Diastereocontrol in open-chain nucleophilic attack on a double bond adjacent to a stereogenic centre carrying a silyl group

The bis[dimethyl(phenyl)silyl]cuprate reagent introduces a silyl group to the beta-position of three alpha,beta-unsaturated esters: methyl Z-4-dimethyl(phenyl)silylpent-2-enoate 11, and methyl Z- and E-(1'-dimethylphenylsilylbenzyl)but-2-enoates 14 and 15, diastereoselectively in the unexpected sense, syn to the silyl group in the conformation in which the hydrogen atom is 'inside'. The selectivity is low (58:42) in the first case 11, where the nucleophilic attack is adjacent to the stereogenic centre carrying the silyl group, and moderate (72:28) for both Z- and E-alpha,beta-unsaturated esters 14 and 15, where the nucleophilic attack is at the other end of the double bond from the stereogenic centre. It is conceivable that nucleophilic attack actually takes place in a conformation in which the donor substituent, the silicon-carbon bond, is out of conjugation with the double bond.     

Diastereoselective alkylation and reduction of β-alkoxyacylsilanes: stereoselective construction of three contiguous stereogenic centers

The nucleophilic addition reaction to acylsilanes, having stereogenic centers at the α and β positions, derived from the aldol reaction of dimethyl acetals and acylsilane silyl enol ethers gives the corresponding α-silylalcohols in high yields with excellent diastereoselectivity. The protiodesilylation of α-silylalcohols proceeds with complete retention of the configuration. In addition, the reduction of acylsilanes having stereogenic centers at the α and β positions affords the corresponding α-silylalcohols in good yields with high diastereoselectivity similarly to the nucleophilic addition. And the treatment of acylsilanes having a phenyl group on silicon atom with fluoride ion results in the formation of phenyl carbinol derivatives via migration of the phenyl group with high diastereoselectivity.     

Cyclooctanone synthesis via a formal [6+2] cycloaddition reaction of a dicobalt acetylene complex

An efficient formal [6+2] cycloaddition reaction of a new six-carbon unit with enol silyl ether was developed on the basis of a dicobalt hexacarbonyl propargyl cation species. Under the influence of EtAlCl₂, 6-benzoyloxy-2-(triisopropylsilyloxy)-1-hexen-4-yne-dicobalthexacarbonyl reacted with enol triisopropylsilyl ethers to yield 7-(triisopropylsilyloxy)-3-cyclooctyn-1-one-dicobalthexacarbonyl derivatives in good yield. The reactions with cyclic enol silyl ethers as well as acyclic enol silyl ethers exhibited remarkably high diastereoselectivity.     

Enol silyl ethers via copper(II)-catalyzed C-O bond formation

Copper(II) acetate catalyzes the coupling of pinacol vinylboronates with silanols producing enol silyl ethers. This represents a novel enol silyl ether synthesis via formation of the C-O bond instead of the conventional Si-O bond. This also constitutes the first transition-metal-catalyzed oxidative cross-coupling with silanols.     

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%.     

Metal nitrite: a powerful oxidizing reagent

An efficient and simple source of nitroso reagents and their oxidation reactions are described. The combination of a Lewis acid and a metal nitrite was applied to the oxidation of silyl enol ethers. Amino acid and peptide derivatives were easily accessed through in situ C-C bond cleavage of fully substituted silyl enol ethers upon oxidation.     

Ligand-induced control of C-H versus aliphatic C-C migration reactions of Rh carbenoids

The reaction of lithiated trimethylsilyldiazomethane (LTMSD) with aldehydes and subsequent quenching with TMSCl furnished relatively stable alpha-silylated diazocompounds. Upon treatment of the alpha-silylated diazocompounds with Rh2(OAc)4 in refluxing toluene, alpha-silyl silyl enol ethers were formed from unbranched and branched aliphatic aldehydes through predominantly 1,2-migration of the C-H bond. In contrast, treatment of the alpha-silylated diazocompounds with Rh2(tfa)4 at room temperature gave alpha-silyl silyl enol ethers through exclusive and unusual 1,2-migration of the C-C bond. The origin of the selectivity observed from the two catalysts is discussed in relation to early and late transition states.     

