Allenic Esters Research Articles

Synthesis of quaternary carbon centered chromans from the reactions of ethyl 2-(2-hydroxyaryl)-2-oxoacetates with allenic ester or allenic sulfone catalyzed by tertiary phosphine and SPTS

Cyclization reactions of ethyl 2-(2-hydroxyaryl)-2-oxoacetates with ethyl 2,3-butadienoate and allenylsulfone proceeded smoothly in the presence of tertiary phosphine and sodium p-toluenesulfinate (SPTS) to give the corresponding quaternary carbon centered chromans in moderate to good yields under mild conditions, which provides an alternative efficient approach for the synthesis of biologically active chroman products.

Silver(I)-Catalyzed Tandem 1,3-Acyloxy Migration/Mannich-type Addition/Elimination of the Sulfonyl Group of N-Sulfonylhydrazone-propargylic Esters to 5,6-Dihydropyridazin-4-one Derivatives

The addition of nucleophiles to C=N bonds offers a highly efficient synthetic strategy for accessing nitrogen-containing molecules.1 Among the well-developed addition reactions, such as the highly efficient Mannich reaction, various C-H bond-activated compounds including carboxylic acid derivatives, nitroalkanes, and terminal alkynes have been applied as nucleophiles to achieve different classes of amines.2 However, employing new nucleophiles without activated C-H bonds, such as internal alkynes and allenic esters are limited when using metal catalysts.3 Herein, we wish to report a new addition of allenic esters to C=N bonds initiated by a silver-catalyzed 1,3-migration of propargylic esters.

Synthesis and cytotoxic evaluation of substituted 3-(3′-indolyl-/3′-pyridyl)-isoxazolidines and bis-indoles

Regio- and stereoselective 1,3-dipolar cycloadditions of C-(3-indolyl)-N-phenylnitrone (10) were carried out with different mono-substituted, disubstituted and cyclic dipolarophiles under mono-mode microwave irradiation to obtain substituted 3-(indol-3′-yl)-N-phenyl-isoxazolidines (16–22). Reactions of nitrone (10) with allenic esters under similar conditions afforded, via a domino process, bis-indole derivatives (23a–c) along with compounds 24 and 25. Similarly, reactions of C-(3-pyridyl)-N-phenylnitrone (26) with mono-substituted, disubstituted and cyclic dipolarophiles were carried out in refluxing dry toluene to obtain substituted 3-(3′-pyridyl)-N-phenylisoxazolidines (27–34). Some of the compounds (16f, 18b, 23a, 23c, 27c and 29f) display significant cytotoxicity against a number of human cancer cell lines.

DABCO-catalyzed regioselective cyclization reactions of β,γ-unsaturated α-ketophosphonates or β,γ-unsaturated α-ketoesters with allenic esters

Highly efficient DABCO-catalyzed [4 + 2] cycloaddition of β,γ-unsaturated α-ketophosphonates or β,γ-unsaturated α-ketoesters with allenic esters gives the corresponding highly functionalized tetrahydropyran and dihydropyran derivatives in good to excellent yields and moderate to good regioselectivities under mild conditions.

Synthesis of optically active dihydropyrans from asymmetric [4 + 2] cycloaddition of β,γ-unsaturated α-ketoesters with allenic esters

β-Isocupreidine (β-ICD) catalyzed asymmetric [4 + 2] cycloaddition of β,γ-unsaturated α-ketoesters with allenic esters afforded ester-substituted functionalized dihydropyran derivatives in high yields along with high enantioselectivities under mild conditions.

Construction of adjacent spiro-quaternary and tertiary stereocenters through phosphine-catalyzed asymmetric [3+2] annulation of allenoates with alkylidene azlactones

A novel axially chiral spiro-phosphine-catalyzed highly regio-, diastereo- and enantioselective [3+2] cycloaddition of alkylidene azlactones with various allenic esters has been developed, affording the corresponding functionalized spirocyclic products in moderate to excellent yields under mild conditions. These spirocyclic products as masked amino acids can be easily transformed into aspartic amino acid analogues.

Development of a Formal Catalytic Asymmetric [4 + 2] Addition of Ethyl-2,3-butadienoate with Acyclic Enones

Allene esters are unique not only as excellent electrophiles but also because of their ability for subsequent reactivity after the initial nucleophilic attack. A mechanistically inspired cyclization using ethyl-2,3-butadienoate and acyclic enones to provide dihydropyrans in excellent yields and enantioselectivity under solvent-free conditions at room temperature is reported.

