Mechanism of Mukaiyama-Michael Reaction of Ketene Silyl Acetal: Electron Transfer or Nucleophilic Addition?

Mechanism of Mukaiyama-Michael reaction of ketene silyl acetal has been discussed. The competition reaction employing various types of ketene silyl acetals reveals that those bearing more substituents at the beta-position react preferentially over less substituted ones. However, when ketene silyl acetals involve bulky siloxy and/or alkoxy group(s), less substituted compounds react preferentially. The Lewis acids play an important role in these reactions. Enhanced preference for the more sterically demanding Michael adducts is obtained with Bu(2)Sn(OTf)(2), SnCl(4), and Et(3)SiClO(4) in the former reaction while TiCl(4) gives the highest selectivity for the less sterically demanding products in the latter case. These results are interpreted in terms of alternative reaction mechanisms. The reaction of less bulky ketene silyl acetals are initiated by electron transfer from these compounds to a Lewis acid. On the other hand, bulkier ketene silyl acetals undergo a ubiquitous nucleophilic reaction. Such a mechanistic change is discussed based on a variety of experimental results as well as the semiempirical PM3 MO calculations.     

Crucial role of the ligand of silyl Lewis acid in the Mukaiyama aldol reaction

The Me3SiX-induced Mukaiyama aldol reaction proceeds through each catalytic cycle under the influence of X-: the silyl group of Me3SiNTf2 does not release from -NTf2 and that of silyl enol ether intermolecularly transfers to the product, while the silyl group of Me3SiOTf remains in the product and that of the silyl enol ether becomes the catalyst for the next catalytic cycle.     

Comparison between electron transfer and nucleophilic reactivities of ketene silyl acetals with cationic electrophiles

The products and kinetics for the reactions of ketone silyl acetals with a series of p-methoxy-substituted trityl cations have been examined, and they are compared with those of outer-sphere electron transfer reactions from 10,10'-dimethyl-9,9', 10, 10'- tetrahydro-9,9'-biacridine [(AcrH)2] to the same series of trityl cations as well as other electron acceptors. The C-C bond formation in the reaction of beta,beta-dimethyl-substituted ketene silyl acetal (1: (Me2C=C(OMe)OSiMe3) with trityl cation salt (Ph3C+ClO4-) takes place between 1 and the carbon of para-positon of phenyl group of Ph3C+, whereas a much less sterically hindered ketene silyl acetal (3: H2C=C(OEt)OSiEt3) reacts with Ph3C+ at the central carbon of Ph3C+. The kinetic comparison indicates that the nucleophilic reactivities of ketene silyl acetals are well correlated with the electron transfer reactivities provided that the steric demand at the reaction center for the C-C bond formation remains constant.     

Synthetic Studies on and Mechanistic Insight into [W(CO)5(L)]‐Catalyzed Stereoselective Construction of Functionalized Bicyclo[5.3.0]decane Frameworks

Stereoselective preparation of a variety of synthetically useful functionalized bicyclo[5.3.0]decane derivatives was achieved by tandem cyclization of 3‐siloxy‐1,3,9‐triene‐7‐yne derivatives based on the electrophilic activation of alkynes catalyzed by [W(CO)₅(L)]. The reaction proceeded smoothly under photoirradiation, and various substrates were cyclized to give the corresponding bicyclic compounds with up to four chiral centers stereospecifically. Reactions of siloxydienes with a silyl substituent as an equivalent of a hydroxyl group also proceeded with wide generality to afford silyl‐substituted bicyclo[5.3.0]decanes, which were highly useful as synthetic intermediates. Stereochemical studies concerning the silyl enol ether moiety suggested that two types of reaction pathway for the formation of seven‐membered rings were present. The reaction of (Z)‐enol silyl ethers proceeded through Cope rearrangement of cis‐divinylcyclopropane intermediates, and that of (E)‐enol silyl ethers by 1,4‐addition of the dienyl tungsten species at the position δ to the metal atom. In the reactions of siloxydiene derivatives with silyl substituents, all possible diastereomers could be synthesized stereoselectively by changing the geometry of the silyl enol ether and enyne moieties.     

Oxidative C-C bond-forming reaction of electron-rich alkylbenzyl ether with trimethylvinyloxysilane

Treatment of an electron-rich benzyl ether with DDQ at ambient temperature followed by addition of a silyl enol ether undergoes a C-C bond-forming reaction to afford 3-alkoxy-3-phenyl-propionyl compound. This is a general reaction and works well with a variety of silyl enol ethers to give carbonyl products in yields ranging from 10 to 85%.     

