr₂/4,4′‐di‐tert‐butylbipyridine (dtbpy)/Mn catalyst system to afford highly functionalized allyl stannanes with excellent regioselectivity and yields. Furthermore, the scope of protocol is also extended by the reaction of propargyl acetates, giving rise to propargyl or allenyl stannanes. Additionally, a unique diastereoselectivity using the nickel catalyst different from the palladium was demonstrated for the stannylation of cyclic allyl acetates. In the reaction, inexpensive and stable nickel complexes, abundant reductant (Mn), and atom‐economical stannyl source were used.     

Synthetic studies toward GKK1032s, novel antibiotic antitumor agents: enantioselective synthesis of the fully elaborated tricyclic core via an intramolecular Diels-Alder cycloaddition

An enantioselective synthesis of the fully elaborated tricyclic decahydrofluorene core (ABC-ring system) of GKK1032s, novel antimicrobial and antitumor agents, has been accomplished for the first time by employing a highly diastereoselective intramolecular Diels-Alder (IMDA) reaction. The key substrate for the IMDA reaction was efficiently prepared through (i) an intermolecular Diels-Alder reaction between a siloxydiene and an optically active enone derived from D-mannitol to construct the appropriately functionalized C-ring and (ii) CuCl-promoted Stille coupling of an (E)-vinyl iodide and a vinylstannane to install the requisite triene side chain as the crucial steps.     

Synthetic studies of GKK1032s: the asymmetric synthesis of the decahydrofluorene skeleton via a novel cyclization of silyl enol ether and sequential retro Diels-Alder and intramolecular Diels-Alder reactions

GKK1032s, which were isolated from the culture broth of Penicillium sp. GKK1032, exhibit antitumor activity. We constructed the fully elaborated decahydrofluorene skeleton of GKK1032s. The C-ring was constructed by intramolecular cyclization reaction between a chiral epoxide and silyl enol ether, and the dienophile moiety was introduced concurrently. In addition, the AB-rings were stereoselectively constructed using novel sequential retro Diels-Alder (DA) and intramolecular Diels-Alder (IMDA) reactions. Several further modifications of the IMDA adduct were carried out, leading to the asymmetric synthesis of the desired hydroxyester including nine stereo centers.     

A novel and facile stereocontrolled synthetic method for polyhydro-quinolines and pyridopyridazines via a diene-transmissive Diels-Alder reaction involving inverse electron-demand hetero Diels-Alder cycloaddition of cross-conjugated azatrienes

Cross-conjugated azatrienes bearing an electron-withdrawing sulfonyl or benzoyl group on the nitrogen atom underwent, on heating or in the presence of a Lewis acid (TMSOTf), an initial inverse electron-demand hetero Diels-Alder reaction with electron-rich dienophiles (vinyl ether, vinyl thioether, and allenyl ether) to produce 1:1 cycloadducts with high endo selectivity. The initial cycloadducts thus obtained underwent a second Diels-Alder reaction stereoselectively on the newly formed diene unit with electron-deficient dienophiles to give the crossed bis-cycloadducts, octahydroquinolines, with high diastereo-π-facial selectivity. The N-sulfonylazatrienes tethering an ortho-cinnamyloxyphenyl dienophile at the triene terminal underwent an initial intramolecular hetero Diels-Alder reaction of the inverse electron-demand type. The subsequent second Diels-Alder reaction of the formed mono-cycloadducts completed the diene-transmissive hetero Diels-Alder protocol to give benzopyrano[3,4-c]quinolines in a highly stereoselective manner.     

金属单质锡促进的水相中醛的Barbier类型炔丙基化反应

报道了一种简单、 高效且快速的醛的炔丙基化反应体系. 使用廉价的金属单质锡粉, 在路易斯酸SnCl₂·2H₂O促进下, 实现了水相中醛羰基化合物的Barbier类型炔丙基化反应, 高收率、高区域选择性地得到单一的高炔丙基醇产物(收率99%). 该方法具有底物适用范围广、反应条件温和(30℃)、环境友好(以水为介质)及反应速度快(30 min内反应原料基本消失)等优点. 另外, 在使用肉桂醛为底物且将反应温度升至55℃时, 意外地得到了中等收率的新型高度对称的烯炔醚化合物.     

