1657-60-9

Previously it was reported that activation of tBu2Zn by [(TMEDA)Na(μ-dpa)]2led to tert-butylation of benzophenone at the challenging para-position, where the sodium amide functions as a metalloligand towards tBu2Zn manifested in crystalline [{(TMEDA)Na(dpa)}2ZntBu2] (TMEDA is N,N,N′,N′-tetramethylethylenediamine, dpa is 2,2′-dipyridylamide). Here we find altering the Lewis donor or alkali metal within the metalloligand dictates the reaction outcome, exhibiting a strong influence on alkylation yields and reaction selectivity. Varying the former led to the synthesis of three novel complexes, [(PMDETA)Na(dpa)]2, [(TMDAE)Na(dpa)]2, and [(H6-TREN)Na(dpa)], characterised through combined structural, spectroscopic and theoretical studies [where PMDETA is N,N,N′,N′′,N′′-pentamethyldiethylenetriamine, TMDAE is N,N,N′,N′-tetramethyldiaminoethylether and H6-TREN is N′,N′-bis(2-aminoethyl)ethane-1,2-diamine]. Each new sodium amide can function as a metalloligand to generate a co-complex with tBu2Zn. Reacting these new co-complexes with benzophenone proved solvent dependent with yields in THF much lower than those in hexane. Most interestingly, sub-stoichiometric amounts of the metalloligands [(TMEDA)Na(dpa)]2and [(PMEDTA)Na(dpa)]2with 1 : 1, tBu2Zn-benzophenone mixtures produced good yields of the challenging 1,6-tert-butyl addition product in hexane (52% and 53% respectively). Although exchanging Na for Li gave similar reaction yields, the regioselectivity was significantly compromised; whereas the K system was completely unreactive. Replacing tBu2Zn with (Me3SiCH2)2Zn shut down the alkylation of benzophenone; in contrast, tBuLi generates only the reduction product, benzhydrol. Zincation of the parent amine dpa(H) generated the crystalline product [Zn(dpa)2], as structurally elucidated through X-ray crystallography and theoretical calculations. Although the reaction mechanism for the alkylation of benzophenone remains unclear, incorporation of the radical scavenger TEMPO (2,2,6,6-tetramethylpiperidine-N-oxyl radical) into the reaction system completely inhibits benzophenone alkylation.

Undercover agent: Masquerading as a simple donor-acceptor complex (1), sodium amide substoichiometrically activates tBu2Zn for the challenging 1,6-addition of a tert-butyl group to benzophenone. In contrast, the nonactivated tBu2Zn is ineffectual. Copyright

1,3-Dithianyl cation radicals having α-hydroxy-neopentyl or similar groups in position 2, which are generated via oxidative photoinduced electron transfer, undergo anomalous fragmentation necessitating refinement of the accepted mechanism. Experimental and computational data support a rationale in which proton abstraction from the hydroxy group in the initial cation radical does not cause a Grob-like fragmentation, but rather produces a neutral radical species, the alkoxy radical, that undergoes fragmentation in either direction, i.e., cleaving the C-C bond to dithiane or to the tertiary alkyl group.

Competition kinetics are useful for estimation of the reactivities of Grignard reagents if the reaction rates do not differ widely and if exact rates are not needed. If the rate of mixing is slower than the rate of reaction, the ratios between the rates of fast and slow reagents are found to be too small. This is concluded from experiments in which results obtained by competition kinetics are compared with results obtained directly by flow stream procedures. A clearer picture of the reactivity ratios is obtained when the highly reactive reagent is highly diluted with its competitor. A fast reagent may account for almost all the product even when present as only 1 part in 100 parts of the competing agent. In this way allylmagnesium bromide is estimated to react with acetone, benzophenone, benzaldehyde, and diethylacetaldehyde ca. 1.5 × 105 times faster than does butylmagnesium bromide. The rates found for the four substrates do not differ significantly, and it seems possible that there is a ceiling over the rate of reaction of this reagent, for example, caused by diffusion control. This may explain that competition kinetics using allylmagnesium bromide have failed to show kinetic isotope effects or effects of polar substituents with isotopically or otherwise substituted benzophenones. A recently reported α-deuterium secondary kinetic isotope effect for the reaction of benzaldehyde with allylmagnesium bromide was observed at -78°C, but was absent at room temperature. It is suggested that the reaction of benzophenone and benzaldehyde with allylmagnesium bromide has a radical-concerted mechanism since no radical-type products are produced and since no color from an intermediate ketyl is observed even at -78°C.

