Carbonylative cycloadducts

Hydroxy-THISs react with electron-deficient alkynes to give nonisol-able adducts that extrude carbonyl sulfide, affording pyrroles (23). Compound 16 (X = 0) seems particularly reactive (Scheme 16) (25). The cycloaddition to benzyne yields isoindoles in low- yield. Further cyclo-addition between isoindole and benzyne leads to an iminoanthracene as the main product (Scheme 17). The cycloadducts derived from electron-deficient alkenes are stable (23, 25) unless highly strained. Thus the two adducts, 18a (R = H, R = COOMe) and 18b (R = COOMe, R = H), formed from 7, both extrude furan and COS under the reaction conditions producing the pyrroles (19. R = H or COOMe) (Scheme 18). Similarly, the cycloadduct formed between 16 (X = 0) and dimethylfumarate... 

Hydroxy-THISs add regioselectively to the C=N bonds of isocyanates or isothiocyanates. The initially formed cycloadducts eliminate carbonyl sulfide with formation of 4-hydroxy- or 4-mercaptoimidazolium hydroxide inner salts (21) (Scheme 21). 4-Hydroxyimidazolium hydroxide... 

Introduction of an additional methyl group on the donor atom of TMM moiety gives a low 33% yield of the perhydroindans (49, X=H2) and (50, X=H2) with substantial production of the diene by-products [24]. However, it is still remarkable that the reaction works at all since the corresponding intermolecular cycloaddition failed. Incorporation of a carbonyl moiety adjacent to the donor carbon atom doubles the yield of the cycloadducts to 66% (Scheme 2.15). This so-called acyl effect works by making the donor carbon of the TMM unit "softer," thus facilitating the initial step of the conjugate addition, as well as inhibiting base-induced side reactions [22]. 

TMM cycloadditions to cyclic and conjugated ketones have also been reported (Scheme 2.22) [31]. The steric nature of the substrate does play a critical role in determining product formation. Thus the cyclic ketone (73) produced 55% yield of the tetrahydrofuran, but no cycloadduct could be obtained from the cyclic ketone (74). The enone (75) gave only carbonyl cycloaddition, whereas enone (76) yielded only olefin adduct. Interestingly, both modes of cycloaddition were observed with the enone (77). The ynone (78) also cycloadds exclusively at the carbonyl function [34]. 

The Lewis acid-catalyzed 1,3-dipolar cycloaddition reaction of nitrones to a,/ -un-saturated carbonyl compound in the presence of Lewis acids has been investigated by Tanaka et al. [31]. Ab-initio calculations were performed in a model reaction of the simple nitrone 18 reacting with acrolein 1 to give the two cycloadducts 19 and 20 (Scheme 8.7). 

Reaction of the dihydropyranyl-substituted complex 83 with a conjugated internal alkynone 84 affords the Dotz-type formal [3+2+1] cycloadduct 86 in only 6% yield. The major product is the tricycle 85 as the result of a formal [3+4+1] cycloaddition with incorporation of the ynone carbonyl group (Scheme 18) [77]. 

Scheme 2.7). The phenols were formed during isolation (chromatography on silica gel) from the corresponding cycloadducts. In the reaction with p-benzoquinone, a product was unexpectedly obtained from a hetero-T>ie s-Alder reaction with the quinone acting as a carbonyl dienophile. 

Azadienes undergo Diels-Alder reactions to form pyridine, dihydro- and tetrahydropyridine derivatives. N-Vinyl lactim ethers undergo Diels-Alder reactions with a limited set of dienophiles. " Thioketones react with dienes to give Diels-Alder cycloadducts. The carbonyl group of lactams have also been shown to be a dienophile. Certain heterocyclic aromatic rings (among them furans) can also behave as dienes in the Diels-Alder reaction. Some hetero dienes that give the reaction are -C=C-C=0, 0=C-C=0, and N=C-C=N. ... 

