Trialkylsilyl Triflates Research Articles

Enantioselective, Catalytic Multicomponent Synthesis of Homoallylic Amines Enabled by Hydrogen-Bonding and Dispersive Interactions.

We report a one-step catalytic, enantioselective method for the preparation of homoallylic N-Boc amines directly from acetals. Reactive iminium ion intermediates are generated in situ through the combination of an acetal, a chiral thiourea catalyst, trialkylsilyl triflate, and N-Boc carbamate and are subsequently trapped by a variety of allylsilane nucleophiles. No homoallylic ether byproducts are detected, consistent with allylation of the iminium intermediate being highly favored over allylation of the intermediate oxocarbenium ion. Acetals derived from aromatic aldehydes possessing a variety of functional groups and substitution patterns yield homoallylic amines with excellent levels of enantiomeric enrichment. Experimental and computational data are consistent with an anchoring hydrogen-bond interaction between the protioiminium ion and the amide of the catalyst in the enantiodetermining transition state, and with stereodifferentiation achieved through specific noncovalent interactions (NCIs) with the catalyst pyrenyl moiety. Evidence is provided that the key NCI in the major pathway is a π-stacking interaction, contrasting with the cation-π interactions invoked in previously studied reactions promoted by the same family of aryl-pyrrolidino-H-bond-donor catalysts.

Nucleophilic Addition to Nitrones Using a Flow Microreactor

Nucleophilic addition reactions of soft carbon nucleophiles to nitrones in a flow microreactor are reported for the first time. Under microflow conditions at 30 to 0 °C, a range of nitrones can be efficiently transformed into the corresponding oxyiminium ions by reaction with either acyl halides or trialkylsilyl triflates. These can subsequently undergo the addition of nucleophiles including allyltributylstannane, ketene methyl tert-butyldimethylsilyl acetal, and N-silyl ketene imines to afford the corresponding adducts in high yields; such reactions at a similar temperature under batch conditions resulted in lower yields because of undesired side reactions.

Chemoselective Transformations of Aromatic Methoxymethyl Ethers Using Trialkylsilyl Triflate and 2,2'-Bipyridyl.

Aromatic methoxymethyl (MOM) ethers behave differently from aliphatic MOM ethers upon treatment with trialkylsilyl triflate (R3SiOTf) and 2,2′-bipyridyl. The aromatic MOM ethers are first converted to silyl ethers and subsequently deprotected by hydrolysis to give the mother alcohols when the R3SiOTf used is trimethylsilyl triflate (TMSOTf). Conversely, direct conversion of aromatic MOM ethers to aromatic triethylsilyl (TES) ethers is possible when the R3SiOTf used is triethylsilyl triflate (TESOTf).

Chemoselective Nucleophilic Functionalizations of Aromatic Aldehydes and Acetals via Pyridinium Salt Intermediates.

The development of a novel chemoselective functionalization can diversify the strategy for synthesizing the target molecules. The perfect chemoselectivity between aromatic and aliphatic aldehydes is difficult to achieve by the previous methods. The aromatic aldehyde-selective nucleophilic addition in the presence of aliphatic aldehydes was newly accomplished. Namely, the aromatic aldehyde-selective nucleophilic addition using arenes and allyl silanes proceeded in the presence of trialkylsilyl triflate and 2,2'-bipyridyl, while the aliphatic aldehydes completely remained unchanged. The reactive pyridinium-type salt intermediate derived from an aromatic aldehyde chemoselectively underwent the nucleophilic substitution. Moreover, the aromatic acetals as the protected aldehydes could be directly transformed into similar pyridinium salt intermediates, which reacted with various nucleophiles coexisting with the aliphatic aldehydes.

ChemInform Abstract: Preparation of Imidazolinium Salts by the Pd‐Catalyzed Reduction of Thioureas with Triethylsilane and Trialkylsilyl Triflate.

AbstractThe obtained imidazolium salts are precursors for NHCs.