The 1,6-to 1,2-addition product ratios of the Grignard reactions of benzophenone with t-, s- and n-C4H9MgCl have been compared with the corresponding ratios obtained by the electrolysis of benzophenone in presence of t-, s- and n-C4H9S+(CH3)2, ClO4-in THF. The Grignard reaction ratios 0.81, 0.50 and 0.19, respectively, were obtained whereas the corresponding electrolysis ratios were 2.26, 1.23 and 1.61. From this comparison of product ratios it is concluded that none of the Grignard reactions of benzophenone proceeds through a complete free coupling process of benzophenone radical anions and butyl radicals. The ET character of the Grignard reactions of benzophenone with t-, s- and n-C4H9MgCl was estimated to be 65, 61 and 26%, respectively.

We designed various dialkylzinc hydride 'ate' complexes, prepared from dialkylzinc and metal hydride, and investigated the reactivities (and the transference aptitude of ligands) of these zincates toward benzophenone. The results clearly reveal that dimethylzinc hydrides are the most powerful and selective zincates for the reduction of the carbony1 group. This complex reagent turned out to be effective for the reduction of esters and amides as well as aldehydes and ketones to the corresponding alcohols and amines with good to excellent yields under mild conditions. Furthermore, the method was successfully used for the highly selective 1,2-reduction of α,β-unsaturated carbonyl compounds, the regioselective ring-opening reduction of epoxides, and the chemoselective reduction of aldehydes in the presence of ketones. We also discuss and clarify the active species and the mechanism of this reduction using the diastereoselective reductions of some carbonyl compounds with an adjacent chiral center. Also, this reducing system was found to constitute a powerful tool for the stereoselective synthesis of syn- and anti-1,2-diols. Moreover, we developed the catalytic version of this reducing system. The LiH-Me2Zn-ultrasound system proved to be effective not only for the catalytic reduction of the carbonyl compounds and epoxides but also for the partial reduction (the conversion) of carboxylic acids to aldehydes. This system is a very attractive method for several reasons (good availability, low cost, and easy operation) and would be particularly useful for large- scale reductions.

Thermolysis of di(1-adamantyl)-tert-butylmethanol (2a) in toluene at 145-185 deg C gives mainly bibenzyl, di(1-adamantyl) ketone, di(1-adamantyl)methanol, and the cross-product, 1,1-di(1-adamantyl)-2-phenylethanol.In the presence of benzophenone (BP) or benzenethiols as hydrogen-accepting and hydrogen-donating radical scavengers, respectively, the di(1-adamantyl)methanol/di(1-adamantyl) ketone ratio tends to steady values as the scavenger/2a ratio is increased, while the cross-product disappears.At 165 deg C the secondary alcohol minimum is 8percent (BP) and the ketone minimum 11percent (thiol).These represent the contributions of geminate hydrogen atom transfer reactions to the overall yields, i.e., the cage effects.With BP the major cross-product is 1,1,2-tri-phenylethanol.Products from the self- and cross-reactions of benzyl and thiyl radicals are found when thiol is present, the diaryl disulfide predominating at high thiol concentration.In both cases, cross-products resulting from reaction of the tert-butyl radical with the scavenger-derived radical are detected in small amounts, being of greater importance in deuteriated toluene.The tert-butyl radical is considered, therefore, to be less reactive in hydrogen atom abstraction than the 1-adamantyl radical.Cage effects for other di(tert-alkyl)-tert-butylmethanols that thermolyze with exclusive t-Bu-C bond fission have also been measured and the product composition of the scavenger-free reaction interpreted by kinetic simulation based on the steady state approximation.Rate constants for hydrogen abstraction by the tert-butyl radical from toluene are not accurately determined by this procedure but seem, nevertheless, to indicate that the literature value (14.4 M-1s-1 at 48 deg C) is an overestimate. Solvent hydrogen abstraction by the ketyl radical shows a small but well-defined steric effect.