Silyl enol ethers as protective groups for alkyl 4-halo-3-oxobutanoates in the Arbuzov reaction with triethyl phosphite

Alkyl 4-bromo- and 4-chloro-3-oxobutanoates were protected as silyl enol ethers. The Arbuzov reaction of these new compounds with triethyl phosphite gave the corresponding silyl enol phosphonates in high yield. Facile deprotection of the silyl group with water gave alkyl 4-(diethoxyphosphinyl)-3-oxobutanoates in high yields. Protection of 1-methylethyl 4-bromo-3-oxobutanoate as the enol acetate followed by the subsequent reaction with triethyl phosphite gave the corresponding phosphonate in high yield. Deprotection with potassium 2-propoxide gave 1-methylethyl 4-(diethoxyphosphinyl)-3-oxobutanoate in good yield. © 1997 John Wiley & Sons, Inc.     

A Theoretical and Experimental Study of the Effects of Silyl Substituents in Enantioselective Reactions Catalyzed by Diphenylprolinol Silyl Ether

The effect of silyl substituents in diphenylprolinol silyl ether catalysts was investigated. Mechanistically, reactions catalyzed by diphenylprolinol silyl ether can be categorized into three types: two that involve an iminium ion intermediate, such as for the Michael‐type reaction (type A) and the cycloaddition reaction (type B), and one that proceeds via an enamine intermediate (type C). In the Michael‐type reaction via iminium ions (type A), excellent enantioselectivity is realized when the catalyst with a bulky silyl moiety is employed, in which efficient shielding of a diastereotopic face of the iminium ion is directed by the bulky silyl moiety. In the cycloaddition reaction of iminium ions (type B) and reactions via enamines (type C), excellent enantioselectivity is obtained even when the silyl group is less bulky and, in this case, too much bulk reduces the reaction rate. In other cases, the yield increases when diphenylprolinol silyl ethers with bulky substituents are employed, presumably by suppressing side reactions between the nucleophilic catalyst and the reagent. The conformational behaviors of the iminium and enamine species have been determined by theoretical calculations. These data explain the effect of the bulkiness of the silyl substituent on the enantioselectivity and reactivity of the catalysts.     

Effect of the "supersilyl" group on the reactivities of allylsilanes and silyl enol ethers

Kinetics of the reactions of allylsilanes (1) and silyl enol ethers (2) with benzhydrylium ions (3) were studied by UV-vis spectroscopy in dichloromethane at 20 °C. The less than three times higher reaction rates of the tris(trimethylsilyl)silyl compounds in comparison to the corresponding trimethylsilyl compounds indicate that the previously reported strong electron-donating effect of the supersilyl group operates only in the α-position and not in the β-position.     

Concise Synthesis of Multisubstituted Isoquinolines from Pyridines by Regioselective Diels–Alder Reactions of 2‐Silyl‐3,4‐pyridynes

A four‐step regioselective synthesis of multisubstituted isoquinoline derivatives from 3‐bromopyridines was developed by the Diels–Alder (DA) reactions of 2‐silyl‐3,4‐pyridynes with furans, followed by functional‐group transformations. In particular, the silyl group at the C2‐position of the 3,4‐pyridynes played two important roles: firstly, it functioned as the directing group for the DA reaction, and secondly, it served to introduce diverse substituents at the C1‐position of the isoquinolines by electrophilic ipso‐substitution.     

Investigations on a novel silyl transfer reaction in heterodimetallic chemistry

Heterodinuclear silyl complexes of the type [(OC)3(R3Si)[Fe(mu-PPh2)Pt](CO)(PPh3)], which contain a [Fe(mu-P)Pt] triangular core, were previously reported to undergo an unprecedented dyotropic-type rearrangement involving migration of the silyl group from iron to platinum with concomitant 1,2 migration of CO from Pt to Fe. In the resulting complexes of formula [(OC)4[Fe(mu-PPh2)Pt](SiR3)(PPh3)], the Si atom occupies a cis position at the planar Pt center with respect to the phosphido bridge. DFT calculations were employed to elucidate the mechanism of this intramolecular silyl migration reaction. When the Fe-Pt precursor complex is [(OC)3(R3Si)[Fe(mu-PPh2)Pt](PPh3)2], the reaction sequence involves (i) the substitution of PPh3 by CO at Pt, (ii) the concerted migration of CO and SiR3, and (iii) the cis-trans isomerization at Pt. The calculations support the exergonic character of the overall process. An explanation for the experimental observation of only one product isomer being formed is possible via frontier molecular orbital analysis. Consistent with the experimental findings, the transition states of the migration (a species with a triply bridged intermetallic bond) and isomerization steps were found to be energetically within reach at room temperature. Additional support for the suggested mechanism also comes from the fact that relative silyl migration activities could be rationalized by the means of quantum chemistry.     

