1,3-Butadiene

[106-99-0]  · C4H6  · 1,3-Butadiene  · (MW 54.09)

(co-monomer in synthetic elastomers and polymers, polybutadiene rubber, chloroprene, and nylon intermediate;1 4p partner in Diels-Alder reactions2)

Alternate Names: butadiene; a,g-butadiene; bivinyl; divinyl; vinylethylene; biethylene.

Physical Data: bp -4.5 °C/760 mmHg; mp -109 °C; fp <-7 °C; ρ-64 0.650.

Solubility: sol common organic solvents.

Form Supplied in: widely available in compressed liquid phase. Supplied in several grades ranging from 99.0-99.8% purity. Sizes available range incrementally from lecture bottles (100 g) to large gas cylinders (61 kg).

Preparative Methods: butadiene sulfone (2,5-dihydrothiophene 1,1-dioxide), a crystalline, nonhygroscopic, commercially available solid, can be used to generate 1,3-butadiene in situ: heating the sulfone at 100-130 °C induces loss of SO2.3b,3c

Handling, Storage, and Precautions: extremely flammable liquid and gas. Avoid polymerization initiators. Relatively nontoxic. Suspected chronic carcinogen. Acutely irritating to respiratory tract. 1,3-Butadiene (1) is used in the laboratory by condensing the gas directly into a reaction vessel, or by forming a saturated solution of the gas in the reaction solvent. For reactions run below rt (e.g. Lewis acid-catalyzed reactions), normal reaction flasks can be used. For higher temperature reactions, sealed tubes are required to prevent escape of (1). A particularly convenient, reusable apparatus is available from Ace Glass, Inc., and consists of a heavy-walled glass tube sealed on one end and threaded on the other. The threaded end can be sealed with a heavy Teflon plug fitted with an O-ring.

Reactivity.

1,3-Butadiene (1) participates as the 4p partner in [p4s + p22] cycloaddition reactions with a variety of dienophiles. The majority of these cycloadditions are normal Diels-Alder reactions (HOMOdiene-LUMOdienophile controlled).2,3a Theoretical predictions on the mechanism of Diels-Alder reactions of butadiene have pointed towards a synchronous concerted mechanism.4 1,3-Butadiene (1) is typically less reactive than substituted butadienes, except when steric factors prevent the diene from attaining the reactive s-cis conformation. For example Tetracyanoethylene reacts more slowly with (1) than with (E)-1-methyl-1,3-butadiene (103×), 2-phenyl-1,3-butadiene (191×), or (E)-1-methoxy-1,3-butadiene (50 934×).

Lewis Acid-Catalyzed Cycloadditions.

Friedel-Crafts type catalysts are reported to facilitate the cycloaddition reactions of (1) with a,b-unsaturated carbonyl compounds.5 With methyl vinyl ketone (eq 1), cycloaddition was effected in the presence of less than 1 molar equivalent of Aluminum Chloride, Tin(IV) Chloride, Boron Trifluoride, Iron(III) Chloride, or Titanium(IV) Chloride for 1 h at 25 °C. For comparison, the uncatalyzed reaction required 8-10 h at 140 °C in a sealed tube (75%). Acrolein, Methyl Vinyl Ketone, and Acrylic Acid all underwent effective catalyzed Diels-Alder reactions with (1) in good yields. The principal limitation of this reaction is polymerization of the 1,3-diene. For example, 2,3-dimethylbutadiene and cyclopentadiene underwent polymerization and dimerization, respectively, under these conditions.

In the cycloaddition of (1) with 2,5-cyclohexadienones in an approach to cis-clerodanes, the facial selectivity depended on the length of the carboxylate side-chain (eq 2).6 When the carboxylate was a significant distance from the ring (n = 2), cycloaddition occurred syn to the less bulky methyl group to afford the anti cycloadduct. Facial selectivity eroded with n = 1, and was reversed when the carboxylate was directly attached to the ring, to afford exclusively the syn diastereomer.

Lewis acids have also been used to catalyze the cycloaddition of (1) with alkynes (eq 3).7 A mixture of TiCl4 and Diethylaluminum Chloride promoted the [4 + 2] cycloaddition of phenyl(trimethylsilyl)acetylene and (1) to afford the dihydrobenzene adduct in 84% yield, which could be aromatized thermally to afford the ortho-disubstituted benzene in 92% yield. Cycloaddition of cycloalkenones with butadiene in the presence of AlCl3 affords the expected cis-fused systems for n = 2, 3, 4 (eq 4).8 Partial or total isomerization of the cis adduct to the more stable trans isomer was observed with R = H.

