Yudong Cai

The mechanism of polarity-reversal catalysis as involved in the radical-chain reduction of alkyl halides using the silane–thiol couple

The mechanism by which thiols promote the radical-chain reduction of alkyl halides by a variety of simple silanes, such as Et3SiH and Ph3SiH, has been investigated in detail. Kinetic studies of the thiol-catalysed reduction of 1-bromooctane and of 1-chlorooctane by Et3SiH in cyclohexane at 60 °C are consistent with a mechanism that involves reversible abstraction of hydrogen by the thiyl radical from the silane, followed by abstraction of halogen from the octyl halide by the resulting triethylsilyl radical and quenching of the derived octyl radical by the thiol to give octane. On the basis of this mechanism, rate constants for abstraction of hydrogen from Et3SiH by the adamantane-1-thiyl radical (kXSH) and for transfer of hydrogen in the reverse direction (kSiH) were determined as 3.2 × 104 M−1 s−1 and 5.2 × 107 M−1 s−1, respectively, at 60 °C. The equilibrium constant kXSH/kSiH is thus 6.2 × 10−4 at 60 °C and corresponds to ΔrH ≈ ΔrG = +20.4 kJ mol−1 for abstraction of hydrogen from Et3SiH by 1-AdS˙, implying that the Si–H bond in the silane is stronger by ca. 20 kJ mol−1 than the S-H bond in the alkanethiol. The silanethiol (ButO)3SiSH was found to be a more effective catalyst than 1-AdSH, because kXSH is greater (1.3 × 105 M−1 s−1) while kSiH is very similar (5.1 × 107 M−1 s−1). The value of kXSH/kSiH is now 2.6 × 10−3 at 60 °C and thus the S–H bond in this silanethiol is stronger by ca. 4 kJ mol−1 than that in 1-AdSH. The proposed mechanism for alkyl halide reduction is strongly supported by kinetic studies of the thiol-catalysed H/D-exchange between R3SiH/D and XSH/D and the thiol-catalysed racemisation of (S)-ButMePhSiH, radical-chain processes that provide independent confirmation of the values of kXSH derived from octyl bromide reduction. The value of ΔrH determined in this work indicates that abstraction of hydrogen from Et3SiH by an alkanethiyl radical in cyclohexane solvent is ca. 11 kJ mol−1 less endothermic than implied by the difference in the currently-favoured experimental gas-phase dissociation enthalpies for the Et3Si–H and MeS–H bonds.

Formation of silanethiols by reaction of silanes with carbonyl sulfide: implications for radical-chain reduction of thiocarbonyl compounds by silanes

Abstract Carbonyl sulfide reacts with organosilanes at 60–85°C, in the presence of a radical initiator, to give the corresponding silanethiols. Triphenylsilane is confirmed as an excellent replacement for tributyltin hydride in the Barton–McCombie deoxygenation of alcohols via their xanthates under mild conditions. Reduction of xanthates by silanes can produce COS as a by-product, leading to the in situ formation of silanethiol that will then act as a protic polarity-reversal catalyst for the reduction.

Carbon–carbon bond formation by radical addition–fragmentation reactions of O-alkylated enols

Alpha-tert-butoxystyrene [H2C=C(OBut)Ph] reacts with alpha-bromocarbonyl or alpha-bromosulfonyl compounds [R1R2C(Br)EWG; EWG =-C(O)X or -S(O2)X] to bring about replacement of the bromine atom by the phenacyl group and give R1R2C(EWG)CH2C(O)Ph. These reactions take place in refluxing benzene or cyclohexane with dilauroyl peroxide or azobis(isobutyronitrile) as initiator and proceed by a radical-chain mechanism that involves addition of the relatively electrophilic radical R1R2(EWG)C* to the styrene. This is followed by beta-scission of the derived alpha-tert-butoxybenzylic adduct radical to give But*, which then abstracts bromine from the organic halide to complete the chain. Alpha-1-adamantoxystyrene reacts similarly with R1R2C(Br)EWG, at higher temperature in refluxing octane using di-tert-amyl peroxide as initiator, and gives phenacylation products in generally higher yields than are obtained using alpha-tert-butoxystyrene. Simple iodoalkanes, which afford relatively nucleophilic alkyl radicals, can also be successfully phenacylated using alpha-1-adamantoxystyrene. O-Alkyl O-(tert-butyldimethylsilyl) ketene acetals H2C=C(OR)OTBS, in which R is a secondary or tertiary alkyl group, react in an analogous fashion with organic halides of the type R1R2C(Br)EWG to give the carboxymethylation products R1R2C(EWG)CH2CO2Me, after conversion of the first-formed silyl ester to the corresponding methyl ester. The silyl ketene acetals also undergo radical-chain reactions with electron-poor alkenes to bring about alkylation-carboxymethylation of the latter. For example, phenyl vinyl sulfone reacts with H2C=C(OBut)OTBS to afford ButCH2CH(SO2Ph)CH2CO2Me via an initial silyl ester. In a more complex chain reaction, involving rapid ring opening of the cyclopropyldimethylcarbinyl radical, the ketene acetal H2C=C(OCMe2C3H5-cyclo)OTBS reacts with two molecules of N-methyl- or N-phenyl-maleimide to bring about [3 + 2] annulation of one molecule of the maleimide, and then to link the bicyclic moiety thus formed to the second molecule of the maleimide via an alkylation-carboxymethylation reaction.

