Understanding the 1,3-Dipolar Cycloadditions of Allenes

We have quantum chemically studied the reactivity, site-, and regioselectivity of the 1,3-dipolar cycloaddition between methyl azide and various allenes, including the archetypal allene propadiene, heteroallenes, and cyclic allenes, by using density functional theory (DFT). The 1,3-dipolar cycloaddition reactivity of linear (hetero)allenes decreases as the number of heteroatoms in the allene increases, and formation of the 1,5-adduct is, in all cases, favored over the 1,4-adduct. Both effects find their origin in the strength of the primary orbital interactions. The cycloaddition reactivity of cyclic allenes was also investigated, and the increased predistortion of allenes, that results upon cyclization, leads to systematically lower activation barriers not due to the expected variations in the strain energy, but instead from the differences in the interaction energy. The geometric predistortion of cyclic allenes enhances the reactivity compared to linear allenes through a unique mechanism that involves a smaller HOMO–LUMO gap, which manifests as more stabilizing orbital interactions.     

Preparation and Reactivity of 1,3-Bis(alkylthio)allenes and Tetrathiacyclic Bisallenes

Reactions of Ph(2)C(3) dianion, prepared from 1,3-diphenylpropyne and n-butyllithium, with alkyl thiocyanates or alkane dithiocyanates gave 1,3-bis(alkylthio)allenes 1 or tetrathiacyclic bisallenes 2, respectively. Thermal reactions of 1 gave thiophenes 4 and 7, benzothiepin 5, 1,2-bis(benzylidene)cyclobutane 6, thiete 8, and alpha,beta-unsaturated ketone 9, and the reactions of tetrathiacyclic bisallenes 2a gave a cyclic dimer, 1,2-bis(benzylidene)cyclobutane derivative 10, quantitatively. Irradiation of 1,3-bis(alkylthio)allenes 1 and tetrathiacyclic bisallenes 2a caused rearrangement to give alkynes 18, 20, and 21. In the irradiation of the cyclic bisallenes 2a, isomerizations from dl to meso and meso to dl isomers were also found. In the reactions of allenes 1 and cyclic bisallenes 2a with diphenyl diazomethane, the diazomethane reacted selectively with the double bond rather than with the sulfur atom.     

Synthesis and reactivity of allenes substituted by selenenyl groups at 1- and 3-positions

1,3-Bis(methylseleno)- and 1,3-bis(benzylseleno)-1,3-diphenylpropadienes were synthesized by reaction of Ph(2)C(3) dianion, prepared from 1,3-diphenylpropyne and n-butyllithium, with dimethyl diselenide or benzylselenocyanate in the presence of TMEDA, and reaction of the dianion with a mixture of dimethyl diselenide and benzylselenocyanate yielded 1-benzylseleno-3-methylselenoallene along with the symmetric allenes. Diselenocyclic allenes and tetraselenocyclic bisallenes were also obtained by reacting the dianion with corresponding alkane diselenocyanates. The thermal reaction of the 1,3-bis(alkylseleno)allenes mainly afforded enediynes through radical pathway, and the nine-membered cyclic allene provided intramolecular cyclization product via an intramolecular rearrangement. Heating of the cyclic bisallenes gave compounds derived from intramolecular cyclization products together with a small amount of the enediynes. Irradiation of allenes caused rearrangement of the selenenyl group to give alkynes, and the alkynes also reacted photochemically to yield the enediynes.     

Electronic effects in the regioselectivity of the singlet oxygen and 4-methyl-1,2,4-triazoline-3,5-dione ene reactions with isobutenylarenes

The regioselectivity of the ene pathway in the photooxidation of several 1-aryl-2-methylpropenes, as probed by stereoselective deuterium-labeling, depends on the electronic nature of the para phenyl-substituents. The reaction of the same array of alkenylarenes with 4-methyl-1,2,4-triazoline-3,5-dione (MTAD) gives ene products with an impressive >97% allylic hydrogen abstraction from the more substituted side of the alkene.     

An efficient synthesis of 2-vinylic cyclic 1,3-alkadienes via the Cp*Ru(II)-catalyzed intermolecular coupling reactions of alkynes and cyclic allenes

2-Vinylic cyclic 1,3-alkadienes can be obtained with moderate to good yields via the Cp*RuCl(PPh3)2-catalyzed coupling reaction of alkynes with cyclic allenes.     

