Vinylcyclopropylacyl and polyeneacyl radicals. Intramolecular ketene alkyl radical additions in ring synthesis

Treatment of a variety of substituted vinylcyclopropyl selenyl esters, e.g. 11, with Bu(3)SnH-AIBN in refluxing benzene leads to the corresponding acyl radical intermediates, which undergo rearrangement and intramolecular cyclisations via their ketene alkyl radical equivalents producing cyclohexenones in 50-60% yield. By contrast, treatment of conjugated triene selenyl esters, e.g. 32, with Bu(3)SnH-AIBN produces substituted 2-cyclopentenones via intramolecular cyclisations of their ketene alkyl radical intermediates. Under the same radical-initiating conditions the selenyl esters derived from o-vinylbenzoic acid and o-vinylcinnamic acid undergo intramolecular cyclisations producing 1-indanone and 5,6-dihydrobenzocyclohepten-7-one respectively in 60-70% yields. A tandem radical cyclisation from the alpha,beta,gamma,delta-diene selenyl ester 31 provides an expeditious synthesis of the diquinane 35 in 69% yield.     

Unexpected dual orbital effects in radical addition reactions involving acyl, silyl and related radicals

Molecular orbital calculations reveal that acyl and silyl radicals add to numerous types of pi-systems through simultaneous SOMO-LUMO and LUMO-HOMO interactions of the radical with the radicalophile respectively.     

Synthesis of oxime bearing cyclophosphazenes and their reactions with alkyl and acyl halides

Two novel cyclophosphazenes containing oxime groups were prepared from the hexakis(4‐formylphenoxy)cyclotriphosphazene ( 2 ) and hexakis‐(4‐acetylphenoxy)cyclotriphosphazene ( 7 ). The reactions of these oximes with acetyl chloride, chloroacetyl chloride, methyl iodide, propyl chloride, mono‐ chloroacetone, and 1,4‐dichlorobutane were studied. Hexasubstituted compounds were obtained from the reactions of hexakis(4‐[(hydroxyimino)methyl]phenoxy)cyclotriphosphazene ( 3 ) with acetyl chloride ( 4 ) and chloroacetyl chloride ( 5 ); however, tetrasubstituted product was obtained from methyl iodide ( 6 ). Tetra‐ and trisubstituted products were obtained from the reactions of hexakis(4‐[(1)‐N‐hydroxyethaneimidoyl]phenoxy)cyclotriphosphazene ( 8 ) with acetyl chloride ( 9 ) and chloroacetyl chloride ( 10 ), respectively. All products were obtained in high yields. Pure and defined product could not be obtained from the reaction of 8 with methyl iodide, and could not be also obtained from the reactions of 3 and 8 with propyl chloride, monochloroacetone, and 1,4‐dichlorobuthane. The structures of the compounds were defined by elemental analysis, IR, ¹H, ¹³C, and ³¹P NMR spectroscopy. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:112–117, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20176     

Cobalt-catalyzed cross-coupling reactions of alkyl halides with allylic and benzylic Grignard reagents and their application to tandem radical cyclization/cross-coupling reactions

Details of cobalt-catalyzed cross-coupling reactions of alkyl halides with allylic Grignard reagents are disclosed. A combination of cobalt(II) chloride and 1,2-bis(diphenylphosphino)ethane (DPPE) or 1,3-bis(diphenylphosphino)propane (DPPP) is suitable as a precatalyst and allows secondary and tertiary alkyl halides--as well as primary ones--to be employed as coupling partners for allyl Grignard reagents. The reaction offers a facile synthesis of quaternary carbon centers, which has practically never been possible with palladium, nickel, and copper catalysts. Benzyl, methallyl, and crotyl Grignard reagents can all couple with alkyl halides. The benzylation definitely requires DPPE or DPPP as a ligand. The reaction mechanism should include the generation of an alkyl radical from the parent alkyl halide. The mechanism can be interpreted in terms of a tandem radical cyclization/cross-coupling reaction. In addition, serendipitous tandem radical cyclization/cyclopropanation/carbonyl allylation of 5-alkoxy-6-halo-4-oxa-1-hexene derivatives is also described. The intermediacy of a carbon-centered radical results in the loss of the original stereochemistry of the parent alkyl halides, creating the potential for asymmetric cross-coupling of racemic alkyl halides.     

Disproportionation reactions between alkyl and fluoroalkyl radicals. IV. Pentafluoroethyl and ethyl radicals

A new determination of the disproportionation/combination ratio for C₂F₅ and C₂H₅ radicals gives a value of Δ(C₂F₅, C₂H₅) = 0.24 ± 0.02, independent of temperature. The cross-combination ratio for the two radicals was found to increase with temperature and the significance of this is discussed in evaluating Δ.     