The reaction of 9 (generated thermally from 7 in toluene) with tetraphenyl-cyclopentadienone is more complex. Both the [6 + 2]-cycloadduct 3416), for which an X-ray structure analysis is available, and the [12 + 2]-cycloadduct 3516), whose constitution has been assigned primarily on the basis of H-NMR evidence, are obtained. The two cycloadducts presumably have a common intermediate which, in accord with the general reactivity of 9, should possess betaine character (.31 - 32) it is caused by nucleophilic attack by the carbonyl oxygen atom on the phosphorus of the heterocumulene. Ring closure of the carbanionic carbon atom... 

These authors also prepared novel epoxy-bridged cyclooxaalkanones in this process, the carbonyl group always acts as 1,3-dipolarophile, even if one employs ct,(3-unsaturated aldehydes. Thus, reaction of 6/2-16 with aliphatic or aromatic aldehydes 6/2-17 in the presence of catalytic amounts of rhodium acetate gave 6/2-18, regioselectively. With the a, 3-unsaturated aldehydes 6/2-20, only cycloadducts 6/2-21 were obtained using the diazo compound 6/2-19 as substrate (Scheme 6/2.3) [191]. 

Tetracyano ethylene oxide, however, which represents a potential 1,3-dipole of the carbonyl ylide type, reacts with diphenyl cyclopropenone to give a cycloadduct of probable structure 415/417263, which may arise from insertion into the cyclopropenone C1(2)/C3 bond. 

Oxetanes are the cycloadducts from a carbonyl compound and an olefin. This one step photochemical formation of a four membered ring heterocycle has been named the Paterno-Buchi reaction 489a> b). Oxetanes are important synthetic intermediates as they can fragment into the carbonyl-olefin pair by which they were not formed (a so termed carbonyl-olefin metathesis). Two examples of such oxetan cracking reactions are shown below in (4.76)490) and in (4.77)491) in this last example the oxetane was used as a precursor for the pheromone E-6-nonenol,... 

Other aromatic heterocycles undergo Patemo-Btichi reaction with carbonyl compounds, although these reactions have seldom been applied to organic synthesis. For example, thiophene reacts cleanly with benzaldehyde to afford a single exo product in 63% yield87. Pyrroles also react with aldehydes and ketones however, as a result of the lability of the presumed initial cycloadducts, the only products isolated, even with the rigorous exclusion of acid, are the 3-hydroxyalkylpyrroles 200 (equation 7)89. 

Extensively developed by Ojima and co-workers, SiCaT and carbonylative silylcarbocyclization (CO-SiCaC) represent a rapid entry into polycyclic molecules of interest.271 For instance, the rhodium-catalyzed intramolecular SiCaT of triyne 441 afforded tricyclic compound 442 in high yield, accompanied by a small amount of cycloadduct 443 (Scheme 111).270... 

The utility of bis(oxazoline)-Cu(II) complexes as catalysts for the Diels-Alder reaction has been examined in a number of other systems. Aggarwal et al. (205) demonstrated that a-thioacrylates behave as effective two-point binding substrates for these catalysts. With cyclopentadiene, catalyst 271d induces the reaction at -78°C to provide the cycloadduct in 94 6 diastereoselectivity and >95% ee. Aggarwal proposes that the metal binds to the carbonyl oxygen and to the sulfur atom. The sulfur substituent is placed opposite the ligand substituent thereby shielding the bottom face of the alkene. Considerably lower selectivities are observed with 5-Me substrates. 

Allenyltrimethylsilanes add to ethyl glyoxalate in the presence of a chiral pybox scandium triflate catalyst to afford highly enantioenriched homopropargylic alcohols or dihydrofurans, depending on the nature of the silyl substituent (Tables 9.39 and 9.40) [62]. The trimethylsilyl-substituted silanes give rise to the alcohol products whereas the bulkier t-butyldiphenylsilyl (DPS)-substituted silanes yield only the [3 + 2] cycloadducts. A bidentate complex of the glyoxalate with the scandium metal center in which the aldehyde carbonyl adopts an axial orientation accounts for the observed facial preference ofboth additions. 

