Alkylaluminum halides react with Brønsted acids to liberate an alkane and generate a new Lewis acid. Using these reagents, Lewis acid catalyzed reactions can be run under aprotic conditions, even when acidic protons are produced in the reaction. The use of these reagents for Lewis acid catalyzed ene, Diels-Alder and cycloaddition reactions and Claisen rearrangements is described. These reagents are also useful initiators for cation-olefin addition reactions. In some cases the alkyl groups react as nucleophiles. While this is often undesirable, addition of an alkyl group to carbenium ion intermediates provides novel classes of compounds.
54. Snider, B. B.; Duncia, J. V. “Stereospecific Syntheses of both Diastereomers of (±)-2-Amino-4-methyl-5-hexenoic Acid” J. Org. Chem. 1981, 46, 3223-3226. http://dx.doi.org/10.1021/jo00329a015
Both diastereomers of 2-amino-4-methyl-5-hexenoic acid have been synthesized stereospecifically from methyl (2R*,4S*)-2-bromo-4-methyl-5-hexenoate, the product of the EtA1C12-catalyzed ene reaction of methyl a-bromoacrylate and trans-2-butene. This synthesis establishes the stereochemistry of the ene reaction and establishes that the amino acid isolated from a Streptomyces fermentation is the (2S*,4S*) isomer..
53. Snider, B. B. “Synthesis of Allylic Sulfoxides from Alkenes by Dichloroethylaluminum Catalyzed Ene Reaction with p-Toluenesulfinyl Chloride” J. Org. Chem. 1981, 46, 3155-3157. http://dx.doi.org/10.1021/jo00328a043
Ethylaluminum dichloride (EtAlCl2) catalyzes the ene reaction of alkenes with arylsulfinyl chlorides to give allylic sulfoxides since EtAlCl2 acts as a proton scavenger as well as a Lewis acid, reacting with the hydrogen chloride produced in the reaction to give aluminum trichloride and ethane.
52. Batcho, A. D.; Berger, D. E.; Uskokovic, M. R.; Snider, B. B. “C-20 Stereospecific Introduction of a Steroid Side Chain” J. Am. Chem. Soc. 1981, 103, 1293-1295. http://dx.doi.org/10.1021/ja00395a085
51. Snider, B. B.; Phillips, G. B. “Dimethylaluminum Chloride Catalyzed Reactions of Methyl α-Cyanoacrylate with Alkenes” J. Org. Chem. 1981, 46, 2563-2566. http://dx.doi.org/10.1021/jo00325a025
The methyl α-cyanoacrylate-Me2AlCl complex reacts with alkenes to give a zwitterion. Ring closure on carbon gives a cyclobutane with ~90% retention of alkene stereochemistry, ring closure on oxygen gives a dihydropyran, and a 1,5-hydrogen shift gives an ene adduct.
50. Karras, M.; Snider, B. B. “Alkylaluminum Chloride Induced Cyclization of Unsaturated Carbonyl Compounds” J. Am. Chem. Soc. 1980, 102, 7951-7953. http://dx.doi.org/10.1021/ja00547a031
49. Snider, B. B. “Lewis-Acid Catalyzed Ene Reactions” Acc. Chem. Res. 1980, 13, 426-432. http://dx.doi.org/10.1021/ar50155a007
48. Snider, B. B.; Kirk, T. C.; Roush, D. M.; Gonzalez, D. “Lewis Acid Catalyzed Ene Reactions of Ethynyl p-Tolyl Sulfone” J. Org. Chem. 1980, 45, 5015-5017. http://dx.doi.org/10.1021/jo01313a001
47. Snider, B. B.; Spindell, D. K. “Lewis Acid Catalyzed [2 + 2] Cycloaddition of Methyl 2,3-Butadienoate to Alkenes” J. Org. Chem. 1980, 45, 5017-5020. http://dx.doi.org/10.1021/jo01313a002
Methyl 2,3-butadienoate (1) undergoes EtAICl2-catalyzed stereospecific [2 + 2] cycloadditions with alkenes to give methyl cyclobutylideneacetates in good yield. The stereospecificity and ratios of E and Z isomers suggest a [p2s + p2a] cycloaddition of the ester-EtA1Cl2 complex analogous to that of ketenes.
46. Rodini, David J.; Snider, B. B. “Dimethylaluminum Halide Induced Reactions of Formaldehyde with Alkynes. Synthesis of α-Allenic Alcohols and Z-3-Chloroallylic Alcohols” Tetrahedron Lett. 1980, 21, 3857-3860. http://dx.doi.org/10.1016/0040-4039(80)80199-7
The CH2O·Me2AlCl complex reacts with terminal alkynes to give α-allenic alcohols via a formal ene reaction and Z-3-chloroallylic alcohols via a stereospecifically syn Friedel-Crafts addition.