Triazole–Au(I) complex as chemoselective catalyst in promoting propargyl ester rearrangements

Triazole–Au (TA–Au) catalysts were employed in several transformations involving propargyl ester rearrangement. Good chemoselectivity was observed, which allowed the effective activation of the alkyne without affecting the reactivity of the allene ester intermediates. These results led to the investigation of the preparation of allene ester intermediates with TA–Au catalysts under anhydrous conditions. As expected, the desired 3,3-rearrangement products were obtained in excellent yields (generally >90% yields with 1% loading). Besides the typical ester migrating groups, carbonates and carbamates were also found to be suitable for this transformation, which provided a highly efficient, practical method for the preparation of substituted allenes.

Quinidine derived organocatalysts for the nucleophile promoted asymmetric [4+2] cycloaddition reaction of salicyl N-tosylimine with allenic esters

Cinchona alkaloid derived catalyst cat. 5 prepared from β-isocupreidine (β-ICD) was found to be a fairly effective organocatalyst for the nucleophilic promoted asymmetric [4+2] cycloaddition reaction of salicyl N-tosylimines and allenic esters to give the corresponding adducts in up to 80% yield, 87% ee.

Phosphine-Catalyzed [3+2] Cyclizations: Applications to the Enantioselective Synthesis of Cyclopentene-Fused Chromanones and Dihydroquinolinones

Phosphine-promoted [3+2] cyclizations of allenic esters or phosphonates with coumarin derivatives were used to synthesize functionalized bicyclo[4.3.0]chroman-2-ones. Analogous bicy­clo[4.3.0]quinolinones were similarly prepared by a two-step strategy involving a phosphine-catalyzed [3+2] cyclization of diethyl propadienylphosphonate and 3-(2-nitrophenyl)acrylate as the key step. Enantiomerically enriched compounds, with enantiomeric excesses in the range 70-86%, were obtained by using (S,S)-Ferro­PHANE as the chiral catalyst for the cyclization step.

Chemistry of Heterocyclic Ketene Aminals: Construction of Imidazo(pyrido)[1,2-a]pyridines and Imidazo(pyrido)[3,2,1-ij][1,8]naphthyridines via DABCO-Catalyzed Tandem Annulations

2-(2-Chloroaroyl)methyleneimidazolidines with four reactive sites show fascinating structural features and could be used as a new strategy for the synthesis of novel heterocycles. This paper presents our new findings in the reaction of 2-(2-chloroaroyl)methyleneimidazolidines with allenic esters affording functionalized imidazo(pyrido)[1,2-a]pyridines via DABCO-catalyzed tandem annulations. Of particular significance is the incorporation of an o-halo group into the aryl ring of 2-benzoylmethylene-imidazolidines to set up a convenient and general way for constructing unusual imidazo(pyrido)[3,2,1-ij][1,8]naphthyridines.

Enantioselective iridium-catalyzed vinylogous Reformatsky-aldol reaction from the alcohol oxidation level: linear regioselectivity by way of carbon-bound enolates.

Enantioselective iridium-catalyzed vinylogous Reformatsky-aldol reaction from the alcohol oxidation level: linear regioselectivity by way of carbon-bound enolates.

ChemInform Abstract: Synthetic and Stereochemical Studies Directed Towards Anatoxin-a.

The synthesis and stereocontrolled AgI-catalysed cyclisation of a series of allenic amino esters 8a–e is described. For compounds 8a–d the cis-2,5-disubstituted pyrrolidine 9 is formed exclusively but the primary amine 8e undergoes cyclisation nonselectively to give a mixture of cis- and trans-pyrrolidines 9e and 10e. The synthetic potential of this allene-based methodology has been illustrated by the conversion of compound 8avia9a into (±)-anatoxin-a 1 and the methoxy phosphine oxides 18 and 19 have been studied as ketone homologating agents within this context. The enzymatic resolution of (±)-8a using chymotrypsin is also described.

ChemInform Abstract: Photoaddition of Benzophenone to Allenic Esters.

Abstract Photochemical addition of benzophenone to ethyl-penta-2, 3-dienoate ( 1a ), ethyl hexa-2,3-dienoate ( 1b ) and ethyl 4-methylhexa-2,3-dienoate ( 1c ) furnish various mono- and dioxetanes. Novel oxetanes ( 2a,b ) result in the reactions of ( 1a,b ) through addition of benzophenone to electron deficient C2-C3 π-bond of the respective esters. A rationalization of the obtained modes of photoaddition has been offered.

