Mono and double polar [4 + 2(+)] Diels-Alder cycloaddition of acylium ions with O-heterodienes

Gas-phase reactions of acylium ions with alpha,beta-unsaturated carbonyl compounds were investigated using pentaquadrupole multiple-stage mass spectrometry. With acrolein and metacrolein, CH(3)-C(+)(double bond)O, CH(2)(double bond)CH-C(+)(double bond)O, C(6)H(5)-C(+)(double bond)O, and (CH(3))(2)N-C(+)(double bond)O react to variable extents by mono and double polar [4 + 2(+)] Diels-Alder cycloaddition. With ethyl vinyl ketone, CH(3)-C(+)(double bond)O reacts exclusively by proton transfer and C(6)H(5)-C(+)(double bond)O forms only the mono cycloadduct whereas CH(2)(double bond)CH-C(+)(double bond)O and (CH(3))(2)N-C(+)(double bond)O reacts to great extents by mono and double cycloaddition. The positively charged acylium ions are activated O-heterodienophiles, and mono cycloaddition occurs readily across their C(+)(double bond)O bonds to form resonance-stabilized 1,3-dioxinylium ions which, upon collisional activation, dissociate predominantly by retro-addition. The mono cycloadducts are also dienophiles activated by resonance-stabilized and chemically inert 1,3-dioxonium ion groups, hence they undergo a second cycloaddition across their polarized C(double bond)C ring double bonds. (18)O labeling and characteristic dissociations displayed by the double cycloadducts indicate the site and regioselectivity of double cycloaddition, which are corroborated by Becke3LYP/6-311++G(d,p) calculations. Most double cycloadducts dissociate by the loss of a RCO(2)COR(1) molecule and by a pathway that reforms the acylium ion directly. The double cycloadduct of the thioacylium ion (CH(3))(2)N-C(+)(double bond)S with acrolein dissociates to (CH(3))(2)N-C(+)(double bond)O in a sulfur-by-oxygen replacement process intermediated by the cyclic monoadduct. The double cycloaddition can be viewed as a charge-remote type of polar [4 + 2(+)] Diels-Alder cycloaddition reaction.     

On the 1,3-dipolar cycloaddition reactions of indenone with N-N-C dipoles: density functional theory calculations

Density functional theory (DFT) calculations at the B3LYP/6-311G* theoretical level have been performed to study the 1,3-dipolar cycloaddition (1,3-DC) reactions between indenone (1) and different 1,3-dipoles (diazomethane and N-methyl C-methoxy carbonyl nitrilimine, compounds 2 and 3, respectively). The geometrical and energetic properties were analysed for the different reactives, transition states and cycloadducts formed (compounds 4-11). The reactions proceed in the gas-phase by an asynchronous concerted mechanism, yielding different regiochemistry dependent on the 1,3-dipole chosen, although with dipole 3 some degree of synchrony was found in the formation of cycloadduct 5. The 1,3-DC between 1 and 3 was regioselective, being the cycloadduct 11 favoured against 9. The NMR chemical shift parameters (GIAO method) were also calculated for the reactives and cycloadducts.     

Diastereoselective and intramolecular cycloadditions of asymmetric p-nitroso phosphine oxides

