1.3- Cyclohexadiene imines

In contrast, intramolecular cycloaddition of the dienylketenimines 136 (R = Me, OMe, OCOMe R = Me, i-Pr), generated in situ, gives rise to the formation of the cyclohexadiene imines 137. ... 

The use of chiral bis(oxazoline) copper catalysts has also been often reported as an efficient and economic way to perform asymmetric hetero-Diels-Alder reactions of carbonyl compounds and imines with conjugated dienes [81], with the main focus on the application of this methodology towards the preparation of biologically valuable synthons [82]. Only some representative examples are listed below. For example, the copper complex 54 (Scheme 26) has been successfully involved in the catalytic hetero Diels-Alder reaction of a substituted cyclohexadiene with ethyl glyoxylate [83], a key step in the total synthesis of (i )-dihydroactinidiolide (Scheme 30). 

The processes of oxidation of cyclohexadiene, 1,2-substituted ethenes, and aliphatic amines are decelerated by quinones, hydroquinones, and quinone imines by a similar mechanism. The values of stoichiometric inhibition coefficients / and the rate constants k for the corresponding reactions involving peroxyl radicals (H02 and >C(0H)00 ) are presented in Table 16.3. The/coefficients in these reactions are relatively high, varying from 8 to 70. Evidently, the irreversible consumption of quinone in these systems is due to the addition of peroxyl radicals to the double bond of quinone and alkyl radicals to the carbonyl group of quinone. 

Titanium silicate molecular sieves not only catalyze the oxidation of C=C double bonds but can be successfully employed for the oxidative cleavage of carbon-nitrogen double bonds as well. Tosylhydrazones and imines are oxidized to their corresponding carbonyl compounds (243) (Scheme 19). Similarly, oximes can be cleaved to their corresponding carbonyl compounds (165). The conversion of cyclic dienes into hydroxyl ketones or lactones is a novel reaction reported by Kumar et al. (165) (Scheme 20). Thus, when cyclopentadienes, 1,3-cyclohexadiene, or furan is treated with aqueous H202 in acetone at reflux temperatures for 6 h in the presence of TS-1, the corresponding hydroxyl ketone or lactone is obtained in moderate to good yields (208). 

The cycloaddition of dienes to imines to form tetrahydropyridines (equation 46) has been investigated extensively40. Ordinary imines are not sufficiently reactive to add to dienes they have to be activated by the presence of electron-withdrawing substituents. Thus the triester 70 adds to cyclopentadiene under atmospheric pressure to form 71 (equation 47). The reactions with other dienes (cyclohexadiene, isoprene or 2,3-dimethylbuta-l,3-diene) require high pressures41. 

Cyclohexadiene 45 was converted to 46 by what has proven to be a general method for preparation of the cyclohexa-2,4-dien-l-one ring system.2 Fragmentation of the aziridinyl imine in 46 at 110 °C gave an intermediate diazoalkane which underwent an intramolecular 1,3-dipolar cycloaddition to give the pyrazoline 47. At 140 °C, pyrazoline 47 expelled N2 and rearranged to the tricyclic ketone 48. The development of this and related bicyclizations29 illustrated a practical synthetic equivalence of an intramolecular diene-carbene 4-1-1 cycloaddition in the cyclohexa-2,4-dien-l-one series. 

Over the past 15 years, we developed three procedures for the iron-mediated carbazole synthesis, which differ in the mode of oxidative cyclization arylamine cyclization, quinone imine cyclization, and oxidative cyclization by air (8,10,557,558). The one-pot transformation of the arylamine-substituted tricarbonyl(ri -cyclohexadiene) iron complexes 571 to the 9H-carbazoles 573 proceeds via a sequence of cyclization, aromatization, and demetalation. This iron-mediated arylamine cyclization has been widely applied to the total synthesis of a broad range of 1-oxygenated, 3-oxygenated, and 3,4-dioxygenated carbazole alkaloids (Scheme 5.24). 

In the quinone imine cyclization of iron complexes to carbazoles, the arylamine-substituted tricarbonyl(ri -cyclohexadiene)iron complexes 571 are chemoselectively oxidized to a quinone imine 574 prior to cyclodehydrogenation. This mode of cyclization is particularly applicable for the total synthesis of 3-oxygenated tricyclic carbazole alkaloids (Scheme 5.25). 

These addition reactions require formation of an imino-cyclohexadiene intermediate (Fig. 13.41). In cases where the ipso substituent is a proton, tautomeriza-tion to form the substituted aniline derivative is fast, and such intermediates have not been isolated. On the other hand, in situations where the nucleophile adds to a substituted ring position, the intermediate can undergo further secondary reactions. For example Novak et al. showed that the 4-biphenylylnitrenium ion reacts with water forming the imine cyclohexadiene intermediate 74, which in turn experiences an acid-catalyzed phenyl shift reaction to 76 via 75 (Fig. 13.42). 