Disproportionation reactions between alkyl and fluoroalkyl radicals. VI. Difluoromethyl and n-propyl radicals

Cross-disproportionation to combination ratios for CF₂H and n-C₃H₇ radicals have been determined (the hydrogen acceptor radical is given first) to be Δ(n-C₃H₇, CF₂H) = 0.30 ± 0.01 and Δ(CF₂H, n-C₃H₇) = 0.057 ± 0.006.     

Synthesis of lactams by radical substitution reaction of alpha,beta-unsaturated acyl radicals at amine nitrogen

[reaction: see text] Substitution at nitrogen by alpha,beta-unsaturated acyl radicals took place accompanied by elimination of an alpha-phenethyl radical. This reaction led to the development of a new carbonylative annulation method for five- to seven-membered ring lactams.     

Disproportionation reactions between alkyl and fluoroalkyl radicals. V. Perfluoro-n-propyl and ethyl radicals revisited

A redetermination of the disproportionation/combination ratio for n–C₃F₇ and C₂H₅ radicals gives a value of Δ(n–C₃F₇, C₂H₅) = 0.13 ± 0.01, independent of the temperature. The radicals were produced by the photolysis of n–C₃F₇COC₂H₅. The previous determinations of this ratio are discussed and are found to be largely incorrect. The values for Δ(CF₃, C₂H₅) and Δ(C₂F₅, C₂H₅) are also re-evaluated, and the recommended values are 0.10 ± 0.02 and 0.12 ± 0.02, respectively. Systems involving perfluoroalkyl and ethyl radicals are complicated due to rapid perfluororadical addition to the ethylene formed in the disproportionation process. The extent of this reaction, and its consequences, are discussed and evaluated. The role of the propionyl (C₂H₅CO) radical in the room temperature photolysis is also assessed. However, it is found that the Δ values determined by the intercept method used in this work are not affected by the secondary reactions that occur. It is concluded that high cross-combination ratios are general to perfluoroalkyl-alkyl radical interactions. For C₃F₇ and C₂H₅ radicals the ratio is 2.7–2.8. Above 100°C ratios exceed 3 due to secondary reactions.     

Theoretical study on the isomerization behavior between alpha,beta-unsaturated acyl radicals and alpha-ketenyl radicals

[reaction: see text] Ab initio calculations using 6-311G**, cc-pVDZ, aug-cc-pVDZ, and a (valence) double-zeta pseudopotential (DZP) basis set, with (QCISD, CCSD(T)) and without (UHF) the inclusion of electron correlation, and density functional methods (BHandHLYP, B3LYP) predict that alpha,beta-unsaturated acyl radicals and alpha-ketenyl radicals exist as isomers. At the CCSD(T)/cc-pVDZ//BHandHLY/cc-pVDZ level of theory, energy barriers of 15.1 and 17.7-21.7 kJ mol(-)(1) are calculated for the isomerization of s-trans-propenoyl and s-trans-crotonoyl radical to ketenylmethyl and 1-ketenylethyl radical, respectively. Similar results are obtained for the reactions of s-trans isomers involving silyl, germyl, and stannyl groups with energy barriers (DeltaE++) of 12.2-12.4, 13.1-13.9, and 12.9-18.2 kJ mol(-)(1) at the CCSD(T)/DZP//BHandHLYP/DZP calculation, respectively. These results suggest that alpha,beta-unsaturated acyl radicals and alpha-ketenyl radicals are not canonical forms but are isomeric species that can rapidly interconvert.     

Disproportionation reactions between alkyl and fluoroalkyl radicals. II. Fluoro- and trifluoromethyl with ethyl radicals

Cross-disproportionation/combination ratios for CFH₂ and CF₃ with C₂H₅ radicals have been determined to be Δ = 0.032 ± 0.012 and δ = 0.098 ± 0.020, respectively, over the temperature range 25–75°C. For the pathway that yields CFH and C₂H₆, δ = 0.020 ± 0.005 at 25°C.     

Pteridines. Part LXXXV. Chemical synthesis of deoxysepiapterin and 6-acylpteridines by acyl radical substitution reactions

A new synthesis of deoxysepiapterin ( 2 ), one of the two yellow eye pigments of the Drosophila mutant sepia, is described. The synthetic approach makes use of a homolytic nucleophilic acylation of 7-(alkylthio)pteridine derivatives ( 11, 13, 15, 18, 20 ) leading to the corresponding 6-acyl derivatives ( 21–27 ). Desulfurizations have been achieved for the first time in the pteridine series using Raney-Co,Raney-Cu, or Cu? Al alloy in alkaline medium. Besides cleavage of the C(7)? S bond, further reductions of the C?O group at C(6) and the C(7)?N(8) bond are detected as side reactions leading to 6-(1-hydroxyalkyl) ( 34, 35, 42, 43 ) and 6-acyl-7,8-dihydro derivatives ( 2, 36, 37 ), respectively, The newly synthesized compounds have been characterized by elemental analysis, p_K determination, UV and ¹H-NMR spectra.     