Benzyl phenyl P-nitroso phosphine oxide (5) reacts as an N-O heterodienophile with 1,3-cyclopentadiene to give the diastereomeric cycloadducts 6a,b in a ratio of 1.5:1 (6a:6b). The same reaction in the presence of tin tetrachloride produces 6a,b in a ratio of 2.9:1 (6a:6b). Cycloaddition of the structurally modified P-nitroso phosphine oxide (18) with 1,3-cyclopentadiene forms the diastereomeric cycloadducts 16a,b in a ratio of 3.1:1 (16a:16b). These results suggest the reactions of these P-nitroso phosphine oxides and 1,3-cyclopentadiene occur through a transition state where the heterodienophile adopts an s-cis conformation and approaches the diene in an exo fashion syn to the phenyl group. This model resembles those proposed for the cycloadditions of the structurally similar asymmetric vinyl phosphine oxides. Reaction of 18 with 1,3-cyclopentadiene in the presence of a Lewis acid produces cycloadducts 16a,b in a ratio of 7:1 (16a:16b), which approaches synthetic utility. Similar experiments show that 1,3-cyclohexadiene likely reacts with P-nitroso phosphine oxides through a different transition state, limiting current predictions regarding the diastereoselectivity of these reactions. The intramolecular cycloaddition of an asymmetric P-nitroso phosphine oxide (19) for the first time produces a unique phosphorus-containing heterocyclic compound (20).     

Synthesis and some cycloaddition reactions of 2-(triisopropylsilyloxy)acrolein

[reaction: see text]2-(Triisopropylsilyloxy)acrolein is easily prepared by the reaction of triisopropylsilyl triflate and 2-methoxy-2-methyl-[1,3]dioxan-5-one in the presence of triethylamine. This dienophile reacts with selected dienes in the presence of catalytic amounts of scandium triflate to afford products that are formally 4 + 3 cycloadducts. An exception is seen in the case of butadiene, where only a 4 + 2 cycloadduct is observed.     

Poly- und spirocyclische Silylhydrazone – Synthese und Molekülstrukturen

Poly- and Spirocyclic Silylhydrazones — Synthesis and Molecular Structures Bulky aminotrifluorosilanes react with lithiated dimethylketone-hydrazone to give 1,2-diaza-3-sila-5-cyclopentenes — DSCP — ( 1, 2 ). The 4-silylated ( 3–5, 8–15 ) and siloxysilyl-substituted ( 17, 18 ) rings eliminate no halosilane or siloxane thermally. Lithiated 2 dimerises with LiF elimination to give the (2+2)cycloadduct of a 1,2-diaza-3-sila-3,5-cyclopentadiene ( 6 ). Lithiated DSCP reacts with MeSiF₂N(CMe₃)SiMe₂CMe₃ via a nucleophilic 1,3-methanide ion migration to form LiF and the spirocyclic compound 18 . A compound with spirocyclic silicon ( 21 ) is formed in the reaction of bis(1,2-diaza-3-sila-5-cyclopenten-4-yl)difluorosilane ( 19 ) and the lithium salt of dimethyl-ketone-tert-butylhydrazone. The crystal structures of 6 and 21 are reported.     

Some novel aspects of regioselectivity in 1,3 dipolar cycloadditions of 4h-1-benzopyran-4-thione

4H-1-Benzopyran-4--thio)ie (1) reacted smoothly with nitrilimines (3a-e) to afford regioselectiue cycloadducts (4a-X) in good yields. In contrast, benzonitrile oxide (6) and aldonitrones (7a-d) reacted preferentially at the thione function. The unstable cycloadduct (B) or (9) ruptured to give as isolable products chromone (10) and phenyl isothiocyanate (11) and the tnioamides (12a-d). This indirectly proves the site of attack of the dipole at the thione group.     

New reactions and step economy: the total synthesis of (±)-salsolene oxide based on the type II transition metal-catalyzed intramolecular [4+4] cycloaddition

Studies on the viability of the type II nickel-catalyzed intramolecular [4+4] cycloaddition of bis-dienes show that it is influenced by both diene substitution and geometry. Both E- and Z-isomers of 19 and 20 react, albeit at markedly different rates, to afford cycloadducts, whereas only the Z-isomer of 9 (and not the E-isomer) reacts to give 8 and 25. Chemoselective elaboration of 8 to (±)-salsolene oxide (7) was used to confirm the cycloadduct structure while establishing a step economical route to the natural product.     