Preparation of imidazolinium salts by the Pd-catalyzed reduction of thioureas with triethylsilane and trialkylsilyl triflate

A Pd-catalyzed method for the preparation of imidazolinium salts from the corresponding thioureas that could then be used for the synthesis of imidazolium and amidinium salts is described. This method has great potential because all the required reagents are readily available and thioureas are safely converted to their corresponding precursors of NHCs under mild conditions.

ChemInform Abstract: Catalytic Silicon‐Mediated Carbon—Carbon Bond‐Forming Reactions of Unactivated Amides.

In the presence of catalytic amounts of trialkylsilyl triflate and triethylamine, unactivated amides react with imines to afford the corresponding Mannich-type adducts in high yields with high anti selectivities. While silicon enolates have been widely used in organic synthesis for four decades, this is the first example of the catalytic use of the silicon species, to the best of our knowledge. Moreover, it is noteworthy that unactivated simple amides bearing α-protons that are less acidic than those of ketones and aldehydes can be successfully used in catalytic direct-type addition reactions. Finally, a preliminary trial of an asymmetric catalytic version was conducted and showed promising enantioselectivity of the desired product.

Catalytic Silicon-Mediated Carbon−Carbon Bond-Forming Reactions of Unactivated Amides

In the presence of catalytic amounts of trialkylsilyl triflate and triethylamine, unactivated amides react with imines to afford the corresponding Mannich-type adducts in high yields with high anti selectivities. While silicon enolates have been widely used in organic synthesis for four decades, this is the first example of the catalytic use of the silicon species, to the best of our knowledge. Moreover, it is noteworthy that unactivated simple amides bearing α-protons that are less acidic than those of ketones and aldehydes can be successfully used in catalytic direct-type addition reactions. Finally, a preliminary trial of an asymmetric catalytic version was conducted and showed promising enantioselectivity of the desired product.

ChemInform Abstract: Trialkylsilyl Triflate Promoted Conjugate Addition of Alkynylzinc Compounds to α,β-Enones.

ChemInform Abstract: Trialkylsilyl Triflate Promoted Conjugate Addition of Alkynylzinc Compounds to α,β-Enones.

H+, CH3+, and R3Si+ Carborane Reagents: When Triflates Fail

For decades, triflic acid, methyl triflate, and trialkylsilyl triflate reagents have served synthetic chemistry well as clean, strong electrophilic sources of H(+), CH(3)(+), and R(3)Si(+), respectively. However, a number of weakly basic substrates are unreactive toward these reagents. In addition, triflate anion can express undesired nucleophilicity toward electrophilically activated substrates. In this Account, we describe methods that replace triflate-based electrophilic reagents with carborane reagents. Using carborane anions of type CHB(11)R(5)X(6)(-) (R = H, Me, X; X = Br, Cl), members of a class of notably inert, weakly nucleophilic anions, significantly increases the electrophilicity of these reagents and shuts down subsequent nucleophilic chemistry of the anion. Thus, H(carborane) acids cleanly protonate benzene, phosphabenzene, C(60), etc., while triflic acid does not. Similarly, CH(3)(carborane) reagents can methylate substrates that are inert to boiling neat methyl triflate, including benzene, phosphabenzenes, phosphazenes, and the pentamethylhydrazinium ion, which forms the dipositive ethane analogue, Me(6)N(2)(2+). Methyl carboranes are also surprisingly effective in abstracting hydride from simple alkanes to give isolable carbocation salts, e.g., t-butyl cation. Trialkylsilyl carborane reagents, R(3)Si(carborane), abstract halides from substrates to produce cations of unprecedented reactivity. For example, fluoride is extracted from freons to form carbocations; chloride is extracted from IrCl(CO)(PPh(3))(2) to form a coordinatively unsaturated iridium cation that undergoes oxidative addition with chlorobenzene at room temperature; and silylation of cyclo-N(3)P(3)Cl(6) produces a catalyst for the polymerization of phosphazenes that functions at room temperature. Although currently too expensive for widespread use, carborane reagents are nevertheless of considerable interest as specialty reagents for making reactive cations and catalysts.

