Carbocyclizations thermal reaction

This system covers concerted reactions of the n electron systems on two reactants to form new a bonds yielding carbocyclic rings with a single unsaturation. If the reaction follows the rule of maximum orbital overlap, then it is a suprafacial, suprafacial process and is termed a [,r4 + r t] reaction. By the Woodward-Hoffmann rules this is a symmetry-allowed thermal reaction [13]. 

Intermolecular Allylboration. A tandem aza[4+2] cycloaddition/allyl-boration three-component reaction has been designed based on the prece-dented carbocyclic [4- -2] cycloaddition/allylboration and a snbsequent one-pot variant. Thns, the thermal reaction between hydrazonobutadienes 138, A-substitnted maleimides, and aldehydes provides polysnbstituted a-hydroxy-alkylpiperidines 141 via the cyclic allylboronate intermediate 139 and the proposed chairlike transition stmctnre 140 (Eq. 103). Monoactivated dienophiles like acrylates fail to react with heterodienes 138 bnt the scope of aldehydes is very broad both ahphatic and aromatic aldehydes are snitable, inclnding electron-rich ones. An inverse electron-demand variant to access the corresponding dihy-dropyran derivatives via the intermediacy of enantiomerically enriched pyranyl allylic boronate 76 has been snbsequently developed (see Eq. 64). ° ... 

A rich cycloaddition chemistry with phosphaalkynes 9 may be expected from cross-conjugated carbocyclic compounds of the heptafulvene type (in the present case, tropone (41)). Thermal [rtf - and [jt a ]-cycloadditions are allowed by symmetry. Thus, the thermal reaction of tropone (41) with an excess of the phosphaalkynes 9 a, 9 e (without a solvent) furnishes the diphosphatetracyclic products 43a,b [45]. The initiating Diels-Alder reaction to 42 (there are P-NMR spectroscopic indications for its intermediate formation) is accordingly followed by a [2 -t- 2 + 2]-cycloaddition (ashomo-Diels-Alder reaction) with a second equivalent of the phosphaalkyne to yield 43 (Scheme 6-9). The observed peri- and regioselectivities of the two reaction steps can be confirmed by frontier orbital calculations [43],... 

Differential scanning calorimetry (DSC) experiments on the various dimeric carbocycles indicated that, depending on the length of the alkyl groups, thermal polymerization had occurred between 100 and 125°C as an abrupt, exothermic process. The narrow temperature range for each exotherm was suggestive of a chain reaction however, IR spectroscopy revealed the absence of acetylene functionalities in the polymerized material. Consequently, none of the substi-... 

The tandem-Knoevenagel-ene reaction is a powerful tool to synthesize five-and six-membered carbocycles.2 5 The process is exemplified by the diastereoselective synthesis of 4a. Compound 4a has been obtained In both enantiomeric forms and as a racemate according to the procedure described here. The sequence includes the Knoevenagel reaction of citronellal, 1, and dimethyl malonate, 2, followed by the intramolecular ene cyclization of the chiral 1,7-diene 3 to yield the trans 1,2-disubstituted products 4a and 4b. Whereas the thermal cyclization of 3 at 160°C provides 4a and 4 b in a ratio of only 89.7 10.3, the Lewis acid... 

This chapter deals with thermal ring-closure reactions of dienes and polyenes resulting in carbocyclic compounds the formation of heterocycles is mentioned only occasionally. The account is highly selective, concentrating on recent work, since two comprehensive general reviews have appeared1,2. Other pertinent reviews are cited at appropriate places in the text. 