Novel [4 + 2]-cycloaddition of 1-phenyl-1-benzothiophenium salts with dienes. Experimental evidence for a lack of aromaticity in the thiophene ring

The [4 + 2]-cycloaddition reaction of 1-phenyl-1-benzothiophenium triflates has been conducted for the first time. [4 + 2]-Cycloaddition with dienes such as cyclopentadiene and 1,3-diphenylisobenzofuran occurs successfully to give cycloadducts. This result indicates that the C=C bond of the thiophene ring acts as a 2pi electron component in the cycloaddition reaction. Cycloadducts were formed in high yields with high stereoselectivity. However, the cycloaddition with other less reactive dienes such as 2,3-dimethyl-1,3-butadiene did not take place. The structure and stereochemistry of cycloadduct 2a were analyzed by NMR techniques. Furthermore, reaction of the cycloadducts with sodium methoxide in methanol gave the ring-opened products in high yields.     

1,3-Dipolar Cycloadditions to Strained Olefins

The Bredt olefins bicyclo [3.3.1]non-1-ene (2) , bicyclo [4.2.1]non-1 (8)-ene (3) , and bicyclo [4.2.1]non-1 (2)-ene (4) react rapidly with 1,3-dipoles such as diazomethane, phenyl azide, and mesitonitrile oxide to yield mixtures of two regioisomeric cycloadducts 10, 11 and 12 , respectively. On the contrary, cycloaddition to the comparable monocyclic 1-methyl-(E)-cyclooctene (5) is fairly regioselective. 2-Methylnorborn-2-ene (6) gives one isomer with mesitonitrile oxide (as do less strained olefins), but mixtures with diazomethane and phenyl azide. ¹H-NMR. and ¹³C-NMR. spectra of the cycloadducts are reported. The results are discussed in the light of frontier molecular orbital theory.     

Addition reactions of cyclooctatetraene with 1,3-diphenylisobenzofuran the benzene ring as dienophile in a [4+2] cycloaddition reaction

Addition reactions of cyclooctatetraene with 1,3-diphenylisobenzofuran resulted in the formation of three 1:1 cycloadducts, 1, 2, and 3, and a 1:2 cycloadduct, 4. Single crystal x-ray analysis established 3 to be a cage compound formed by an unprecedented [4+2] cycloaddition reaction of 1 in which the double bond of the benzene moiety acted as the dienophile.     

Electrocyclic Reactions of Siloles: A Combined Experimental and Theoretical Study

The reaction of 4‐chloro‐1,2‐dimethyl‐4‐supersilylsila‐1‐cyclopentene ( 2 a ) with Li[NiPr₂] at ?78 °C results in the formation of the formal 1,4‐addition product of the silacyclopentadiene derivative 3,4‐dimethyl‐1‐supersilylsila‐1,3‐cyclopentadiene ( 4 a ) with 2,3‐dimethyl‐4‐supersilylsila‐1,3‐cyclopentadiene ( 5 a ). In addition the respective adducts of the Diels–Alder reactions of 4 a + 4 a and 4 a + 5 a were obtained. Compound 4 a , which displays an s‐cis‐silacyclopentadiene configuration, reacts with cyclohexene to form the racemate of the [4+2] cycloadduct of 4 a and cyclohexene ( 9 ). In the reaction between 4 a and 2,3‐dimethylbutadiene, however, 4 a acted as silene as well as silacyclopentadiene to yield the [2+4] and [4+2] cycloadducts 10 and 11 , respectively. The constitutions of 9 , 10 , and 11 were confirmed by NMR spectroscopy and their crystal structures were determined. Reaction of 4‐chloro‐1,2‐dimethyl‐4‐tert‐butyl‐4‐silacyclopent‐1‐ene ( 2 c ) with KC₈ yielded the corresponding disilane ( 12 ), which was characterized by X‐ray crystal structure analysis (triclinic, P$\bar 1$ ). DFT calculations are used to unveil the mechanistic scenario underlying the observed reactivity.     