Selective C-C bond formation between alkynes mediated by the [RuCp(PR)(3)](+) fragment leading to allyl,butadienyl, and allenyl carbene complexes--an experimental and theoretical study

The reaction of alkynes with [RuCp(PR(3))(CH(3)CN)(2)]PF(6) (R=Me, Ph, Cy) affords, depending on the structure of the alkyne and the substituent of the phosphine ligand, allyl carbene or butadienyl carbene complexes. These reactions involve the migration of the phosphine ligand or a facile 1,2 hydrogen shift. Both reactions proceed via a metallacyclopentatriene complex. If no alpha C[bond]H bonds are accessible, allyl carbenes are formed, while in the presence of alpha C[bond]H bonds butadienyl carbenes are typically obtained. With diphenylacetylene, on the other hand, a cyclobutadiene complex is formed. A different reaction pathway is encountered with HC[triple bond]CSiMe(3), ethynylferrocene (HC[triple bond]CFc), and ethynylruthenocene (HC[triple bond]CRc). Whereas the reaction of [RuCp(PR(3))(CH(3)CN)(2)]PF(6) (R=Ph and Cy) with HC[triple bond]CSiMe(3) affords a vinylidene complex, with HC[triple bond]CFc and HC[triple bond]CRc this reaction does not stop at the vinylidene stage but subsequent cycloaddition yields allenyl carbene complexes. This latter C[bond]C bond formation is effected by strong electronic coupling of the metallocene moiety with the conjugated allenyl carbene unit, which facilitates transient vinylidene formation with subsequent alkyne insertion into the Ru[double bond]C bond. The vinylidene intermediate appears only in the presence of bulky substituents of the phosphine coligand. For the small R=Me, head-to-tail coupling between two alkyne molecules involving phosphine migration is preferred, giving the more usual allyl carbene complexes. X-ray structures of representative complexes are presented. A reasonable mechanism for the formation of both allyl and allenyl carbenes has been established by means of DFT calculations. During the formation of allyl and allenyl carbenes, metallacyclopentatriene and vinylidene complexes, respectively, are crucial intermediates.     

Intramolecular carbostannation reaction of active methine compounds with an unactivated C-C pi-bond mediated by SnCl(4)-Et(3)N

In the presence of SnCl(4) and Et(3)N, intramolecular carbostannation reaction of various active methine compounds having an unactivated alkenyl, alkynyl, or allenyl group proceeds in good yields with complete regioselectivity. The subsequent reaction of the resulting Sn intermediates with some electrophiles provides functionalized cyclopentane and cyclohexane derivatives.     

Scope of the allylation reaction with [RuCp(PP)]+ catalysts: changing the nucleophile or allylic alcohol

The scope of the dehydrative allylation reaction using allyl alcohol as allyl donor with [RuCp(PP)]⁺ complexes as catalysts is explored. Aliphatic alcohols are successfully allylated with allyl alcohol or diallyl ether, obtaining high selectivity for the alkyl allyl ether. The reactivity of aliphatic alcohols is in the order of primary > secondary ? tertiary. The tertiary alcohol 1‐adamantanol reacts extremely slowly in the absence of strong acid, but when HOTs is added, reasonable yields of 1‐adamantyl allyl ether are obtained. The alkyl allyl ether is found to be the thermodynamically favored product over diallyl ether. Apart from alcohols, thiols and indole are also efficiently allylated, while aniline acts as a catalyst inhibitor. Allylation reactions with various substituted allylic alcohols give products with retention of the substitution pattern. It is proposed that a Ru(IV) σ‐allyl species plays a key role in the mechanism of these allylation reactions. Copyright © 2010 John Wiley & Sons, Ltd.     

Unusual Cycloadducts from the Dipolar Cycloaddition of Allenyl Perfluoroalkyl Sulfones to Nitrones

The dipolar cycloaddition reaction of allenyl perfluoroalkyl sulfones （1） to nitrones （2） was described. Unlike nonfluorine-containing allenyl sulfones, 1 reacted readily with 2 in ether at room temperatttre and unusual zwitterionic cycloadducts （3） were obtained in good yields due to the strong electron-withdrawing effect of perfluoroalkyl groups. The structure of 3 was characterized by spectral analyses and X-ray crystallography.     