1,2-Didehydro[10]annulenes: structures, aromaticity, and cyclizations

The conformational space of C(10)H(8) 1,2-didehydro[10]annulenes, along with their unimolecular conversion to isonaphthalenes (cyclic allenes), has been studied computationally using DFT (B3LYP), single-reference [CCSD(T)], and multireference (MCQDPT2) post-HF methods. The introduction of the linear alkynyl moiety releases enough angle strain to make a nearly planar "heart" aromatic form the preferred conformer by more than 6 kcal/mol [CCSD(T)] over a localized C(2) "twist" structure, as opposed to the closely related C(10)H(10) [10]annulene system. Computations also show that electrocyclic ring-opening of isonaphthalenes to the heart C(10)H(8) annulene takes place through a low barrier of 15 kcal/mol, and this should be considered the working mechanism for the reported isomerizations during dehydro Diels-Alder reactions of phenylacetylenes.     

Low-temperature photosensitized oxidation of a guanosine derivative and formation of an imidazole ring-opened product

An organic-soluble guanosine derivative, 2',3',5'-O-(tert-butyldimethylsilyl)guanosine (1), was prepared and its photosensitized oxidation was carried out in several solvents at various temperatures. Singlet oxygen is the reactive oxidizing agent responsible for this reaction. Neither an endoperoxide nor a dioxetane intermediate was detected by low-temperature NMR even at -78 degrees C. A product (A) with an oxidized imidazole ring was the only major product detected at room temperature; this compound could be isolated by low-temperature column chromatography and was characterized by (1)H and (13)C and mass spectroscopy. CO(2) was the other major product. A small amount of the corresponding 8-oxo-7,8-dihydroguanosine derivative B was detected during the initial stage of the photooxidation and was shown to be intermediate in the formation of two products of extensive degradation, C and D. Reaction of 1 with the singlet oxygen analogues 4-methyl-1,2,4-triazoline-3,5-dione (MTAD) and 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) gave products consistent with a proposed mechanism involving the rearrangement of an initially formed endoperoxide to give A and B from reaction of 1 with singlet oxygen.     

Cyclic allene intermediates in intramolecular dehydro Diels-Alder reactions: labeling and theoretical cycloaromatization studies

A comprehensive theoretical and experimental investigation of dehydro Diels-Alder reactions examining the evolution of the cyclic allene intermediates under conditions for intramolecular and ionic and radical intermolecular cycloaromatization processes is reported. Theoretical calculations showed that the most favored intramolecular path for cycloaromatization of 1,2,4-cyclohexatriene 4 and its benzoannulated derivative 14, strained cyclic allenes, consists of a pair of successive [1,2] H shifts rather than a [1,5] shift. Cycloaromatization of cyclic allenes may follow both inter- and intramolecular pathways, depending on the experimental conditions (use of protic or aprotic solvents). For synthetic purposes, the best procedure is to use a protic solvent to promote the ionic intermolecular route, the fastest and highest yielding. When the reaction is carried out in CCl4, intermolecular radical addition of chlorine to the cyclic allene competes with intramolecular aromatization paths. Theoretical calculations predict a low barrier for the reaction of cyclic allenes with carbon tetrachloride, and that the cyclic allenes act as nucleophiles in this reaction.     

Novel Mg-organic reagents in organic synthesis. Cp2TiCl2 catalyzed intermolecular cyclomagnesiation of cyclic and acyclic 1,2-dienes using Grignard reagents

High-yield (>80%) catalytic intermolecular cyclomagnesiation of cyclic and acyclic allenes with the aid of Grignard reagents has been realized in the presence of Cp₂TiCl₂. The synthesized unsaturated bi- and tricyclic organomagnesium compounds (OMC) have been successfully converted in situ into thiophenes, unsaturated ketones, cyclic and acyclic hydrocarbons with high regio- and stereoselectivity.     

Aluminum carbenoids in allene cyclopropanation

The reactions of aluminum carbenoids with alkyl- and phenyl-substituted allenes and cyclic allenes are studied. An efficient method for the synthesis of substituted spiropentanes was developed. 1,2-Cyclononadiene was selectively converted into bicyclo[7.1.0]dec-1-ene. An unusual transformation of α-methylphenylallene into a spiroindane derivative under the action of Et₃Al-CH₂I₂ was found.     