Disproportionation reactions between alkyl and fluoroalkyl radicals. VII. Difluoromethyl with perfluoro-n-propyl and methyl radicals

Mixtures of 1,1,3,3-tetrafluoroacetone and perfluorodi-n-propyl ketone have been photolyzed together over the temperature range 50° to 200°C, and the disproportionation/combination ratio for n-C₃F₇ and CF₂H radicals has been determined to be Δ(n-C₃F₇, CF₂H) = 0.072 ± 0.003. A reevaluation of existing data on CH₃ and CF₂H radicals leads to a value of Δ(CH₃, CF₂H) = 0.35. The large variations in Δ for the reactions of alkyl and perfluoroalkyl radicals with CF₂H radicals are discussed. © John Wiley & Sons, Inc.     

An ab initio and DFT study of some halogen atom transfer reactions from alkyl groups to acyl radical

Ab initio calculations using the 6-311G**, cc-pVDZ, and (valence) double-zeta pseudopotential (DZP) basis sets, with (MP2, QCISD, CCSD(T)) and without (HF) the inclusion of electron correlation, and density functional (BHandHLYP, B3LYP) calculations predict that the transition states for the reaction of acetyl radical with several alkyl halides adopt an almost collinear arrangement of attacking and leaving radicals at the halogen atom. Energy barriers (DeltaE(double dagger)) for these halogen transfer reactions of between 89.2 (chlorine transfer from methyl group) and 25.3 kJ mol(-1) (iodine transfer from tert-butyl group) are calculated at the BHandHLYP/DZP level of theory. While the difference in forward and reverse energy barriers for iodine transfer to acetyl radical is predicted to be 15.1 kJ mol(-1) for primary alkyl iodide, these values are calculated to be 6.7 and -4.2 kJ mol(-1) for secondary and tertiary alkyl iodide respectively. These data are in good agreement with available experimental data in that atom transfer radical carbonylation reactions are sluggish with primary alkyl iodides, but proceed smoothly with secondary and tertiary alkyl iodides. These calculations also predict that bromine transfer reactions involving acyl radical are also feasible at moderately high temperature.     

Catalytic, asymmetric synthesis and diastereoselective aldol reactions of dipropionate equivalents

The dimer of methylketene can be conveniently prepared in one step and high enantiomeric excess from propionyl chloride, using a catalytic amount of a silylated cinchona alkaloid as a source of chirality. Opening of the dimer with a lithiated sulfonamide affords a beta-ketosulfonimide, which undergoes Sn(II)-mediated aldol reactions to diastereoselectively afford the anti,syn-aldol adduct. Alternatively, reduction of the dimer to the beta-hydroxy ketone, followed by acylation, affords a beta-acyloxyl ketone that undergoes diastereoselective, dialkylboron chloride-mediated aldol reactions to produce the anti,anti-aldol adduct.     

A Quantitative study of alkyl radical reactions by kinetic spectroscopy. Part I. Mutual combination of methyl radicals and combination of methyl radicals with nitric oxide

Combination reactions of the methyl radical have been studied by following the decay of the absorbance of the methyl radical during the course of the reaction by means of kinetic spectroscopy. The limiting values of the second-order rate constants at high pressure were determined for two reactions at room temperature: The extinction coefficient of the methyl radical was found to have a maximum value of (1.02 ± 0.06) X 10⁴ 1 mole^?1 cm^?1 at 216.4 nm. Integration of the extinction coefficient over the absorption band of the methyl radical gave an oscillator strength of 1.0 X 10^?2.     

Generation and reactions of 2-lithio-2-substituted-1,3-benzodithioles; new,convenient acyl carbanion equivalents

The reaction ofBuⁿLi with 2-substituted-1,3-benzodithioles yields anions which react predictably with organic electrophiles to yield products in which the protected carbonyl group is readily unmasked. The anions constitute useful acyl carbanion equivalents.     

Rearrangement of cyclopropyl,substituted vinyl and alkyl groups to divalent carbon.

The relative carbenic migratory abilities of cyclopropyl, β,β-dimenthylvinyl, methyl, ethyl and isopropyl group have been determined.     

Cobalt N-heterocyclic carbene alkyl and acyl compounds: synthesis, molecular structure and reactivity

The N-heterocyclic-carbene containing cobalt carbonyl compound [Co(IMes)(CO)3(Me)] (IMes = 1,3-bis(2,4,6-trimethylphenyl)-imidazol-2-ylidene), 1, has been synthesised by tertiary phosphine displacement from [Co(PPh3)(CO)3(Me)]. Subsequent carbonylation afforded the acyl derivative [Co(IMes)(CO)3(COMe)], 2. Similarly, the compound [Co(IMes)(CO)3(COEt)], 3, has been synthesised. The compounds 2 and 3 have been shown to react with dihydrogen to form the cobalt hydride compound [Co(IMes)(CO)3(H)], 4. The molecular structures of compounds 1 and 2 have been determined.