45. Snider, B. B.; Rodini, D. J. “Dialkylaluminum Chloride-Catalyzed Ene Reactions of Aldehydes. Synthesis of Ipsenol” Tetrahedron Lett. 1980, 21, 1815-1818. http://dx.doi.org/10.1016/S0040-4039(00)92787-4
Dimethylaluminum chloride which is a mild Lewis acid and a proton scavenger, catalyzes the ene reactions of aliphatic and aromatic aldehydes. Proton initiated rearrangements do not occur, since the alcohol-Lewis acid complex formed in the ene reaction rapidly to give methane and a non-acidic aluminum alkoxide.
44. Snider, B. B.; Duncia, J. V. “Stereoselective and Regioselective Ene Reactions of Methyl α-Chloroacrylate” J. Am. Chem. Soc. 1980, 102, 5926-5928. http://dx.doi.org/10.1021/ja00538a047
43. Snider, B. B. “Diels-Alder Reactions of 2-Acetyl-2-cyclohexenone with Enol Ethers and Enamines” Tetrahedron Lett. 1980, 21, 1133-1136. http://dx.doi.org/10.1016/S0040-4039(01)83932-0
2-Acetyl-2-cyclohexenone (2) undergoes inverse electron demand Diels-Alder reactions with enol ethers at 25°C. The adduct in which the oxygen adds endo is favored. Trans substituted enol ethers are ≈ 35 times as reactive as the cis isomer. Enamines react immediately with 2 at 25°C.
42. Snider, B. B.; Roush, D. M.; Rodini, D. J.; Gonzalez, D.; Spindell, D. “Lewis Acid Catalyzed Reactions of Acetylenic Esters with Alkenes. Stereochemistry and Regiochemistry” J. Org. Chem. 1980, 45, 2773-2785. http://dx.doi.org/10.1021/jo01302a007
The Lewis; acid catalyzed reaction of methyl chloropropiolate or dimethyl acetylenedicarboxylate with alkenes leads to ene reactions and/or stereospecific [2 + 2] cycloaddition. Ethylaluminum dichloride was found to be a very effective catalyst since it is a strong Lewis acid and an HCl scavenger. With trisubstituted alkenes the ene reaction is regiospecific. A hydrogen is transferred from the alkyl group trans to the alkenyl hydrogen. The regio- and stereoselectivity of the ene reactions of methyl chloropropiolate, methyl propiolate, and dimethyl acetylenedicarboxylate are described. From cyclohexenes, pseudoaxial hydrogens are transferred exclusively. The relative reactivity of alkenes was found to be 1,l-disubstituted > trisubstituted >> monosubstituted and 1,2-disubstituted. The ene adducts and cyclobutenecarboxylates derived from methyl chloropropiolate undergo substitution reactions with organocuprates and can be hydrolyzed to b-keto esters and substituted dimethyl glutarates, respectively.
41. Snider, B. B.; Rodini, D. J.; Van Straten, J. “Lewis Acid Induced Conjugate Addition of Alkenes to α,β-Unsaturated Ketones or Aldehydes” J. Am. Chem. Soc. 1980, 102, 5872-5280. http://dx.doi.org/10.1021/ja00538a028
α,β-Unsaturated ketones or aldehydes form a 1 :2 complex with ethylaluminum dichloride that reacts with alkenes either intermolecularly or intramolecularly to give a zwitterion. The zwitterion collapses reversibly to a cyclobutane in geometrically favorable cases and undergoes hydride and alkyl shifts to generate α,β-unsaturated carbonyl compounds. The intramolecular reactions proceed with high regio- and stereospecificity. The reaction is quite general for a variety of enone and alkene substitution patterns. Other Lewis acids do not give similar reactions. Use of less than 1 equiv of EtAICl2 in intramolecular reactions gives concerted ene reactions in geometrically favorable cases and complex mixtures of products where an ene reaction
40. Snider, B. B.; Duncia, J. V. “Intramolecular Diels-Alder and Ene Reactions of 2,6-Dimethyl-2,7-octadienal” J. Org. Chem. 1980, 45, 3461-3464. http://dx.doi.org/10.1021/jo01305a018
2,6-Dimethyl-2,7-octadienal (1) undergoes a BF3-catalyzed reaction to give exo-4,8-dimethyl-2-oxabicyclo-[3.3.l]non-3-ene (4) in 49% yield. Adduct 4 is probably formed by a Lewis acid catalyzed inverse-electron-demand Diels-Alder reaction in which the α.β-unsaturated aldehyde functions as the diene.