Carboncarbon bond formation by radical addition–fragmentation reactions of O-tert-alkyl enols and O-cyclopropylcarbinyl enols

Abstract Terminal alkenes of the type H2CC(OR1)X, in which R1 is a tertiary alkyl or a 1-cyclopropylethyl group and X=Ph, OSiMe2But, OEt or H, undergo radical-chain reactions with organic halides R2Hal to give carbonyl compounds R2CH2C(O)X.

Regioselectivity in the ring-opening β-scission of 2-phenyl-1,3-dioxan-2-yl radicals derived from bicyclic benzylidene acetals

The thiol-catalysed radical-chain redox rearrangement to benzoate esters of a number of cis- and trans-fused bicyclic benzylidene acetals derived from 1,3-diols has been investigated at ca. 130 °C in refluxing octane. The most generally effective and convenient combination of initiator and catalyst for this type of reaction consists of di-tert-butyl peroxide in conjunction with triisopropylsilanethiol. The benzoate esters are produced by β-scission of intermediate 2-phenyl-1,3-dioxan-2-yl radicals with fused cyclohexane or cyclopentane rings and there are two modes of cleavage for each radical, to give either a primary or a secondary 3-benzoyloxyalkyl radical. The regioselectivity of β-scission differs markedly depending on whether the ring junction is cis or trans, such that the trans-isomer gives preferentially the primary alkyl radical while the cis-isomer affords the secondary radical. Density functional calculations indicate that the β-scission proceeds through a product-like transition state in which the geometry at the emerging radical centre is quite close to planar. The regioselectivity observed in the β-scission of these bicyclic 1,3-dioxan-2-yl radicals can be understood in terms of the interplay between the thermodynamic driving force, charge-transfer stabilisation of the transition state and the degree of umbrella angle strain at the emerging radical centre.

Carbohydrate-derived thiols as protic polarity-reversal catalysts for enantioselective radical-chain reactions

A variety of novel homochiral carbohydrate-derived thiols, in which the SH group is attached to the anomeric carbon atom, have been prepared and characterised. These thiols have been evaluated as protic polarity-reversal catalysts to mediate the enantioselective radical-chain addition of triphenylsilane to the H2CCR1R2 group in prochiral methylenelactones to give chiral adducts of the general type Ph3SiCH2CHR1R2; chemical yields were uniformly high. Systematic changes in the structures of the thiols were made with the aim of increasing the enantioselectivity of hydrogen-atom abstraction from the SH group by the prochiral alkyl radical Ph3SiCH2ĊR1R2. Although adducts could be obtained in high enantiomeric excess in reactions carried out at 60 °C, no significant improvement in enantioselectivity could be achieved over that obtainable using simple tetra-O-acetyl-β-glucopyranose and -β-mannopyranose thiols as catalysts. It was found that the α-anomers of the pyranose thiols were ineffective at mediating enantioselective hydrogen-atom transfer to the radical Ph3SiCH2ĊR1R2. All the β-pyranose thiols gave asymmetric induction in the same sense, but two β-mannofuranose thiols with less polar substituents gave asymmetric induction in the opposite sense. It is concluded that both steric and dipole–dipole interactions between the prochiral carbon-centred radical and the thiol are important in determining enantioselectivity and that these interactions can act in opposition as well as co-operatively; solvent effects are also shown to be important.

Preparation of silanethiols by reaction of silanes with triphenylphosphine sulfide and with alkanethiols

Silanes react with triphenylphosphine sulfide by a radical-chain mechanism to give the corresponding silanethiols in good yield. Silanethiols are similarly formed when silanes react with tert-dodecanethiol. Enantiomerically pure (S)-ButMePhSiH gave racemic silanethiol with Ph3PS, but with tert-dodecanethiol silanethiol with an ee up to 60% has been obtained, although in low chemical yield.

Addition of silanethiols to aldehydes and ketones: a simple route to homochiral α-siloxyalkanethiols

Abstract In the presence of imidazole as a catalyst, silanethiols R 3 SiSH react by addition with aldehydes and with ketones that carry electron-withdrawing substituents to give α-siloxyalkanethiols R 1 R 2 C(SH)OSiR 3 . Diastereoselective addition of a silanethiol to an enantiopure aldehyde or ketone provides a convenient route to a homochiral α-siloxyalkanethiol R 1 R 2 C*(SH)OSiR 3 .