1,3-Butadiene, 2-methyl-4- Diels-Alder reactions

A second synthesis of cobyric acid (14) involves photochemical ring closure of an A—D secocorrinoid. Thus, the Diels-Alder reaction between butadiene and /n j -3-methyl-4-oxopentenoic acid was used as starting point for all four ring A—D synthons (15—18). These were combined in the order B + C — BC + D — BCD + A — ABCD. The resultant cadmium complex (19) was photocyclized in buffered acetic acid to give the metal-free corrinoid (20). A number of steps were involved in converting this material to cobyric acid (14). 

Most Diels-Alder reactions, particularly the thermal ones and those involving apolar dienes and dienophiles, are described by a concerted mechanism [17]. The reaction between 1,3-butadiene and ethene is a prototype of concerted synchronous reactions that have been investigated both experimentally and theoretically [18]. A concerted unsymmetrical transition state has been invoked to justify the stereochemistry of AICI3-catalyzed cycloadditions of alkylcyclohexenones with methyl-butadienes [12]. The high syn stereospecificity of the reaction, the low solvent effect on the reaction rate, and the large negative values of both activation entropy and activation volume comprise the chemical evidence usually given in favor of a pericyclic Diels-Alder reaction. 

Trifluoromethanesulfonic acid (triflic acid) in toluene greatly activates the Diels-Alder reaction of benzaldehydes with dimethylated 1,3-butadienes [89] (Table 4.22). With mono-methylated 1,3-butadienes the reaction gives less... 

A systematic study of the effect of pressure and density on the regiochemical course of the Diels-Alder reactions of methyl acrylate and 2-substituted 1,3-butadienes carried out in SC-CO2 was recently reported [87]. The reactions were compared with those carried out in a conventional medium such as toluene. Some results are illustrated in Table 6.15. 

Table 6.15 Regioselectivity of Diels-Alder reactions of methyl acrylate with 2-substituted-l,3-butadienes in sc- CO2 and PhMe...

Diels-Alder reactions provide one of the few general methods of forming two carbon-carbon bonds simultaneously. The main features of these reactions are described in Box 1.3. The reaction finds widespread industrial use for example hardeners for epoxy resins are made by reaction of maleic anhydride with dienes such as 2-methyl-1,4-butadiene. 

In 1995, these authors applied this methodology to the first total synthesis of the biosynthetically and unusual marine natural products, gracilins B and Thus, the key step of this synthesis was the enantioselective Diels-Alder reaction of 2-((trimethylsilyl)methyl)-butadiene with A-(2-iert-butylphenyl)maleimide in... 

Synthetic Applications of the Diels-Alder Reaction. Diels-Alder reactions have long played an important role in synthetic organic chemistry.74 The reaction of a substituted benzoquinone and 1,3-butadiene, for example, was the first step in one of the early syntheses of steroids. The angular methyl group was introduced by the methyl group on the quinone and the other functional groups were used for further elaboration. 

On the other hand, numerous examples are already known in which monomeric metaphosphoric esters are generated by thermolysis reactions. Most worthy of mention in this context is the gas phase pyrolysis of the cyclic phosphonate 150 which leads via a retro-Diels-Alder reaction to butadiene and monomeric methyl metaphosphate (151) 108,109, no). While most of the phosphorus appears as pyrophosphate and trimeric and polymeric metaphosphate, a low percentage (<5%) of products 152 and 153 is also found on condensation of the pyrolyzate in a cold trap containing diethylaniline or N,N,N, N,-tetraethyl-m-phenylene-diamine. The... 

Inukai and Kojima (9) have studied the aluminum chloride catalyzed diene condensation of butadiene and methyl acrylate in benzene solution. The stoichiometry for this Diels-Alder reaction is... 

Consider the Diels-Alder reaction between 1,3-butadiene (B) and methyl acrylate (M) discussed in Illustration 8.3. 

In Illustrations 8.3 and 8.6 we considered the reactor size requirements for the Diels-Alder reaction between 1,4-butadiene and methyl acrylate. For the conditions cited the reaction may be considered as a pseudo first-order reaction with 8a = 0. At a fraction conversion of 0.40 the required PFR volume was 33.5 m1 2 3, while the required CSTR volume was 43.7 m3. The ratio of these volumes is 1.30. From Figure 8.8 the ratio is seen to be identical with this value. Thus this figure or equation 8.3.14 can be used in solving a number of problems involving the... 