Gold-catalyzed intermolecular hydroalkoxylation of allenes; difference in mechanism between hydroalkoxylation and hydroamination

A wide range of alcohols 2 react with various allenes 1 in the presence of ClAuPPh₃/AgOTf catalyst at ambient temperature without solvent to produce allylic ethers 3. Contrary to the hydroamination, which proceeds through high chiral-face selectivity for chiral allenes to give the corresponding chiral allylic amines, transfer of chirality is not observed in the hydroalkoxylation, suggesting that the mechanism of the gold-catalyzed hydroalkoxylation is different from that of hydroamination.     

A novel and highly efficient two-carbon ring expansion

[reaction: see text]. Dynamic gas-phase thermoisomerization (DGPTI) of medium- and large-ring 3-vinylcycloalkanones at 600-630 degrees C produces isomeric gamma,delta-unsaturated cycloalkanones expanded by two carbon atoms. A reaction mechanism involving an open-chain diradical intermediate, followed by intramolecular recombination under insertion of the vinyl group is proposed. Substituents on the vinyl moiety are transferred locospecifically to the ring-expanded ketones as corresponding beta- and gamma-substituents, respectively. The preparation of extraordinary cyclic allenes can be accomplished by DGPTI (540 degrees C) of 3-ethinylcyclododecanone.     

Regiospecific Functionalization of Cyclic Allenes with Catecholeorane

Reaction of diborane¹ and disiamylborane² with cyclic allenes, resulted in the formation of a mixture of products resulting from the addition of boron at the central carbon as well as terminal carbon. Fish has reported that addition of 4, 4, 6-trimethyl-1, 3, 2-dioxaborinane to 1, 3-disubstituted allenes takes place at the central carbon atom preferentially when the hydroboration was done at 130° for 35–50 h in a sealed tube.³ The reactivity and stability of catecholborane at high temperatures which is known to provide greater stearic     

To bend or not to bend! The dilemma of allenes

Allenes, though expected to be linear, are found to be bent in many examples, especially in the case of cyclic allenes. The bending of allene is attributed to the weakening of π-bond strength across the allene. However, tetrakis(dimethylamino)allene {((CH(3))N)(2)C═C═C(N(CH(3))(2))}, which is characterized by push-push interactions, has been shown to be linear, thus leading to doubts of the current understanding of the bent allenes. In this article, we report the ab initio MO/DFT, NBO based electronic structure analysis of R(2)C═C═CR(2) (R = H, NH(2)) with a gradual increase in the number of amino substituents. The results indicate that the allenic π-bond strength and bending potential decrease, with an increase in the amino substitution. Molecular orbital analysis provides necessary clues regarding the delicate balance between orthogonality of the π orbitals and the p orbitals on the central carbon, which dictates the bending potential of the allenes. The dilemma of to bend or not to bend is a unique feature of tetraaminoallenes (NH(2))(2)C═C═C(NH(2))(2) in comparison to isoelectronic heteroallenes (NH(2))(2)C═N═C(NH(2))(2)(+) and (NH(2))(2)C═B═C(NH(2))(2)(-).     

Palladium-catalyzed asymmetric silaboration of allenes

An enantioselective silaboration of allenes was achieved using an achiral silylborane in the presence of a palladium catalyst bearing a chiral monodentate phosphine ligand. (R)-2-Bis(3,5-dimethylphenyl)phosphino-1,1'-binaphthyl gave the highest enantioselectivities in the addition of (diphenylmethylsilyl)pinacolborane to the internal C=C bond of terminal allenes at 0 degrees C, giving the corresponding beta-borylallylsilanes in high yields with high enantiomeric excesses. The enantioselectivity depended on the bulkiness of substituents of allenes: the enantiomeric excesses were found to be 91-93% ee (R = tert- and sec-alkyl), 88-90% ee (R = aryl), and 80-82% ee (R = prim-alkyl and Me) at 0 degrees C. Perfect chirality transfer was observed in the intramolecular cyclization reactions of the functionalized allylsilanes, affording highly enantioenriched cyclic alkenylboranes, which underwent Suzuki-Miyaura coupling with aryl halides.     

