Intermolecular reactions with alkenes

Intramolecular reactions with alkenes. While the intermolecular reaction is limited to unhindered alkenes, the intramolecular version permits the participation of even hindered substituted alkenes, and various cyclic compounds are prepared by the intramolecular Heck reaction. Particularly the... 

The photochemical generation of hydroxy-o-quinodimethanes from o-alkylbenz-aldehydes may be followed by a thermal Diels-Alder reaction with alkenes (Scheme 9.33) [54]. This reaction is effective in both intermolecular and intramolecular modes, and has been applied to the synthesis of various natural products [55],... 

It is as efficient as Bu3SnH for initiation of intermolecular or intramolecular radical reactions with alkenes.3... 

The next selectivity issue, exo/endo preferences, can be predicted for both the ortho and meta modes of cycloaddition on the basis of secondly orbital interactions (FMO treatment) and by electrostatic considerations involving polarized species (54) and (27). In general, intermolecular reactions with simple al-kenes proceed with endo selectivity. Heteroatom-substituted or polarized alkenes (equation 11) give exolendo mixtures, whose composition can be explained by electrostatic considerations. Intramolecular cycloadditions of simple alkenes and arenes joined by a three-atom tether generally proceed with high exo selectivity due in part to orbital alignment effects. In all cases, alkene geometry is preserved, except for sterically encumbered alkenes, in which case excitation transfer from the arene to the alkene can occur. 

In the case of the 1,2,3-butatriene 2-episulfide bearing less-hindered substituents such as (132) and its S-oxide (146), intermolecular reaction with a variety of dienophiles was realized. In terms of strained alkenes, [2 + 4] addition of (132) and (146) would emerge as a powerful method for introducing a double bond into a three-membered ring fused to a six-membered ring. The compound... 

Fused cyclopropanes are obtained by intramolecular cyclopropanations or by intermolecular reactions with cyclic alkenes or aromatic derivatives. The phosphoryl carbenes are the only phosphorus-substituted carbenes used in these reactions. 

The ene and Prins reactions are not mechanistically distinct. Coverage will therefore be organized by the nature of the carbonyl compound, with intermolecular reactions presented first, followed by intramolecular reactions. The emphasis will be on material published since the field has been reviewed " and on examples demonstrating the stereo-, regio- and chemo-selectivity of these reactions. Coverage is restricted to the addition of carbonyl and thiocarbonyl compounds to simple alkenes. Addition of carbonyl compounds to vinylsilanes, allylsilanes and enol ethers is covered in the following chapters. Addition of imines and iminium compounds to alkenes is presented in Part 4 of this volume. Ene reactions with alkenes and alkynes as enophiles are covered in Volume 5, Chapter 1.1. Use of aldehydes and acetals as initiators for polyene cyclizations is covered in Volume 3, Chapter 1.6. 

Due to the presence of these resonance forms in azomethine ylids, reaction with alkenes often leads to mixtures of regioisomeric cycloadducts. Resonance stabilizing substituents are usually employed to enhance the regioselectivity. Intramolecular reactions usually favor only one mode of addition. An example of an intermolecular reaction is taken from Williams synthesis of spirotryprostatin B,372 in which 5,6-diphenylmor-pholin-2-one (473) reacted with the aldehyde shown to give a mixture of ( )- and (Z)-azomethine ylids (474). This product was generated in situ with oxindole 475, and [3-i-2]-cycloaddition product 476 was obtained in 82% yield. 

Reactions with conjugated enynes as dienes in Diels-Alder reactions yield cyclohexadiene or benzene products on reaction with alkene or alkyne dienophiles, respectively. These reactions proceed via a stepwise mechanism to avoid formation of a cyclic allene and are referred to as dehydro-Diels-Alder reactions. In 2008, Barluenga and Aguilar demonstrated that gold catalysts promote intermolecular hetero-dehydro-Diels-Alder reactions between dienynes and nitriles. Dienyne 99 combines with phenyinitrile (100) to afford substituted pyridine 101. ... 

A more reactive yV-sulfinyl compound, A sulfinylnonafluoro butanesulfonamide, undergoes intermolecular ene reactions with alkenes over 10 times faster than the corresponding tosyl deiiva tive (eq 7). ... 

The in situ generation of nitrile oxides 119 and subsequent intra- or intermolecular 1,3-dipoIar cycloaddition reactions with alkenes and alkynes represent one of the most exploited strategies for the preparation of diverse isoxazoline 121 and isoxazole 120 derivatives. Ciufolini et al. [89] reported that PIDA in combination with a substoichiometric amount of TFA efficiently oxidize aldoximes 118 to nitrile oxides 119, which were trapped in situ with olefins to afford... 

In addition to the iminium-salt-based chemistry and to cross-coupling processes, aqueous formaldehyde can also be used as the carbonylated substrate in the Prins reaction, an intermolecular ene-type acid-catalyzed reaction with alkenes providing 1,3-dioxanes (Adams and Bhatnagar, 1977). 

Addition of NBS to an alkene in the presence of aqueous sodium azide affords fair yields of the corresponding /3-bromoazides, which can be converted by lithium aluminum hydride reduction to aziridines. Intermolecular reactions of alkenes with NBS and weaker nucleophiles can be achieved if conducted under anhydrous conditions to avoid the facile bromohydration reaction. In this manner, bromofluorination of alkenes has been extensively... 

A review of arene-cluster compounds, including their reactions with alkenes to afford unusual cluster alkene complexes, has been published and the intramolecular and intermolecular bonding in benzene cluster isomers has been investigated using molecular orbital calculations . ... 

Stahl and Sheldon have shown how oxidations can be driven by air as primary oxidant, or source of stochiometric oxidizing power. Like the catalysts in this subsection, biological oxidases are enzymes that use O2 but do not incorporate its O atoms into the substrate. For example, Pd(OAc)2-pyridine is active for alcohol oxidation, intramolecular hetero- and carbocyclization of alkenes, intermolecular O-C and C-C coupling reactions with alkenes, and oxidative C-C bond cleavage of tertiary alcohols. A pathway for alcohol oxidation is shown in Eq. 9.27. Normally a 4e process, reduction of O2 can be hard to couple with oxidation of the catalytic intermediates, processes that often proceed in 2e steps. In this case, intermediate rj -peroxo Pd(II) complexes can be formed from reaction of Pd(0) intermediates with O2, which thus acts as a 2e oxidant. 

Iridium The intermolecular hydroamination of unactivated C=C bonds in ct-olefins (RCH=CH2) and bicycloalkenes (norbornene and norbornadiene) with arylamides (ArCONH2) and sulfonamides has been attained upon catalysis by chiral iridium complexes (PP)IrHCl(NHCOAr)(NH2COAr) [PP = chiral bidentate diphosphine]. Mechanistic studies identified the product of N-H bond oxidative addition and coordination of the amide as the resting state of the catalyst. Rapid, reversible dissociation of the amide precedes reaction with the alkene, but an intramolecular, kinetically significant rearrangement of the species occurs before the reaction with alkene. ... 

Takechi, H. and Machida, M., Photoreactions of thiobarbiturates. Intermolecular cycloaddition with alkenes and ring contraction reaction of trithiobarbiturate, Chem. Pharm. Bull, 45,1,1997. Oda, K., Takahashi, H., and Machida, M., Photochemical transformation of trithiobarbiturate into thiohydantoin and imidazolinothiophene derivatives, Heterocydes, 50, 159, 1999. 

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