An approach to aliphatic 1,8-stereocontrol: diastereoselective syntheses of (±)-patulolide C and (±)-epipatulolide C

The tin(iv) bromide promoted reaction of 7-hydroxy-7-phenylhept-2-enyl(tributyl)stannane 11 with benzaldehyde gave a mixture of the epimeric 1,8-diphenyloct-3-ene-1,8-diols 12 and so indirect methods were developed for aliphatic 1,8-stereocontrol to complete diastereoselective syntheses of (±)-patulolide C 1 and (±)-epipatulolide C 40. (5Z)-3,7-syn-7-(2-Trimethylsilylethoxy)methoxyocta-1,5-dien-3-ol 17 was prepared from the tin(iv) chloride promoted reaction of 4-(2-trimethylsilylethoxy)methoxypent-2-enyl(tributyl)stannane 16 with acrolein (1,5-syn?:?1,5-anti = 96?:?4). An Ireland-Claisen rearrangement of the corresponding benzoyloxyacetate 21 with in situ esterification of the resulting acid using trimethylsilyldiazomethane gave methyl (4E,7Z)-2,9-anti-2-benzyloxy-9-(2-trimethylsilylethoxy)methoxydeca-4,7-dienoate 22 together with 10-15% of its 2,9-syn-epimer 26, the 2,9-syn-?:?2,9-anti-ratio depending on the conditions used. An 88?:?12 mixture of esters was taken through to the tert-butyldiphenylsilyl ether 38 of (±)-patulolide C 1 together with 6% of its epimer 39, by reduction, a Wittig homologation and deprotection/macrocyclisation. Following separation of the epimeric silyl ethers, deprotection of the major epimer 38 gave (±)-patulolide C 1. The success of 2,3-Wittig rearrangements of allyl ethers prepared from (5Z)-3,7-syn-7-(2-trimethylsilylethoxy)methoxyocta-1,5-dien-3-ol 17 was dependent on the substituents on the allyl ether. Best results were obtained using the pentadienyl ether 56 and the cinnamyl ether 49 that rearranged with >90?:?10 stereoselectivity in favour of (1E,5E,8Z)-3,10-syn-1-phenyl-10-(2-trimethylsilylethoxy)methoxyundeca-1,5,8-trien-3-ol 50. This product was taken through to the separable silyl ethers 38 and 39, ratio 7?:?93 by regioselective epoxidation and alkene reduction using diimide, followed by deoxygenation, ozonolysis, a Wittig homologation and selective deprotection/macrocyclisation. Deprotection of the major epimer 39 gave (±)-epipatulolide C 40.     

Acyclic stereoselection in the reaction of nucleophilic reagents with chiral N-acyliminium ions generated from N-

Optically active N-[1-(phenylsulfonyl)alkyl]imidazolidin-2-ones react at low temperature in the presence of tin tetrachloride to give acyclic N-acyliminium ions. These electrophilic substrates give addition products upon reaction with pi-nucleophiles. Allyltrimethylsilane affords the corresponding allylated products in good yields and high diastereoselectivity. The stereochemical outcome of this process can be rationalized by taking into account the preference of the intermediate N-acyliminium ion for an E configuration that favors the attack of the nucleophile from the si-si face. Disappointing results are obtained using silyl ketene acetals; conversely trimethylsilyl enol ether of acetophenone gives the corresponding adducts in high diastereoselectivity. The utilization of trimethylsilyl enol ether of 2-acetylfuran is particularly interesting since the corresponding adducts are obtained with good diastereoselectivity and the furan ring could be amenable of further synthetic transformations.     