The first report suggesting specific activation of an organic reaction by MW was that of Berlan et al. [28] who observed that some Diels-Alder reactions occurred more rapidly on MW heating than under conventional heating at the same temperature (95 °C). The reactions were performed in two different solvents, xylene and dibutyl ether and the rate enhancements were slightly higher in xylene, the less polar solvent. For example the rate enhancement of the reaction of 2,3-dimethyl-l,3-butadiene 21 with methyl vinyl ketone 22 was 8 times in xylene and 2.3 times in dibutyl ether, based on the half lives of the reactions. Reaction of anthracene 3 with diethyl maleate 23 in xylene (Scheme 4.12) resulted in an approximately fourfold rate in-... 

Whilst it is obviously valuable to measure the solubility of reagents in the SCF, it is important to be aware that the solubility in a multicomponent system can be very different from that in the fluid alone. It is also important to note that the addition of reagents and catalysts can have a profound effect on the critical parameters of the mixture. Indeed, at high concentrations of reactants, the mole fraction of C02 is necessarily lower and it may not be possible to achieve a supercritical phase at the temperature of interest. Increases in pressure (i.e. further additions of C02) could yield a single liquid phase (which would have a much lower compressibility than scC02). For example, the Diels-Alder reaction (see Chapter 7) between 2-methyl-1,3-butadiene and maleic anydride has been carried out a pressure of 74.5 bar and a temperature of 50 °C, assuming that this would be under supercritical conditions as it would if it were pure C02. However, the critical parameters calculated for this system are a pressure of 77.4bar and a temperature of 123.2 °C, far in excess of those used [41]. 

Ohfune and coworkers78 used Diels-Alder reactions between 2-trimethylsilyloxy-l,3-butadiene (63) and acrylate esters 64 to synthesize constrained L-glutamates which they intended to use for the determination of the conformational requirements of glutamate receptors. The reactions between 63 and acrylate esters 64a and 64b did not proceed. Changing the ethyl and methyl ester moieties into more electron-deficient ester moieties, however, led to formation of Diels-Alder adducts, the yields being moderate to good. In nearly all cases, the cycloadducts were obtained as single diastereomers, which is indicative of a complete facial selectivity (equation 22, Table 1). Other dienes, e.g. cyclopentadiene and isoprene, also showed a markedly enhanced reactivity toward acrylate 64g in comparison with acrylate 64a. 

The behavior described above has been verified by experiment and calculation on numerous substituted dienes and dienophiles. For example Fig. 10.13 shows results for 2°-D isotope effects on Diels-Alder reactions of 2-methyl-butadiene with cyano-ethylene and 1,1-dicyano-ethylene. The calculated and experimental isotope effects are in quantitative agreement with each other and with the results on (butadiene + ethylene). In each case the excellent agreement between calculated and observed isotope effects validates the concerted mechanism and establishes the structure of the transition state as that shown at the bottom center of Fig. 10.11 and the left side of Fig. 10.12a. 

In practice, the synthesis was carried out as outlined in the retrosynthetic Scheme 13.2.8. The Diels-Alder reaction between butadiene and (+)-(/ )-5-methyl-2-cyclohexenone (31), in the presence of SnCl in anhydrous acetonitrile solution at... 

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. ... 

Density functional theory has been used to investigate the Diels-Alder reactions of triazolinedione with s-cis- and. y-fran -butadiene. " Combined quantum mechanics-molecular mechanics calculations have been used to investigate the asymmetric Diels-Alder reaction of cyclopentadiene with the complex dienophiles AICI3-methyl acrylate and methoxyaluminium dichloride-acrolein.Equilibrium constants have been determined for the molecular complexes formed from 1-alkyl-1-(2-naphthyl)ethenes and 1-vinylnaphthalene with TCNE in C1(CH2)2C1 at 27.1 °C ... 

A catalytic asymmetric Diels-Alder reaction was developed by using 3-(3-borylpropenoyl)oxazolidin-2-ones 146. In the reactions of butadiene, isoprene, or 2-methyl-l,3-pentadiene and 146, in the presence of a chiral titanium catalyst 147, the cyclohexene derivatives 148 were formed. 

Theoretical calculations (6-31G ) have been used to compare the energies of four possible transition states for Diels-Alder reaction of the BF3 complex of methyl acrylate with 1,3-butadiene. The results are summarized in Fig. 6.4. The endo transition state with the s-trans conformation of the dienophile is preferred to the others by about 2kcal/mol.14... 

Butadienes substituted with alkoxy groups in the 2-position, e.g., 2-ethoxy-1,3-butadiene,6 have been prepared from methyl vinyl ketone, but they required several conversions and a tedious spinning-band distillation to purify the product. This slight modification of the House procedure has been used to conveniently prepare 2-trimethylsilyloxy-l,3-butadiene from the readily available methyl vinyl ketone. This one-step procedure has provided large amounts of a new and reactive diene for Diels-Alder reactions, as illustrated in Table I. 