The cycloaddition of the 1,3-butadiene radical cation with acrolein and methyl vinyl ketone

The 1,3-butadiene radical cation reacts with acrolein and methyl vinyl ketone to produce ‘stable’ adducts. The nature of the reaction and the structures of the adducts were investigated by collisional activation decomposition (CAD) combined with tandem mass spectrometry (MS/MS), and also by Fourier transform mass spectrometry. The CAD spectra of gas-phase adducts were compared with those of suitable model compounds. On that basis, it was determined that the 1,3-butadiene radical cation undergoes a cycloaddition with these α,β-unsaturated carbonyl compounds. The butadiene radical cation serves as the ‘ene’, and the acrolein and methyl vinyl ketone react as dienes, forming cycloadducts having 2-ethenyl-2,3-dihydropyran radical cation structures.     

New Studies on [2+3] Cycloadditions of Thermally Generated N‐Isopropyl‐ and N‐(4‐Methoxyphenyl)‐Substituted Azomethine Ylides

The thermal reaction of 1‐substituted 2,3‐diphenylaziridines 2 with thiobenzophenone ( 6a ) and 9H‐fluorene‐9‐thione ( 6b ) led to the corresponding 1,3‐thiazolidines (Scheme 2). Whereas the cis‐disubstituted aziridines and 6a yielded only trans‐2,4,5,5‐tetraphenyl‐1,3‐thiazolidines of type 7 , the analogous reaction with 6b gave a mixture of trans‐ and cis‐2,4‐diphenyl‐1,3‐thiazolidines 7 and 8 . During chromatography on SiO₂, the trans‐configured spiro[9H‐fluorene‐9,5′‐[1,3]thiazolidines] 7c and 7d isomerized to the cis‐isomers. The substituent at N(1) of the aziridine influences the reaction rate significantly, i.e., the more sterically demanding the substituent the slower the reaction. The reaction of cis‐2,3‐diphenylaziridines 2 with dimethyl azodicarboxylate ( 9 ) and dimethyl acetylenedicarboxylate ( 11 ) gave the trans‐cycloadducts 10 and 12 , respectively (Schemes 3 and 4). In the latter case, a partial dehydrogenation led to the corresponding pyrroles. Two stereoisomeric cycloadducts, 15 and 16 , with a trans‐relationship of the Ph groups were obtained from the reaction with dimethyl fumarate ( 14 ; Scheme 5); with dimethyl maleate ( 17 ), the expected cycloadduct 18 together with the 2,3‐dihydropyrrole 19 was obtained (Scheme 6). The structures of the cycloadducts 7b, 8a, 15b , and 16b were established by X‐ray crystallography.     

Stepwise acid-promoted double-Michael process: an alternative to Diels-Alder cycloadditions for hindered silyloxydiene-dienophile pairs

The hindered diene 1 reacts with 3-methylcyclohexenone 6 catalyzed by triflimide to produce the Mukaiyama Michael product 7 (low-temperature quenching) or the [4+2] cycloadduct 8 (quenching at 0 degrees C). Reaction of the hindered diene 23 with 2-methylcyclohexenone 12 with 5:1 AlBr3:AlMe3 afforded a 71% yield of a 1.9:1 mixture of two cycloadducts. Hydrolysis of the major isomer gave the dione 27', a model for the BCD ring system of pentacyclic triterpenes. [reaction: see text].     

Intramolecular cycloaddition of O-tert-butyldimethylsilyloximes in the presence of BF3 x OEt2

[reaction: see text] Intramolecular cycloaddition of novel 1,3-dipoles, N-boranonitrones, was examined. Treatment of O-tert-butyldimethylsilyloximes 9-12 having olefin moieties with 2 equiv of BF3 x OEt2 generated N-boranonitrones, which underwent intramolecular cycloaddition to afford N-nonsubstituted cycloadducts 16 (and/or 18) after extractive workup. Despite the Lewis-acidic conditions, the olefin geometry of the substrates was retained in the cycloadducts in the present cycloaddition. The electronic nature of the N-boranonitrones appeared to be electrophilic. In the case of substrate 11c, having an electron-donating methyl group at an internal position of the olefin moiety, the cycloaddition gave the bridged cycloadduct 18b. The cycloaddition proceeded at relatively low temperature, and the diastereoselectivity was high.     