Allenamides are more stable and hence easier to handle in synthetic manipulations [152], When allenamide 187 was heated with 2equiv. of acrolein or methyl vinyl ketone (MVK), cycloadducts were isolated as single regioisomers. Allenamides containing either an oxazolidinone or imidazolidinone moiety also reacted with these a,/1-unsaturated carbonyl compounds under thermal conditions. 

Catalyst 329, prepared from trimethylaluminum and 3,3/-bis(triphenylsily 1)-1,1 /-bi-2-naphthol, allowed the preparation of the endo cycloadduct (2S )-327 with 67% ee. The use of non-polar solvents raised the ee, but lowered the chemical yield213. Recently, it was reported that the reaction to form 327 exhibited autoinduction when mediated by catalyst 326214. This was attributed to a co-operative interaction of the cycloadduct with the catalyst, generating a more selective catalytic species. A wide variety of carbonyl ligands were tested for their co-operative effect on enantioselectivity. Sterically crowded aldehydes such as pivaldehyde provided the best results. Surprisingly, 1,3-dicarbonyl compounds were even more effective than monocarbonyl compounds. The asymmetric induction increased from 82 to 92% ee when di(l-adamantyl)-2,2-dimethylmalonate was added while at the same time the reaction temperature was allowed to increase by 80 °C, from -80 °C to 0°C. 

Dienes do not react with carbonyl compounds unless the latter are activated by electron-withdrawing substituents such as carboxyl groups. Cyclohexa-1,3-diene, for example, adds diethyl mesoxalate (1) at 120 °C to form 2 (equation 2)2. Other cycloadditions of this ester with various dienes, which were carried out in a sealed tube at 130-135 °C, are shown in equations 3 and 43. It is noteworthy that no product was isolated from the action of diethyl mesoxalate on cyclopentadiene it was suggested3 that the cycloadduct reverted to its components at the high temperature required for the reaction. 

An extensive review of the hetero-Diels-Alder reactions of 1-oxabuta-1,3-dienes has been published. Ab initio calculations of the Diels-Alder reactions of prop-2-enethial with a number of dienophiles show that the transition states of all the reactions are similar and synchronous.Thio- and seleno-carbonyl compounds behave as superdienophiles in Diels-Alder reactions with cyclic and aryl-, methyl-, or methoxy-substituted open-chain buta-1,3-dienes.The intramolecular hetero-Diels-Alder reactions of 4-benzylidine-3-oxo[l,3]oxathiolan-5-ones (100) produce cycloadducts (101) and (102) in high yield and excellent endo/exo-selectivity (Scheme 39). A density functional theoretical study of the hetero-Diels-Alder reaction between butadiene and acrolein indicates that the endo s-cis is the most stable transition structure in both catalysed and uncatalysed reactions.The formation and use of amino acid-derived chiral acylnitroso hetero-Diels-Alder reactions in organic synthesis has been reviewed. The 4 + 2-cycloadditions of A-acylthioformamides as dienophiles have been reviewed. ... 

The reaction of diazoazoles and isocyanates leading to azolo-tetra-zinones of type 258 (Scheme 75) can be regarded as a [7 -l- 2]cycloaddition of the diazoazoles to the electron-deficient hetero double-bond of the isocyanates (pathway a) or, alternatively, as a two-step reaction involving [3 -I- 2]cycloaddition of the diazoazoles to the isocyanates, leading to the spirostructure 259 and subsequent [l,5]acyl shift (pathway b). An additional two-step mechanism (pathway c) could involve nucleophilic attack by the azole ring nitrogen on the carbonyl isocyanate to give a zwitterionic intermediate that collapses to the [7 + 2]cycloadduct 258. 

---