Synthesis and cross-coupling reaction of alkenyl[(2-hydroxymethyl)phenyl]dimethylsilanes

Highly stable alkenyl[2-(hydroxymethyl)phenyl]dimethylsilanes are prepared by stereo- and regioselective hydrosilylation of alkynes catalyzed either by a platinum or ruthenium catalyst using protected [2-(hydroxymethyl)phenyl]dimethylsilanes. Cyclic silyl ether, 1,1-dimethyl-2-oxa-1-silaindan, also serves as a starting material for the alkenylsilanes by the ring-opening reaction with alkenyl Grignard reagents. The resulting alkenylsilanes undergo cross-coupling reaction with various aryl and alkenyl iodides under reaction conditions employing K₂CO₃ as a base at 35–50 °C in highly regio- and stereospecific manners. The reaction tolerates a diverse range of functional groups including silyl protections. The silicon residue is readily recovered and reused on a gram-scale synthesis. Intramolecular coordination of a proximal hydroxyl group is considered to efficiently form pentacoordinate silicates having a transferable group possibly at an axial position and, thus, responsible for the cross-coupling reaction under conditions significantly milder than those reported for the silicon-based reactions.     

Quenching of metal‐catalyzed living radical polymerization with silyl enol ethers

Various silyl enol ethers were employed as quenchers for the living radical polymerization of methyl methacrylate with the R Cl/RuCl₂(PPh₃)₃/Al(Oi–Pr)₃ initiating system. The most effective quencher was a silyl enol ether with an electron‐donating phenyl group conjugated with its double bond [CH₂C(OSiMe₃)(4‐MeOPh) ( 2a )] that afforded a halogen‐free polymer with a ketone terminal at a high end functionality [F̄_n ∼ 1]. Such silyl compounds reacted with the growing radical generated from the dormant chloride terminal and the ruthenium complex to give the ketone terminal via the release of the silyl group along with the chlorine that originated from the dormant terminal. In contrast, less conjugated silyl enol ethers such as CH₂C(OSiMe₃)Me were less effective in quenching the polymerization. The reactivity of the silyl compounds to the poly(methyl methacrylate) radical can be explained by the reactivity of their double bonds, namely, the monomer reactivity ratios of their model vinyl monomers without the silyloxyl groups. The lifetime of the living polymer terminal was also estimated by the quenching reaction mediated with 2a . © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4735–4748, 2000     

Reaction of tertiary cyclopropyl silyl ethers with diethylaminosulfur trifluoride: the effects of substituents on the cleavage of the cyclopropane ring

The reaction of tertiary cyclopropanol silyl ethers with diethylaminosulfur trifluoride usually causes ring opening to produce allylic fluorides. However, cyclopropyl silyl ethers bearing a strong electron-donating substituent at C1 or an electron-withdrawing substituent at C2 do not afford allylic fluorides but fluorocyclopropanes. It has also been proved that an electron-donating substituent at C2 of the tertiary cyclopropanol silyl ethers promotes ring opening in the reaction with diethylaminosulfur trifluoride.     

New approaches toward the synthesis of (D-homo) steroid skeletons using Mukaiyama reactions

New, short, and flexible procedures have been developed for syntheses of steroid and D-homo steroid skeletons. A Mukaiyama reaction between the silyl enol ether of 6-methoxytetralone and 2-methyl-2-cyclopentenone or carvone, with transfer of the silyl group to the receiving enone, gave a second silyl enol ether. Addition of a carbocation, generated under Lewis acid conditions from 3-methoxy-2-butenol, 3-ethoxy-3-phenyl-2-propenol or 3-methoxy-2-propenol to this second silyl enol ether gave adducts, which could not be cyclized by aldol condensation to (D-homo) steroid skeletons. The Mukaiyama-Michael reaction of the silyl enol ether of 6-methoxy tetralone with 2-methyl-2-cylopentenone gave a second silyl enol ether, which reacted in high yield with a carbocation generated from 3-hydroxy-3-(4-methoxyphenyl)propene. Ozonolysis of the double bond in this adduct gave a tricarbonyl compound (Zieglers triketone), which has been used before in the synthesis of 9,11-dehydroestrone methyl ether. A second synthesis of C17 substituted CD-trans coupled (D-homo) steroid skeletons has been developed via addition of a carbocation, generated with ZnBr₂ from a Torgov reagent, to a silyl enol ether containing ring D precursor. The obtained seco steroids have been cyclized under formation of the 8-14 bond by treatment with acid. The double bonds in one of the cyclized products have been reduced to a C17-substituted all trans steroid skeleton.     