A highly regioselective and moderately stereoselective cycloaddition of (1) with the g,d-double bond of a dienone was effected by AlCl3 catalysis in 37% yield (eq 5).9 The cycloadduct formally arising from approach of butadiene syn to the enone ring predominated initially, and was shown to isomerize to the more stable anti product under the reaction conditions. Contrasteric facial selectivity was observed in the Lewis acid-catalyzed cycloaddition of (1) with g-alkoxycycloalkenones (eq 6).10 When n = 1, cycloaddition at rt in the presence of catalytic AlCl3 afforded predominately the syn cycloadduct (76%; 13:1 syn/anti). Under similar reaction conditions with n = 2, the syn cycloadduct was also the major product (10:1 syn/anti). The divergence of these results with those obtained with g-alkylcycloalkenones was discussed, and a tentative theoretical model was proposed to account for the syn selectivity.

Montmorillonite K10 exchanged with FeIII has been reported to catalyze the Diels-Alder reaction of butadiene with acrolein (eq 7).11 Cycloaddition occurs at rt in high yield in the presence of 1.8 g catalyst per 15 mmol cycloaddition partners. Other dienes reacted with equal facility with acrolein under these conditions.

Asymmetric Diels-Alder Reactions.

Cycloaddition of (1) with a methacrylate dienophile using a camphor lactam imide in the presence of Lewis acid affords the cyclohexenecarboxylate cycloadduct in 61% yield with 85:15 p-facial selectivity.12 Presumably the steric bulky of the coordinated metal forces the methacrylate to adopt an s-trans conformation as shown (eq 8), and cycloaddition occurs from the less crowded bottom face of the complex. A pyrrolidin-2-one auxiliary containing the bulky 5-(trityloxymethyl) group was effective at asymmetric induction in the Lewis acid-catalyzed cycloaddition of (1) with a fumarate dienophile (eq 9).13 The cyclohexenedicarboxylate was obtained in 52% yield and 96% de. Other dienophiles and Lewis acids were examined and found to be equally effective, giving high endo selectivity (&egt;97:3) and excellent diastereoselectivity (&egt;94% de).

Carbohydrate-based chiral auxiliaries have proven effective in cycloadditions with (1).14 The auxiliary derived from 3-O-acryloyldihydro-D-glucal (eq 10; R = pivaloyl) afforded the (S)-cyclohexenecarboxylate (8:92 R/S), whereas the pseudoenantiomeric system, 3-O-acryloyldihydro-L-rhamnal (eq 11; R = pivaloyl), afforded the (R)-cycloadduct (95:5 R/S). Complexation of the titanium catalyst to each of the ester carbonyl oxygens was postulated to rigidify the acryloyl group, locking it in the conformation depicted. In both cases, cycloaddition presumably occurs to the less hindered face of the acrylate away from the bulky 4-O-pivaloyl group.

Chiral titanium-based catalysts have been used in asymmetric Diels-Alder reactions of (1). A mixture of TiCl4 and Titanium Tetraisopropoxide was used with a tartrate-derived auxiliary in the cycloaddition of (1) with a quinone (eq 12) to afford the expected bicyclic system in 88% yield and 63% ee.15 Other dienes underwent stereoselective cycloadditions with better asymmetric induction. A similar catalyst system was used in the cycloaddition of (1) with fumarate16 and acrylate17 derivatives. The catalyst was prepared by alkoxy exchange with the tartrate-derived auxiliary and Dichlorotitanium Diisopropoxide, and was treated with the cycloaddition partners at rt for 24 h to afford the cyclohexenecarboxylate in 81% yield and in 93% optical purity (eq 13). Other dienes underwent asymmetric cycloaddition with equal success. A model was proposed for the catalyst-dienophile complex.

The C2-symmetric hydrobenzoin complexed with TiCl4 promoted the cycloaddition of (1) with Dimethyl Fumarate to afford the cyclohexenedicarboxylate in 78% yield with a modest 60% ee (eq 14).18 Carboxylic ester dienophiles have typically participated ineffectively in asymmetric Diels-Alder reactions.

Applications in Synthesis.

Butadiene is a widely used reagent in organic synthesis. It is primarily used as the 4p participant in the Diels-Alder construction of carbocyclic and heterocyclic six-membered rings,2 although numerous other uses have been recorded.

Butadiene cycloaddition was a key step in the synthesis of constrained phenanthrenamine derivatives that are active as noncompetitive NMDA antagonists.19 Reaction of dihydronaphthalenecarboxylic acid with (1) in toluene at 110 °C in the presence of polymerization inhibitor afforded the tricyclic adduct in 60% yield (eq 15). Hydrogenation of the resulting double bond afforded the hydrophenanthrenecarboxylic acid, which was converted to a variety of tetracyclic structures where the carboxylate was converted to an amine by modified Curtius rearrangement.