Exploring an expedient IMDA reaction approach to construct the guanacastepene core

Construction of the [5-7-6] tricyclic core of guanacastepenes was attempted by using the intramolecular Diels-Alder (IMDA) reaction and Me(3)Al-mediated ring opening of the oxabridge as key synthetic steps. The illustrated chemistry demonstrated a synthetic feasibility to build up the framework of guanacastepenes by the IMDA reaction. [reaction: see text]     

Enhancing the scope of the Diels-Alder reaction through isonitrile chemistry: emergence of a new class of acyl-activated dienophiles

α,β-Unsaturated imides, formylated at the nitrogen atom, comprise a new and valuable family of dienophiles for servicing Diels-Alder reactions. These systems are assembled through extension of recently discovered isonitrile chemistry to the domain of α,β-unsaturated acids. Cycloadditions are facilitated by Et(2)AlCl, presumably via chelation between the two carbonyl groups of the N-formyl amide. Applications of the isonitrile/Diels-Alder logic to the IMDA reaction, as well as methodologies to modify the N-formyl amide of the resultant cycloaddition product, are described. It is expected that this easily executed chemistry will provide a significant enhancement for application of Diels-Alder reactions to many synthetic targets.     

Unexpected epimerization and stereochemistry revision of IMDA adducts from sorbate-related 1,3,8-nonatrienes

Intramolecular Diels-Alder (IMDA) reaction of two sorbate-related 1,3,8-nonatrienes has been investigated in MeCN at 180 °C for 1.5 h under controlled microwave heating. On checking the crude product mixture before purification, partial epimerization of the major adduct was found during the reaction. After column chromatographic purification over silica gel, only two cis adducts were obtained and their structures have been thoroughly established by X-ray crystallographic analysis. It is concluded that the putative major trans adduct predicted by the IMDA reaction mechanism undergoes facile epimerization at high temperature or in the presence of silica gel. Structural revision on the adducts has been made.     

From allene to allene: a palladium-catalyzed approach to beta-allenyl butenolides and their application to the synthesis of polysubstituted benzene derivatives

An allene to allene protocol for the synthesis of beta-allenyl butenolides in moderate to high yields from 2,3-allenoic acids and propargylic carbonates catalyzed by Pd(OAc)2-TFP has been developed; the products were applied successfully to the Diels-Alder reaction with electron-deficient alkynes to afford polysubstituted benzene derivatives with an excellent regioselectivity.     

Synthesis of polycyclic structures by the Diels-Alder reaction of inner-outer-ring 1,3-bis(trimethylsilyloxy)dienes

A Diels-Alder reaction of novel inner-outer-ring 1,3-silyloxydienes 5-8 with a variety of dienophiles to afford highly functionalized polycyclic structures is reported. The inner-outer-ring 1,3-silyloxydienes 5-8 containing five- to seven-membered carbocyclic and heterocyclic rings were prepared in a single reaction vessel from 2-acetylcyclocarbonyls in quantitative yields. The Diels-Alder reaction with 1,4-benzoquinone (BQ), dimethyl acetylenedicarboxylate (DMAD), and methyl vinyl ketone (MVK) proceeded smoothly at room temperature, affording functionalized polycyclic naphthols, phenols, and enones with high regioselectivity and good yields (39-75%). Moreover, dienes 5-8 also reacted in a hetero-Diels-Alder reaction with benzaldehyde (BA) and N-benzylideneaniline (NBA) in the presence of catalytic amounts of ZnCl2, affording substituted polycyclic pyranones and pyridinones in good yields (40-93%). Overall, our synthetic strategy provides straightforward access to an interesting set of polycyclic structures useful for natural and nonnatural product synthesis.     

Bridged to Fused Ring Interchange. Methodology for the Construction of Fused Cycloheptanes and Cyclooctanes. Total Syntheses of Ledol, Ledene, and Compressanolide

The type two intramolecular Diels-Alder reaction (T2IMDA) is an efficient method for the formation of medium rings. The methodology is particularly effective for the construction of seven- and eight-membered rings. A strategy for the synthesis of functionalized cycloheptanes and cyclooctanes has been developed that involves a bridged to fused ring interchange. The T2IMDA provides a synthesis for rigid bridged bicyclic molecules that can be stereoselectively elaborated before ozonolysis of the bridgehead double bond. Following oxidative cleavage, aldol condensation provides fused bicyclic ring systems that otherwise are difficult to synthesize. This methodology is amenable to the synthesis of terpene natural products. This is demonstrated here through total syntheses of (+/-)-ledol and (+/-)-ledene and a formal synthesis of (+/-)-compressanolide.