Three-component reactions of sulfonylimidates, silyl glyoxylates and N-tert-butanesulfinyl aldimines: an efficient, diastereoselective, and enantioselective synthesis of Cyclic N-sulfonylamidines

Three-component coupling reactions of sulfonylimidates, silyl glyoxylates and N-tert-butanesulfinyl aldimines efficiently provide cyclic N-sulfonylamidines containing free endocyclic N-H. The formation of two C-C bonds (contiguous stereogenic carbons), one O-Si bond, and one C-N bond, together with the cleavage of the chiral auxiliary (tert-butanesulfinyl group), occurs with excellent chemoselectivity, diastereoselectivity, and enantioselectivity in this one-pot cascade transformation.     

Stereoselective synthesis of cycloheptanone derivatives via an intermolecular [5 + 2] cycloaddition reaction

[reaction: see text] A [5 + 2] cycloaddition reaction of a new five-carbon unit was developed on the basis of a dicobalt hexacarbonyl propargyl cation species. Under the influence of EtAlCl(2), [5-benzoyloxy-2-(triisopropylsiloxy)-1-penten-3-yne)]dicobalt hexacarbonyl reacted with enol triisopropylsilyl ethers to yield seven-membered dicobalt acetylene complexes in good yield. The reactions with cyclic enol silyl ethers as well as acyclic enol silyl ethers exhibited remarkably high diastereoselectivity. The cycloadducts can be easily converted into various kinds of cycloheptanone derivatives.     

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     

General route to 2,4,5-trisubstituted piperidines from enantiopure beta-amino esters. Total synthesis of pseudodistomin B triacetate and pseudodistomin F

The Michael addition reaction of enantiopure beta-amino esters with methyl acrylate followed by Dieckmann condensation and enol silylation affords the enol ethers 6, which are hydrogenated with catalysis by Raney-Ni at 80 atm and 80 degrees C to provide 2,4, 5-trisubstituted piperidines with high diastereoselectivity. In this case Ni-H attacks the C-C double bond from the direction of the 2-alkyl group to provide the products in which 2,4,5-trisubstrited groups are all cis to each other. While hydrogenation of enol ether 13 without a N-Boc protecting group gives the product 15 in which the 4-hydroxy group and 5-ester moiety are trans to the 2-alkyl group. By using the diastereoselective hydrogenation products 9d and 9e as key intermediates, pseudodistomin B triacetate and pseudodistomin F are synthesized. The key steps for these transformations include Curtius rearrangement and Julia olefination.     

alpha-Nitration of Ketones via Enol Silyl Ethers. Radical Cations as Reactive Intermediates in Thermal and Photochemical Processes

Highly colored (red) solutions of various enol silyl ethers and tetranitromethane (TNM) are readily bleached to afford good yields of alpha-nitro ketones in the dark at room temperature or below. Spectral analysis show the red colors to be associated with the intermolecular 1:1 electron donor-acceptor (EDA) complexes between the enol silyl ether and TNM. The formation of similar vividly colored EDA complexes with other electron acceptors (such as chloranil, tetracyanobenzene, tetracyanoquinodimethane, etc.) readily establish enol silyl ethers to be excellent electron donors. The deliberate irradiation of the diagnostic (red) charge-transfer absorption bands of the EDA complexes of enol silyl ethers and TNM at -40 degrees C affords directly the same alpha-nitro ketones, under conditions in which the thermal reaction is too slow to compete. A common pathway is discussed in which the electron transfer from the enol silyl ether (ESE) to TNM results in the radical ion triad [ESE(*)(+), NO(2)(*), C(NO(2))(3)(-)]. A subsequent fast homolytic coupling of the cation radical of the enol silyl ether with NO(2)(*)() leads to the alpha-nitro ketones. The use of time-resolved spectroscopy and the disparate behavior of the isomeric enol silyl ethers of alpha- and beta-tetralones as well as of 2-methylcyclohexanone strongly support cation radicals (ESE(*)(+)) as the critical intermediate in thermal and photoinduced electron-transfer as described in Schemes 1 and 2, respectively.     