Highly regio- and stereoselective acylboration, acylsilation, and acylstannation of allenes catalyzed by phosphine-free palladium complexes: an efficient route to a new class of 2-acylallylmetal reagents

A new method for the synthesis of substituted 2-acylallylmetal reagents in a highly regio- and stereoselective fashion involving a three-component assembly of allenes, acyl chlorides, and bimetallic reagents (B-B, Si-Si, and Sn-Sn) catalyzed by phosphine-free palladium complexes is described. Treatment of various allenes (CR(2)R(3)=C=CH(2)) with acyl chlorides (R(1)COCl) and bispinacolatodiboron in the presence of PdCl(2)(CH(3)CN)(2) in toluene at 80 degrees C gave 2-acylallylboronates in moderate to good yields. The acylsilation of allenes with acid chlorides and hexamethyldisilane (5) proceeded successfully in the presence of Pd(dba)(2) in CH(3)CN affording the corresponding allylsilanes (CR(2)R(3)=C(COR(1))CH(2)SiMe(3)) in good to moderate yields. Several chloroformates (R(4)OCOCl) also react with 1,1-dimethylallene (2a) and 5 to afford allylsilanes (CR(2)R(3)=C(COOR(4))CH(2)SiMe(3)) in 66-70% yields. Acylstannation of allenes could also be achieved by slow addition of hexabutylditin (10) to the reaction mixture of acyl chloride (or chloroformate) and allene 2a in CH(3)CN in the presence of Pd(dba)(2) at 60 degrees C; the corresponding 2-substituted allylstannanes were isolated in moderate to good yields. The above catalytic reactions are completely regioselective and highly stereoselective. A mechanism is proposed to account for the catalytic reactions and the stereochemistry.     

Diels-alder reactivity of vinylsulfoxyallenes

Vinylsulfoxyallenes 3a-c are prepared from propargylic alcohols in 47-65% yield. Vinylsulfoxyallenes undergo facile [4 + 2] cycloadditions with methyl triazolidenedione (MTAD) and singlet oxygen to afford phenylsulfinylpyridazines and spirocyclic phenylsulfinyl-2H-pyran-3(6H)-ones in excellent yields (60-90%). Spirocyclic phenylsulfinyl-2H-pyran-3(6H)-ones are oxidized to the corresponding phenylsulfones with peracid or can be epoxidized with basic hydrogen peroxide. Spirocyclic pyranone formation is thought to proceed via the rearrangement of a labile cyclic peroxide intermediate 14.     

Photosensitized oxidative deprotection of oximes to their corresponding carbonyl compounds by platinum(II) terpyridyl acetylide complex

Platinum(II) terpyridyl acetylide complex (1) photosensitizes the oxidation of aldoximes 2-4, aliphatic acyclic and cyclic ketoximes 5-7, and aromatic ketoximes 8-10 into their corresponding carbonyl compounds with good to excellent yields in acetonitrile solution. This deprotection of oximes proceeds via singlet oxygen ((1)O(2)) mechanism. The photosensitizer can be easily separated from the product and unreacted starting material by extraction with ethyl acetate and reused for photooxidation without loss of (1)O(2)-generation capacity.     

Hydroindation of allenes and its application to radical cyclization

Hydroindation of allenes and radical cyclization of 1,2,7-trienes (allenenes) were accomplished by HInCl2 with high regioselectivity to afford a variety of cyclic compounds. The resulting vinylic indiums could be used for successive coupling reactions in a one-pot procedure. The use of HInCl2 generated slowly in situ is extremely effective for the radical cyclization.     

Strain estimates for small-ring cyclic allenes and butatrienes

Isodesmic and homodesmic equations at the B3LYP/6-311+G(d,p)+ZPVE level of theory have been used to estimate strain for the homologous series of cyclic allenes and cyclic butatrienes. A simple fragment deformation approach also has been applied and appears to work better for the larger rings. For the cyclic allene series, estimates for allene functional group strain (kcal/mol) include: 1,2-cyclobutadiene, 65; 1,2-cyclopentadiene, 51; 1,2-cyclohexadiene, 32; 1,2-cycloheptadiene, 14; 1,2-cyclooctadiene, 5; 1,2-cyclononadiene, 2; 1,2,4-cyclohexatriene, 34; and bicyclo[3.2.1]octa-2,3-diene, 39. For cyclic butatrienes, functional group strain estimates include: 1,2,3-cyclobutatriene, >100; 1,2,3-cyclopentatriene, 80; 1,2,3-cyclohexatriene, 50; 1,2,3-cycloheptatriene, 26; 1,2,3-cyclooctatriene, 17; and 1,2,3-cyclononatriene, 4. Barriers to interconversion of enantiomers in cyclic allenes are reduced with increasing strain. Newly predicted values include: 1,2-cyclopentadiene <1 kcal/mol and bicyclo[3.2.1]octa-2,3-diene, 7.4 kcal/mol. Estimated levels of strain parallel the known reactivity of these substances.