Three reports have described the use of butadiene in the asymmetric construction of the C-28-C-34 fragment of the immunosuppressant FK-506.20-22 In the first report (eq 16), the acrylate ester of (S)-(+)-pantolactone was reacted with (1) in the presence of TiCl4 to afford the cyclohexenecarboxylate in excellent yield and in 91% de.20 In the second report, the same Diels-Alder reaction was performed with a chiral sultam auxiliary under EtAlCl2 catalysis to give the cyclohexenecarboxylate in 86% yield in 93% ee (eq 17).21 In the third report, an acryloyl-(S)-2-hydroxysuccinimide underwent cycloaddition with (1) under catalysis by TiCl4 to afford the cyclohexenecarboxylate in 85% yield in 98% ee (eq 18).22 The double bond of all three cycloadducts was subsequently converted to the anti-diol of FK-506. A cycloaddition reaction identical to that shown in eq 16 was used as a key step in the asymmetric synthesis of the cyclohexane ring of (+)-phyllanthocin.23 In this instance the cycloaddition proceeded in 70% yield and in 97% ee.

A b-pinene-derived dienophile was used as the 2p cycloaddition partner with (1) in an approach to the morphine skeleton (eq 19).24 Thermal cycloaddition occurred stereoselectively from the face opposite the substituted bridge to afford the adduct in 82% yield. Cycloaddition was also effected in lower yield under Lewis acid-catalyzed conditions (Cu(BF4)2, CH2Cl2, 25 °C, 12 h, 34%). Further elaboration of the cycloadduct afforded the cis-D6-1-octalone acetal possessing the required absolute configuration at three contiguous stereogenic centers for conversion to morphine-related compounds. In a synthetic approach to analogs of the potassium channel activator aprikalim, butadiene was used in a hetero Diels-Alder reaction for the construction of a thiopyran ring (eq 20).25 Thus reaction of the thiocarbonyl group of an a-thioketo ester (generated in situ) with (1) afforded the desired thiopyran in 65% yield.

An asymmetric Diels-Alder reaction of (1) with a phenylalaninol-derived auxiliary was used to construct the B-ring of (+)-compactin and (+)-mevinolin (eq 21).26 Cycloaddition of the (E)-crotonic acid derivative with butadiene in the presence of catalytic Et2AlCl afforded the desired cycloadduct in 56% yield and greater than 95% de. The auxiliary was removed and the desired cis-isomer of the 2-methyl-4-cyclohexenecarboxylate was obtained by base-promoted epimerization of the trans-isomer (65:35 cis/trans equilibrium mixture). Use of the corresponding (Z)-crotonoyl auxiliary was not examined as the (Z) configuration of the alkene is not preserved under the reaction conditions.27

A rapid and stereospecific construction of the 2-azabicyclo[3.3.1]nonane ring system characteristic of Strychnos alkaloids was initiated with a Diels-Alder reaction of b-nitrostyrene and (1) (eq 22).28 After reduction of the nitro group and N-acylation, the desired aminocyclohexene was obtained in 63% overall yield. Subsequent elaboration to the 2-azabicyclo[3.3.1]nonane system involved a high-yielding stereoselective Heck reaction. Butadiene sulfone was used for in situ generation of (1) in an approach to cephalotaxine analogs. In a key step, a b-nitrostyrene dienophile was treated with butadiene sulfone at 135 °C to afford the butadiene cycloadduct in 74% yield (eq 23).29

Miscellaneous Reactions.

The novel dienophile 2-trimethylsilylvinyl-9-BBN was shown to undergo facile Diels-Alder reaction with butadiene to afford the 2-trimethylsilylcyclohexenol in 85% yield after oxidation of the intermediate trialkylborane (eq 24).30 The cycloadduct was shown to be a precursor to 5-trimethylsilyl-1,3-cyclohexadiene and -1,4-cyclohexadiene, thus making the dienophile an acetylene equivalent.

Catalytic osmylation was used to convert 1,3-butadiene to a polyol with good control of relative stereochemistry (eq 25).31 Under standard osmylation conditions, (1) was converted to the 2,3-anti-tetraol in 80% yield in a 5:1 anti/syn ratio. The stereoselectivity of this reaction is consistent with previous findings on the osmylation of allylic alcohols and ethers.


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Robert S. Coleman & Henry A. Alegria

University of South Carolina, Columbia, SC, USA



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