The Use of tert-Butyl Vinyl Ether in Stepwise Electrophilic Addition Reactions

tert-Butyl vinyl ether (1) reacts with p-TolSCl to give 2-tert-butoxy-2-chloroethyl p-tolyl sulfide (2). In the presence of SnCl₄, 2 reacts with silyl enol ethers, allyltrimethylsilane, and vinyl ethers to form a C-C bond. In the case of vinyl ethers, the reaction proceeds through the formation of the 5-membered sulfonium salt intermediate which in turn can react with H₂O, TMSCN, allyltrimethylsilane, and Grignard reagents.     

Isomerization and Cleavage of Allyl Ethers of Carbohydrates by Trans- [Pd(NH3)2Cl2

Allyl ethers are widely used for the “temporary” protection of hydroxy groups in carbohydrates. The allyl group is conveniently removed by isomerization and subsequent cleavage of the labile prop-1-enyl group.² The rearrangement of allyl ethers to prop-1-enyl ethers is readily achieved by treatment with potassium t-butoxide in dimethyl sulfoxide, using tris(tripheny1phosphine)rhodium chloride, palladium on activated charcoal and by an ene reaction with diethylazodicarboxylate. acidic conditions, ozonolysis followed by alkaline hydrolysis, reaction with alkaline permanganate solution, or treatment with mercuric chloride in the presence of mercuric oxide. The isomerization of allyl ethers to prop-1-enyl ethers can also be carried out in the presence of palladium on carbon or complex bis(benzonitrile)palladium(11) chloride. Bruce and Roshan-Ali' showed that derivatives of allyl phenyl ether are smoothly cleaved by this complex. This has made it possible to remove the protecting group in a one-pot operation. We have now investigated the effect of palladium catalysts on the isomerization and cleavage of the allyl group in carbohydrate derivatives.     

Zirconium-mediated coupling reactions of amines and enol or allyl ethers: synthesis of allyl- and homoallylamines

An easy and efficient zirconium-mediated synthesis of allylamines from simple amines and enol ethers is described. This strategy also allows the synthesis of amino alcohol derivatives containing a Z double bond in their structure when 2,3-dihydrofuran is used. Simple conventional modification of these amino alcohols leads to 2-substituted piperidine derivatives. By applying this approach, a formal total synthesis of the alkaloid coniine is easily achieved from a protected butylamine. Finally, the zirconium-mediated reaction of amines and allyl phenyl ether furnishes homoallylamines or amino ethers depending on the structure of the starting amine.     

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.     

Rhodium-catalyzed α-fluoroalkylation reaction of ketones using silyl enol ethers

The treatment of silyl enol ethers with fluoroalkyl halides (R_f-X) in the presence of RhCl(PPh₃)₃ gave α-fluoroalkylated ketones. It seems that a rhodium complex derived from the silyl enol ether and RhCl(PPh₃)₃ played an important role for the oxidative addition of fluoroalkyl halides and the reductive elimination of the product.     

BINAP/AgOTf/KF/18-crown-6 as new bifunctional catalysts for asymmetric Sakurai-Hosomi allylation and Mukaiyama aldol reaction

A catalytic amount of KF.18-crown-6 complex is effective as a soluble fluoride source to activate an asymmetric Sakurai-Hosomi allylation with BINAP and silver(I) triflate catalyst. The allylation of a variety of aromatic, alpha,beta-unsaturated and aliphatic aldehydes with allylic trimethoxysilane resulted in high yields and remarkable enantioselectivities. In addition, the asymmetric Mukaiyama-type aldol reaction is achieved by using trimethoxysilyl enol ethers in the presence of the same catalysts. High anti selectivity is obtained from E-silyl enol ether, while Z-silyl enol ether gives syn selectivity.