Synthesis of 1-hydrocarbon substituted cyclopropyl silyl ketones

The synthesis of cyclopropyl silyl ketones possessing a hydrocarbon group at 1-position of three-membered ring was investigated. The reaction of sulfoxonium ylide with α,β-unsaturated acylsilanes derived from α,β-unsaturated aldehydes did not afford the desired acylsilane derivatives. Instead, the corresponding silyl enol ethers were yielded exclusively. On the other hand, the Corey-Chaykovsky cyclopropanation of α-substituted α,β-unsaturated aldehydes proceeded well to give 1-substituted cyclopropyl aldehydes. The silyl substitution of formyl proton in the obtained aldehydes via umpolung of carbonyl group afforded the target acylsilanes.     

Super silyl group for a sequential diastereoselective aldol-polyhalomethyllithium addition reaction

The super silyl group governs high diastereoselectivity and yields for a sequential aldol-polyhalomethyllithium addition reaction. This unique silyl group is necessary to obtain the diastereoselectivities associated with this sequential reaction, capable of generating two new stereocenters. Alpha-polyhalomethylcarbinols are generated with the simple and inexpensive dihalomethanes and trihalomethanes.     

Direct transformation of silyl enol ethers into functionalized allenes

The first elimination reactions of silyl enol ethers to lithiated allenes are reported. These reactions allow a direct transformation of readily available silyl enol ethers into functionalized allenes. The action of three to four equivalents of lithium diisopropylamide (LDA) on silyl enol ethers results in the formation of lithiated allenes by initial allylic lithiation, subsequent elimination of a lithium silanolate, and finally, lithiation of the allene thus formed. Starting with amide-derived silyl imino ethers, lithiated ketenimines are obtained. A variety of reactions of the lithiated allenes with electrophiles (chlorosilanes, trimethylchlorostannane, dimethyl sulfate and ethanol) were carried out. Elimination of silanolate is observed only for substrates that contain the hindered SiMe2tBu or Si(iPr)3 moiety, but not for the SiMe3 group. The reaction of 1,1-dilithio-3,3-diphenylallene with ketones provides a convenient access to novel 1,1-di(hydroxymethyl)allenes which undergo a domino Nazarov-Friedel-Crafts reaction upon treatment with p-toluenesulfonic acid.     

Palladium-catalyzed silyl C(sp3)-H bond activation

The first transition-metal-catalyzed activation of silyl C(sp(3))-H bond was realized and synthetically applied. A variety of organic skeletons substituted with SiMe(3) groups could undergo the Pd-catalyzed intramolecular coupling reaction, resulting in an unprecedented synthetic method for yielding six-membered silacycles. It was found that the adjacent Si atom played an essential role for the activation of the C(sp(3))-H bond of the SiMe(3) group; no activation reaction of the C(sp(3))-H bond of the CMe(3) group took place under the same reaction conditions.     

Highly selective γ-alkylation of triisopropylsilylallyl anion. Synthesis of α-triisopropylsilyl aldehydes.

The reaction of triisopropylsilylallyllithium with alkyl halides took place with considerably greater γ-selectivity than reported for trimethylsilyl allyllithium. Silica gel induced rearrangement of the epoxides 5 derived from the alkylation products 3 gave α-triisopropylsilyl aldehydes 6 by a process in which silyl group transposition occurred with predominant inversion at the migration terminus.     

Studies into the Diels-Alder reactions of 5-trimethylsilylthebaine

The introduction of a 5-trimethylsilyl group on the least hindered face of the diene thebaine was anticipated to favor attack by dienophiles from the alternate face, but only gave rise to a rearrangement product when treated with 3-butene-2-one at 110 °C. Reaction with the more reactive benzoquinone at lower temperature gave rise to a very slow reaction from the same face as the silyl group, indicating that a trimethylsilyl group does not sufficiently hinder this face to achieve reaction at the other face.