Cycloaddition behavior of 3,4-diazacyclopentadienone dioxides toward bicyclo[2.2.1]heptadiene derivatives. X-ray analysis of the cycloadduct and reaction pathway

The cycloaddition behavior of 2,5-disubstituted 3,4-diazacyclopentadienone dioxide 1a-c toward epoxy-naphthalene ( 2a ) and norbornadiene ( 2b ) was investigated. The structures of the products were determined on the basis of the ¹H- and ¹³C-nmr spectral data and the X-ray analysis data. The stereospecific formation of the endo-exo 1,3-dipolar cycloadducts from 2a indicates that the cycloadduct resulted from the direct 1,3-dipolar cycloaddition. The cycloaddition behavior of 1 toward 2 is discussed on the basis of the PM3-calculated transition-state structures.     

Organometallic synthons: The wittig reaction of tricarbonyl [(3,4,5,6-η)-1,3,5-cycloheptatriene-1-carboxaldehyde] iron

The utility of the Wittig reaction in synthesis of organometallic compounds is exemplified by its application to the preparation of a series of tetraene—Fe(CO)₃ complexes from aldehyde 9 and a variety of triphenylphosphoranes. Reaction of 9 with triphenylmethylene phosphorane afforded unexpectedly a $\text{1}\text{1}$ isomeric mixture of 8-methylheptafulveneiron tricarbonyl (12), probably via a (1,9) hydrogen shift of intermediate 11. Triphenylbenzylidene phosphorane condensed with 9 to give the cis and trans isomers of cycloheptatrienyl—styrene complex 14. The triphenylphosphoranes of carbomethoxymethylene, carboethoxymethylene and cyanomethylene react with 9 yielding the appropriate trans condensation products exclusively. Tetracyanoethylene (TCNE) and N-phenyltriazolinedione (NPTD) readily react periselectively with the unrearranged Wittig reaction products at the free diene moiety, affording the corresponding 4+2 cycloadducts. Heptafulvene complex 12, upon reaction with TCNE, gave the 8+2 cycloadduct 26.     

Exploring the Border between Concerted and Two‐Step Pathways of 1,3‐Dipolar Cycloadditions of Organic Azides to Cyclic Ketene N,X‐Acetals. – Synthesis and 15N‐NMR Spectra of Zwitterions and Spirocyclic Cycloadducts