Stereoselective formation of tertiary and quaternary carbon centers via inverse conjugate addition of carbonucleophiles to allenic esters

Stereoselective inverse conjugate addition of carbonucleophiles to allenoates bearing a chiral auxiliary in the ester moiety afforded optically active α,β-unsaturated carboxylic esters bearing a new stereocenter at the δ position. The rationalization of the observed selectivity was supported by semi-empirical molecular orbital calculations.

ChemInform Abstract: Iron Carbenoid Mediated Ylide Reactions

AbstractReview: 35 refs.

ChemInform Abstract: Stereoselective Total Synthesis of the Pseudopterolide Kallolide A.

A total synthesis of the pseudopterolides, kallolide A (36) and kallolide A acetate (35), has been achieved. The racemic forms were prepared from the syn adduct 20 of furan 13 and stannane 17 (BF(3).OEt(2)-promoted addition) via the 15-membered propargylic allylic ether 25. [2,3]Wittig ring contraction led to the cis, anti, cis product 26. Alcohol 26 was transformed to butenolide 34 with net retention of configuration by Pd(PPh(3))(4)-catalyzed carbonylation of the mesylate 27 and ensuing AgNO(3)-catalyzed cyclization of the derived allenic acid 29. Solvolysis of the SEM ether (at C2) 34 in acetic acid or aqueous t-BuOH afforded racemic kallolide A acetate (35) and kallolide A (36), respectively, with inversion of stereochemistry by an S(N)1 process. Key elements of stereocontrol, including the steric outcome of the [2,3]Wittig ring contraction, the allenic ester isomerization, and the solvolysis reactions, were predicted from molecular mechanics calculations. The C8 and C2 epimers 45 and 46 of the cis, anti, cis kallolide A SEM ether precursor 34 were also prepared. The synthetic route originated from the anti adduct 19 of aldehyde 13 and the allylic chloride 16 and CuCl (cat), HSiCl(3), and i-Pr(2)NEt. Adduct 19 was subjected to the same sequence as the syn counterpart 20 to produce the trans, anti, cis [2,3]Wittig ring contraction product 42. The derived allenoate 44 afforded a 1:1 mixture of butenolides 45 and 46 upon sequential treatment with TBAF and AgNO(3). Finally, the natural enantiomer (+)-36 of kallolide A was synthesized from the enantioenriched syn adduct (+)-20, prepared by addition of allylic stannane 17 to aldehyde 13 promoted by a modified chiral acyloxyborane Lewis acid.

ChemInform Abstract: A Convenient Synthesis of 4-Phenylchalcogeno Allenic Esters from α-(Phenylchalcogeno)acid Chlorides.

Abstract The reaction of ethyl 2-(triphenylphosphoranylidene) acetate or propionate 3a–b with α-chalcogeno ketenes generated in situ by the reaction of α-chalcogeno acid chlorides 1–2 with triethylamine in dichloromethane gives moderate to good yields of 4-phenylchalcogeno allenic esters 4. The corresponding 4-phenylseleno allenic esters 4a–e were obtained in isolated yields of 60 to 93%, while 4-phenylthio allenic esters 4f–j were obtained in isolated yields of 74 to 93%.

Studies on the asymmetric, phosphine-promoted [3+2] annulations of allenic esters with 2-aryl-1,1-dicyanoalkenes

The first enantioselective variant of the phosphine-promoted [3+2] cycloaddition reaction between allenoates and 2-aryl-1,1-dicyanoethylenes has been developed. The use of ( S)- t-butyl-Binepine as the chiral organocatalyst allows the synthesis of functionalized cyclopentenes with both aryl and heteroaryl substituents on the stereogenic carbon, in high yields and ees of up to 95%.

Diastereoselective Aza‐Baylis–Hillman Reactions: Synthesis of Chiral α‐Allenylamines and 2‐Azetines from Allenic Esters

AbstractThe reactivity of allenic esters towards activated N‐sulfonylimines in the presence of DABCO was explored. A formal [2+2] cycloaddition of benzyl buta‐2,3‐dienoate and N‐arylidenebenzenesulfonamides yielded mainly 2‐methyleneazetidines. Interestingly, a DABCO‐catalysed reaction of 2,3‐allenoates, bearing a chiral auxiliary on the ester moiety, with N‐arylidenebenzenesulfonamides led to optically active aza‐Baylis–Hillman products and 2‐azetine derivatives.