Cyclohexadienes, synthesis

Although cobaltacyclopentene complexes react preferentially with alkenes, they can be preformed and reacted with alkynes, providing an alternative stoichiometric permutation for 1,3-cyclohexadiene synthesis (Scheme 22). ... 

Birkinshaw, T. N., Tabor, A. B., Holmes, A. B., Kaye, P., Mayne, P. M., Raithby, P. R. The products of an imino Diels-Alder reaction with 2-(trimethylsiloxy)cyclohexadiene synthesis, x-ray crystal structures, and mechanistic implications. J. Chem. Soc., Chem. Common. 1988, 1599-1601. 

These findings of breaking aromaticity provide a completely new pathway for cyclohexadiene synthesis. The intermediary aromatic carbonyl/ATPH complex based on X-ray crystallographic structures is shown in Fig. 1, displaying the complete stereo-blocking of carbonyl oxygen from the normal carbonyl attack of nucleophiles (Scheme 4). 

Several substituted cyclohexane derivatives may also be obtained by the reduction of a benzenoid precursor. Partial reduction of resorcinol, for example, and subsequent methyla-tion yields 2-methylcyclohexane-I,3-dione, which is frequently used in steroid synthesis (M.S. Newman, 1960 see also p. 71f.), From lithium-ammonia reduction of alkoxybenzenes l-alkoxy-l,4-cyclohexadienes are obtained (E.J. Corey, 1968 D). 

Diacetoxylation of various conjugated dienes including cyclic dienes has been extensively studied. 1,3-Cyclohexadiene was converted into a mixture of isomeric l,4-diacetoxy-2-cyclohexenes of unknown stereochemistry[303]. The stereoselective Pd-catalyzed 1,4-diacetoxylation of dienes is carried out in AcOH in the presence of LiOAc and /or LiCI and beiizoquinone[304.305]. In the presence of acetate ion and in the absence of chloride ion, /rau.v-diacetox-ylation occurs, whereas addition of a catalytic amount of LiCl changes the stereochemistry to cis addition. The coordination of a chloride ion to Pd makes the cis migration of the acetate from Pd impossible. From 1,3-cyclohexadiene, trans- and ci j-l,4-diacetoxy-2-cyclohexenes (346 and 347) can be prepared stereoselectively. For the 6-substituted 1,3-cycloheptadiene 348, a high diaster-eoselectivity is observed. The stereoselective cij-diacetoxylation of 5-carbo-methoxy-1,3-cyclohexadiene (349) has been applied to the synthesis of dl-shikimic acid (350). 

The wM-diacetate 363 can be transformed into either enantiomer of the 4-substituted 2-cyclohexen-l-ol 364 via the enzymatic hydrolysis. By changing the relative reactivity of the allylic leaving groups (acetate and the more reactive carbonate), either enantiomer of 4-substituted cyclohexenyl acetate is accessible by choice. Then the enantioselective synthesis of (7 )- and (S)-5-substituted 1,3-cyclohexadienes 365 and 367 can be achieved. The Pd(II)-cat-alyzed acetoxylactonization of the diene acids affords the lactones 366 and 368 of different stereochemistry[310]. The tropane alkaloid skeletons 370 and 371 have been constructed based on this chemoselective Pd-catalyzed reactions of 6-benzyloxy-l,3-cycloheptadiene (369)[311]. 

Synthesis by oxidation remains the first choice for commercial and laboratory preparation of quinones the starting material (1) provided the generic name quinone. This simple, descriptive nomenclature has been abandoned by Chemicaly hstracts, but remains widely used (2). The systematic name for (2) is 2,5-cyclohexadiene-l,4-dione. Several examples of quinone synonyms are given in Table 1. Common names are used in this article. 1,2-Benzoquinone (3,5-cydohexadiene-l,2-dione) (3) is also prepared by oxidation, often with freshly prepared silver oxide (3). Compounds related to (3) must be prepared using mild conditions because of their great sensitivity to both electrophiles and nucleophiles (4,5). 

The synthesis of natural products containing the quinonoid stmcture has led to intensive and extensive study of the classic diene synthesis (77). The Diels-Alder cycloaddition of quinonoid dienophiles has been reported for a wide range of dienes (78—80). Reaction of (2) with cyclopentadiene yields (79) [1200-89-1] and (80) [5439-22-5]. The analogous 1,3-cyclohexadiene adducts have been the subject of C-nmr and x-ray studies, which indicate the endo—anti—endo stereostmcture (81). 

The application of this strategy to the synthesis of chiral cyclohexadienes has been demonstrated by Kiindig. Addition of MeLi to the Cr(CO)3-complexed chiral phenyl oxazoline 43 followed by reaction with allyl bromide produced cyclohexadiene 44 in 69% yield and >98% de. ... 

A useful and possibly more general alternative to the Lwowski synthesis- of 1,3-diphenylisoindoles involves condensation of a l,2-dibenzoyl-l,4-cyclohexadiene (e.g., 55) with ammonia or a primary amine. Cyclohexadiene derivatives of this type are easily prepared by Riels-Alder addition of a 1,3-diene to dibenzoylacetylene, and these adducts lead directly, and in high yield, to the corresponding isoindoles (56). The reaction is closely related to the well-known synthesis of pyrroles by condensation of 1,4-diketones with ammonia. 4,7-Dihydro- and 4,5,6,7-tetrahydroisoindoles (57 and 58) have been... 

Cyclohexadiene-d.s -diols as versatile intermediates in the synthesis of natural heterocycles 96CC1993. 

Cycloheptatrienes, synthesis of 801 Cyclohexadienes 800, 801 Cyclohexanols, synthesis of 838 Cyclopentanones, naturally occurring 321 Cyclopentanone sulphoxides, reactions of 341... 

Diels-Alder reactions of 1,3-cyclohexadienes and 3-(trimethylsilyl)propynoates. A new synthesis of orf/7o-(trimethylsilyl)benzoate esters [149]... 

The synthesis and Diels-Alder reactions of enantiopure (-)-tra s-benzo[d]thiin-S,S -dioxide 7 were described. Whereas with cyclopentadiene and 1,3-cyclohexadiene a high endolexo ratio (> 99/1) was obtained, with fiiran these values are lower depending on the reaction conditions... 

Regioselective Beckmann rearrangements were used as key steps in the synthesis of phosphonoalkyl azepinones (Scheme 36) [43b] and in a formal total synthesis of the protein kinase C inhibitor balanol (Scheme 37) the optically active azide 197 derived from cyclohexadiene mono-oxide was converted into ketone 198 in several steps. After preparation of the oxime tosylates 199 (2.3 1 mixture), a Lewis acid mediated regioselective Beckmann rearrangement gave the lactams 200 and 201 in 66% and 9% yield, respectively. Lactam 201 underwent a 3-e im-ination to give additional 200, which served as a key intermediate in a balanol precursor synthesis (Scheme 37) [43 cj. 

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). 

A general method for the synthesis of highly substituted styrenes as 6/4-91, vinyl-cyclohexadienes and related compounds was developed by Xi, Takahashi and coworkers [301] by reacting an intermediately formed five-membered zirconacycle 6/4-89 with propargyl derivatives 6/4-90 or allyl bishalides in the presence of CuCl (Scheme 6/4.21). 

---