Cyclic ketene N,X‐acetals 1 are electron‐rich dipolarophiles that undergo 1,3‐dipolar cycloaddition reactions with organic azides 2 ranging from alkyl to strongly electron‐deficient azides, e.g., picryl azide ( 2L ; R¹=2,4,6‐(NO₂)₃C₆H₂) and sulfonyl azides 2M – O (R¹=XSO₂; cf. Scheme 1). Reactions of the latter with the most‐nucleophilic ketene N,N‐acetals 1A provided the first examples for two‐step HOMO(dipolarophile)–LUMO(1,3‐dipole)‐controlled 1,3‐dipolar cycloadditions via intermediate zwitterions 3 . To set the stage for an exploration of the frontier between concerted and two‐step 1,3‐dipolar cycloadditions of this type, we first describe the scope and limitations of concerted cycloadditions of 2 to 1 and delineate a number of zwitterions 3 . Alkyl azides 2A – C add exclusively to ketene N,N‐acetals that are derived from 1H‐tetrazole (see 1A ) and 1H‐imidazole (see 1B , C ), while almost all aryl azides yield cycloadducts 4 with the ketene N,X‐acetals (X=NR, O, S) employed, except for the case of extreme steric hindrance of the 1,3‐dipole (see 2E ; R¹=2,4,6‐(^tBu)₃C₆H₂). The most electron‐deficient paradigm, 2L , affords zwitterions 16D , E in the reactions with 1A , while ketene N,O‐ and N,S‐acetals furnish products of unstable intermediate cycloadducts. By tuning the electronic and steric demands of aryl azides to those of ketene N,N‐acetals 1A , we discovered new borderlines between concerted and two‐step 1,3‐dipolar cycloadditions that involve similar pairs of dipoles and dipolarophiles: 4‐Nitrophenyl azide ( 2G ) and the 2,2‐dimethylpropylidene dipolarophile 1A (R, R=H, ^tBu) gave a cycloadduct 13 H , while 2‐nitrophenyl azide ( 2 H ) and the same dipolarophile afforded a zwitterion 16A . Isopropylidene dipolarophile 1A (R=Me) reacted with both 2G and 2 H to afford cycloadducts 13G , J ) but furnished a zwitterion 16B with 2,4‐dinitrophenyl azide ( 2I) . Likewise, 1A (R=Me) reacted with the isomeric encumbered nitrophenyl azides 2J and 2K to yield a cycloadduct 13L and a zwitterion 16C , respectively. These examples suggest that, in principle, a host of such borderlines exist which can be crossed by means of small structural variations of the reactants. Eventually, we use ¹⁵N‐NMR spectroscopy for the first time to characterize spirocyclic cycloadducts 10 – 14 and 17 (Table 6), and zwitterions 16 (Table 7).     

Dual behavior of masked o-benzoquinones in intermolecular Diels-Alder reactions with acyclic dienes: a rapid entry to polyfunctionalized bicyclo[2.2.2]oct-5-en-2-ones and cis-decalins

The potentiality of the masked o-benzoquinones, i.e., 6,6-dimethoxy-2,4-cyclohexadienones 5-8, to react both as dienes and dienophiles in their intermolecular reactions has been demonstrated. The masked o-benzoquinones (MOBs) 5-8 generated in situ from 2-methoxyphenols 1-4 underwent intermolecular Diels-Alder cycloadditions with acyclic 1,3-dienes 9a-e to provide bicyclo[2.2.2]octenones 10a-f-13a-f along with cis-decalin derivatives 14a-f-17a-f with regio- and stereoselectivity, except in the case of MOB 8. The formation of cis-decalins in these Diels-Alder reactions illustrates the dienophilic character of MOBs, in addition to their general behavior as dienes. The ratio of the two cycloadducts obtained in each reaction as a result of the dual character of MOBs depends on the nature and/or position of the substituents on both the cyclohexadienone moiety and the added conjugated acyclic diene. All of the cycloadducts resulted from the diene property of MOBs in intermolecular Diels-Alder reactions smoothly underwent Cope rearrangement to furnish cis-decalins as sole products in excellent to quantitative yields.     

Further studies of the thermal and photochemical diels-alder reactions of N-methyl-1,2,4-triazoline-3,5-dione (MeTAD) with naphthalene and some substituted naphthalenes

MeTAD thermally reacted with naphthalene (2) and methylated naphthalenes to give equilibrium mixtures of starting materials and [4 + 2] cycloadducts. Methyl substitution on the naphthalene ring generally increased both the amount of cycloadduct formed and the rate of cycloaddition relative to 2. The isolated cycloadducts were all thermally labile and quantitatively reverted to the parent naphthalene in the presence of 2,3-dimethyl-2-butene as a trap for liberated MeTAD. The rates of the cycloreversion reactions were affected by substitution patterns but not appreciably by solvent. A mechanism for the cycloaddition reaction is presented that proposes the involvement of a charge-transfer complex. Photochemically, MeTAD demonstrated lower regioselectivity in its reactions with substituted naphthalenes relative to the corresponding thermal reactions.