Cyclohexadiene-l,4-dione, see 1,4-Benzoquinone, 2207 2,5-Cyclohexadienone-4-imine, see 1,4-Benzoquinone monoimine, 2253 f Cyclohexane, 2451... 

Asymmetric addition of PhLi, coordinated by the chiral ligand 200, to the prochiral imine complex 199 generates 201. Discrimination between enantiotopic sites at C(2) and C(6) occurs. Then the 5,6-mmv-disubstituted 1,3-cyclohexadienal 202 was prepared with 93% ee by electrophilic attack of propargyl bromide [50],... 

Some results described by Holmes and coworkers are consistent with the stereochemical outcome of equation (3). Cycloaddition of imine (10) with 2-trimethylsiloxy-l,3-cyclohexadiene afforded a mixture of adducts (11) and (12) with the exo isomer predominating (equation 4). In this example, only a single regioisomer was detected. 

Acyclic C-acyl imines have recently been studied as dienophiles.32-34 p j example, Prato and coworkers examined the reaction of imines (41) (equation 13) with several cyclic and acyclic 1,3-dienes. Under neutral conditions, (41) is unreactive as a dienophile. However, under Lewis acid catalysis these imines react to afford mixtures of adducts. With 1,3-cyclohexadiene, bicyclic adducts (42) and (43) are produced along with (44) in which the imine has acted as an azadiene. The ratios of these sorts of products are dependent upon the particular imine and diene used. The formation of adducts of type (43) proved to be both regio- and stereo-selective. Product formation in these cases can be rationalized lx>th by concerted and by stepwise ionic mechanisms. ... 

This concept was extended to imines derived from a-amino acids. Several imines 8 react with cyclopentadiene (4) and 1,3-cyclohexadiene (9) yielding adducts 10 and 11 with good to excellent diastereoselectivity, while addition to acyclic dienes 12 proceeds with moderate selectivity68. 

These imines also reacted cleanly with cyclic dienes such eis cyclopenta-diene and 1,3-cyclohexadiene, but in these cases product stereochemistry was not elucidated. 

The complex incorporating the chiral d-vahnol derived imine auxiliary has been used in the synthesis of (+)-acetoxytubipofuran. This auxiliary delivered the dearomatized tetrasubstituted cyclohexadiene intermediate as a single enantiomer (Scheme 23) [50]. 

The chromium complex 46 of benzaldehyde imine is also a good substrate for asymmetric conjugate addition of organolithium reagents, where the reaction was mediated by a stoichiometric amount of chiral diether 18 in toluene to give, following propargylic electrophile incorporation, the cyclohexadienal 48 in up to 93% ee (Scheme 13) [38]. SAMP [(S)-l-amino-2-(methoxymethyl)pyrrolid-ine] hydrazones were used effectively in diastereoselective nucleophilic additions to (arene)Cr(CO)3 complexes [39]. 

A hetero-Diels-Alder reaction between the imine (115) and the cyclohexadiene (116) produces the aza-bicyclo-octane (117), which after Baeyer-Villiger ring expansion followed by reduction, gave the triol (1l8), an advanced intermediate with all three chiral centres in their correct relative stereochemistry, for the synthe-... 

The 4-I-2-cycloaddition of trimethylsilyl (TMS)-substituted cyclopentadiene with phosphorylated nitroso alkenes formed bicyclo 1,2-oxazines. However, as dienophiles, phosphorylated nitroso alkenes also react with cyclopentadiene and cyclohexadiene. The phosphoramidite-rhodium complex (84)-catalysed 4- -2-cycloaddition of a,fi-unsaturated imines with isocyanates produced pyrimidinones in good yields and with high enantioselectivities. ... 

BicycUc N-allyl anilines 40, and armulated quinoHnes 41, could be prepared by means of hetero Diels-Alder cycloadditions of cyclopentadiene 39 (n= 1) and cyclohexadiene 39 (n= 2), respectively, and imine 38 [9ej. The reaction of cyclopentadiene 39 (reaction as dienophile) in the presence of strong Lewis acids such as BE3 and SOj directly resulted the formation of the quinoline derivative 41 (n=l, P benzoyl) with 87-88% even at ambient temperature. The use of weaker Lewis acids (CuCl) and low temperatures (-20 °C) enabled to isolate some unstable bicycle 40 (8%, R= NO2), which could be completely converted into the quinoline 41 upon heating or after treatment with a stronger Lewis acid. In the case of the conversion of cyclohexadiene 39 (n=2), the acceptor substituted anilines 38 (R = NOj, Cl) predominantly reacted as dienophiles to give the bicycles 40 with... 

Kobayashi M, Uneyama K, Hamada N, Kashino S (1995) N -(4-oxo-2,5-cyclohexadien-l-ylidene)-N -substituted-2,2,2-trifluoroethanimidamides (p-benzoquinone imine derivatives) syntheses of trifluoromethylated 6-hydroxybenzimidazoles and spiro dienone diazacarbocy-cles. J Org Chem 60 6402-6407... 

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