Kinetic measurements have shown that the addition of Grignard reagents to α,β-unsaturated carbonyl compounds takes place either by a concerted mechanism or by a homolytic mechanism.Phenylmagnesium bromide, which is incapable of homolysis, reacts rapidly in a 1,4-fashion if an s-cis conformation exists between the C=C and the C=O bonds, but only 1,2-addition takes place if the conformation is s-trans.tert-Butylmagnesium bromide is unsuited to the concerted reaction, but 1,4-addition takes place via homolysis.Primary and secondary Grignard reagents, like phenyl, react rapidly in a concerted manner with s-cis substrates, but unlike phenyl, these Grignard reagents may, with s-trans substrates, produce some 1,4-adduct via the homolytic mechanism.

The carbonylation of a THF solution of aryllithium (aryl = Ph, o-anisyl) in the presence of an alkyl bromide, RBr; at atmospheric pressure and -78 deg C, affords diarylalkylcarbinols in good yields.Alkyl chlorides do not react under similar experimental conditions.This feature makes the reaction particularly useful for the synthesisof alcohols functionalized in the alkyl chain through subsequent reactions of the diaryl(chloro)alkylcarbinols.The procedure can also be adapted to afford substituted cyclic ethers.If the reaction is carried out in the presence of dibromoalkanes, only one bromine atom reacts, affording diaryl(bromo)alkylcarbinols which are useful intermediates.With secondary and tertiary alkyl bromides diaryl alkyl ethers are obtained in variable yields.

α-Amino carbanion equivalents (=C(1-)NH2) and α-hydrazino anion equivalents (=C(1-)NHNH2) are readily accessible from the C-alkylation products of t-butyldiphenylmethylhydrazones; these azoalkanes can be efficiently transformed into amines, hydrazines, and also alkanes under mild reaction conditions.

The radical Ph2C.-tBu (1) dimerizes giving reversibly the quinonoid derivative 3, and not the ethane-like 2 as reported in the literature.In equilibrium there are less radicals 1 than in the case of triphenylmethyl, ΔHdiss = 18.5 +/- 2 kcal/mol for 3.Both the radical 1 and its dimer 3 are rapidly oxidized by oxygen. 1 gives the dialkyl peroxide 6 which fragmentates already at 20 deg C mainly to benzophenone and tBu., 3 leads to the ketone 7, probably via the hydroperoxide 10. 3 rearranges catalysed by acid and by base as well via a 1,5-hydrogen migration forming the benzenoid derivative 4.Preparative and ESR details are given.

The formation of products 2, 3 and 4(a-l) from both the reaction of εta2-bezophenone zirconocene 1 with alkyl halides and the thermolysis of the α-(Cp2ZrCl)-substituted benzhydrylmethylether 9, the latter proceeding with anchimeric assistance of the metal, can be understood assuming a stepwise reaction path through radical intermediates.The proposed intermediate transition-metal benzophenone ketyl 12 exhibits a reaction pattern differing from analogous main-group-metal ketyls.

The carbonylation of ArLi (Ar = Ph, o-anisyl) in the presence of alkyl bromides affords diarylalkylcarbinols in good yields.The reaction may be used to obtain alcohols functionalized in the alkyl chain; it can also be adapted to afford substituted tetrahydrofurans.

Reversal of the carbonyl activity of benzophenone, serving as electron donor in single-electron transfer processes and acting as a proton acceptor through the 'carbonyl'carbon atom, is observed upon η2 -complexation to zirconocene.