In the area of reaction energetics. Baker, Muir, and Andzehn have compared six levels of theory for the enthalpies of forward activation and reaction for 12 organic reactions the unimolecular rearrangements vinyl alcohol -> acetaldehyde, cyclobutene -> s-trans butadiene, s-cis butadiene s-trans butadiene, and cyclopropyl radical allyl radical the unimolecular decompositions tetrazine -> 2HCN -F N2 and trifluoromethanol -> carbonyl difluoride -F HF the bimolecular condensation reactions butadiene -F ethylene -> cyclohexene (the Diels-Alder reaction), methyl radical -F ethylene -> propyl radical, and methyl radical -F formaldehyde -> ethoxyl radical and the bimolecular exchange reactions FO -F H2 FOH -F H, HO -F H2 H2O -F H, and H -F acetylene H2 -F HC2. Their results are summarized in Table 8.3 (Reaction Set 1). One feature noted by these authors is... 

When 3,4-dihydro-2//-pyran (555) is given pulses of a laser beam, it decomposes by a retro-Diels-Alder reaction into acrolein and ethylene (78JA6111). 4-Methyl-5,6-dihydro-2//-pyran (555a) when irradiated in methanol through which oxygen is passed gives a mixture of four cyclic products on treatment with sodium borohydride (79JCS(P1)1806). Pyrolysis of the dihydropyran (555) at 350 °C yields butadiene. 

Diels-Alder reactions of bis(trimethylsilyl)acetylene.1 A catalyst obtained from TiCl4 and (C2H5)2A1C1 (1 20) effects Diels-Alder reactions of this acetylene with butadiene and methyl-substituted derivatives to form l,2-bis(trimethylsilyl)-cyclohexa- 1,4-dienes in 70-78% yield (equation I). The yield is low (15%) only when R, R4 = CH3,R2,R3 = H because of polymerization of the diene. The products undergo thermal dehydrogenation at 240° to form l,2-bis(trimethylsilyl)ben-zenes in almost quantitative yield. This cycloaddition has been effected in low yield with an iron-based catalyst. 

BUTADIENE. [CAS 106-90-0]. CHrCH C CH3, 1,3-butadiene (methyl-allene), formula weight 54.09. bp —4.41cC, sp gr 0.6272, insoluble in H2 O. soluble in alcohol and edier in all proportions, Butadiene is a very reactive compound, arising from its conjugated double-bond structure. Most butadiene production goes into die manufacture of polymers, notably SBR (styrene-butadiene rubber) and ABS (acryloiiitrile-buladiene-slyrene) plastics. Several organic syntheses, such as Diels-Alder reaction, commence with the double-bond system provided by this compound. 

Chiral (.S, .S )-diazaaluminolidine catalyst brought about the first highly enantioselective catalytic Diels-Alder reaction of an achiral C2v-symmetric dienophile with an achiral diene. Addition of 2-methoxybutadiene to A-o-tolylmaleimide in the presence of 20 mol % (5,5)-diazaaluminolidine gave rise to the cycloadduct in 98% yield and 93% ee one recrystallization from i-PrOH-hexane furnished the enantiomerically pure compound [57] (Eq. 8A.34). The Diels-Alder reaction of 2-((trimethylsilyl)methyl)butadiene and A-aryimaleimide promoted by this catalyst has been successfully applied to the enantioselective total synthesis of Gracilins B and C [58],... 

Dichlorobis(diisopropoxy)titanium(IV). Titanium(IV) chloride. Zinc iodide. DIELS-ALDER REACTIONS 2-Acetoxy-I-methoxy-3-trimethylsilyloxy-1,3-butadiene. 4-Acetoxy-1 -trimethylsilyl-1,3-butadiene. Benzyl irans-l,3-butadiene-l-carbamate. 1,3-Bis(/-butyldimethylsilyloxy)-2-aza-1,3-diene. 2,3-Bis(trimethylsilyl)methyl-1.3-buladiene (10-1,3-Dimethoxybutadiene 4-I)iniethyhnnino 1,1,2... 

Solid-phase three-component domino-Knoevenagel-hetero-Diels-Alder reaction can also be performed using a resin-linked 1,3-dicarbonyl compound such as 100 with aldehydes and an enol ether to give dihydropyrans 102 via the intermediately formed 1-oxa-l,3-butadiene 101 (Scheme 5.18) [30], The resin can be deaved off after the reaction by solvolysis, for instance using sodium methanolate to give the corresponding methyl ester 103 as a mixture of diastereomers. The overall yield varies from 12 to 37% and the selectivity from 1 1 to 1 5 in favor of the tis-product depending on the applied aldehyde. The crude dihydropyrans thus obtained are reasonably pure (> 90% HPLC). 

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