The Alder-ene reaction has traditionally been performed under thermal conditions—generally at temperatures in excess of 200 °C. Transition metal catalysis not only maintains the attractive atom-economical feature of the Alder-ene reaction, but also allows for regiocontrol and, in many cases, stereoselectivity. A multitude of transition metal complexes has shown the ability to catalyze the intramolecular Alder-ene reaction. Each possesses a unique reactivity that is reflected in the diversity of carbocyclic and heterocyclic products accessible via the transition metal-catalyzed intramolecular Alder-ene reaction. Presumably for these reasons, investigation of the thermal Alder-ene reaction seems to have stopped almost completely. For example, more than 40 papers pertaining to the transition metal-catalyzed intramolecular Alder-ene reaction have been published over the last decade. In the process of writing this review, we encountered only three recent examples of the thermal intramolecular Alder-ene reaction, two of which were applications to the synthesis of biologically relevant compounds (see Section 10.12.6). 

Functionalized cyclopropenes are viable synthetic intermediates whose applications [99.100] extend to a wide variety of carbocyclic and heterocyclic systems. However, advances in the synthesis of cyclopropenes, particularly through Rh(II) carboxylate—catalyzed decomposition of diazo esters in the presence of alkynes [100-102], has made available an array of stable 3-cyclopropenecarboxylate esters. Previously, copper catalysts provided low to moderate yields of cyclopropenes in reactions of diazo esters with disubstituted acetylenes [103], but the higher temperatures required for these carbenoid reactions often led to thermal or catalytic ring opening and products derived from vinylcarbene intermediates (104-107). 

The work reported by Eaton and coworkers can be summarized as reactions where an allene system in conjugation with a further unsaturated functionality reacts with carbon monoxide in the presence of an iron-carbonyl complex such as Fe(CO)5 under photochemical and thermal conditions when Fe2(CO)9 is used. When diallenes are used (X=R2C=C, Scheme 9.24), five-membered carbocyclic products are obtained [51, 52], whereas when allenyl ketones (X = O) are applied, five-membered lactones are generated [53, 54]. The use of allenylimines (X = NR) leads to five-membered lactams under these conditions [55]. 

Although a number of multistep procedures are available for the introduction of five-membered carbocycles, their direct formation in a thermal cycloaddition is rare.6 Interest in the potential application of such a three-carbon + two-carbon cyclopentane cycloaddition has been derived from the expectation that such a process could prove to be an effective complement to the four-carbon + two-carbon Diels-Alder reaction which is used extensively in the regio- and stereocontrol led preparation of functionalized six-membered carbocycles. 

Figure 4.11). This reaction, a Claisen rearrangement, transfers the PEP-derived side-chain so that it becomes directly bonded to the carbocycle, and so builds up the basic carbon skeleton of phenylalanine and tyrosine. The reaction is catalysed in nature by the enzyme chorismate mutase, and, although it can also occur thermally, the rate increases some 106-fold in the presence of the enzyme. The enzyme achieves this by binding the pseudoaxial conformer of chorismic acid, allowing a transition state with chairlike geometry to develop. 

Horton et al. were interested in the synthesis of tetra-C-substituted carbocycles, and extensively studied asymmetric Diels-Alder reactions employing acyclic unsaturated carbohydrate derivatives. Thus, the thermal cycloaddition of the D-arabinose-derived c/i-dienophile (Z)-100 with cyclopentadiene gave endo-adduct 101 in excellent optical purity. The high diastereo-facial differentiation in this reaction arises from a highly favored conformation at the allylic center [76,77] (Scheme 10.33). Therefore, conformer 102 seems to be more favored than 103, where the latter suffers from severe allylic strain between the methoxycarbonyl and the C4-acetoxy group... 

Keck and co-workers have investigated the exo cyclizations of the allylstan-nanes (Z)-158 and ( )-159 these reactions can be promoted by both thermal and Lewis acidic conditions (Table 11-10) [54]. As illustrated in Table 11-10, the (Z)-stannane 158 preferentially forms the 1,2-syn adduct 160 under both thermal promotion and catalysis by Bp3 OEt2. In contrast, the (i )-stannane 159 cyclizes to form the, 2-anti carbocycle 161 as the major adduct in the BF -OEta-catalyzed allylation, while the, 2-syn carbocycle 160 is the major adduct in the thennji] allylation process. 

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