Thermodynamic Stability and Reactivity of Silylated Bis(oxy)iminium Ions

Silylation of various nitronates with trialkylsilyl triflates was investigated by applying NMR techniques. In several cases, a flexible nitronate-bis(oxy)iminium ion (as an ion pair with triflate as counterion) equlibrium was found, and its thermodynamic parameters were determined. Elevation of temperature or dilution shifts this equilibrium toward the reactants. Activation parameters for the C,C-coupling reaction of silylated bis(oxy)iminium ions with a series of reference nucleophiles were determined. Estimated electrophilicity of bis(oxy)iminium ions allows one to count on C,C-coupling when partner nucleophilicity is N > 4.

A selective Sc(OTf) 3-catalyzed trialkylsilyl ether to acetyl ester exchange reaction with β- l-idopyranoside and 3,4- O-isopropylidene-β- d-galactopyranoside derivatives

The selective silylation of monosaccharide building blocks is useful for preparing complex oligosaccharides. We now report that the diol, methyl (dimethylthexylsilyl 3- O-pivaloyl-β- l-idopyranosyl)uronate, can be selectively silylated at the O-2 position by trialkylsilyl triflates. After protection of O-4, the O-2 silyl group can be selectively replaced by acetate by taking advantage of a trialkylsilyl–acetate exchange reaction catalyzed by Sc(OTf) 3 in the presence of acetic anhydride. The high O-2 selectivity is shown for triethylsilyl (TES), tert-butyldimethylsilyl (TBS), and triisopropylsilyl (TIPS). The selective cleavage reaction only worked well for TES and TBS derivatives. A selection of silyl triflates and silyl chlorides were used as silylating reagents with ethyl 3,4- O-isopropylidene-1-thio-β- d-galactopyranoside. In most cases, silylation afforded 2,6-di- O-silylated products in high yields. Studies on the cleavage reaction showed that only the primary silylated protecting groups were replaced by acetyl groups. This reaction worked with a variety of silyl protecting groups but not the tert-butyldiphenylsilyl (TBDPS) protecting group. Unfortunately, the 1-thioethyl group was also sensitive to the Sc(OTf) 3, leading in these conditions to α/β mixtures of the 1-acetates, which compromised the synthetic utility of this reaction for these compounds. The sequence presented here is a useful synthetic route to differentially protected l-iduronic acid building blocks.

Trialkylsilyl Triflates — Practical Diastereoselective Catalysts in Conjugate Addition Reaction of Silyl Ketene Acetals and α,β‐Unsaturated Ketones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Studies on the synthesis of landomycin A: synthesis and glycosidation reactions of L-rhodinosyl acetate derivatives.

An efficient, eight-step synthesis of L-rhodinosyl acetate derivative 3 is described. The synthesis originates from methyl (S)-lactate and involves a highly stereoselective, chelate-controlled addition of allyltributylstannane to the lactaldehyde derivative 7. The beta-anomeric configuration of 3 was established with high selectivity by acetylation of the pyranose precursor with Ac(2)O and Et(3)N in CH(2)Cl(2). Preliminary studies of glycosidation reactions of 3 and L-rhodinosyl acetate 10 containing a 3-O-TES ether revealed that these compounds are highly reactive glycosidating agents and that trialkylsilyl triflates are effective glycosylation promoters. The best conditions for reactions with 15 as the acceptor involved use of diethyl ether as the reaction solvent and 0.2 equiv of TES-OTf at -78 degrees C. However, the TES ether protecting group of 10 proved to be too labile under these reaction conditions, and mixtures of 16a, 17, and 18a are obtained in reactions of 10 and 15. Disaccharide 17 arises via in situ cleavage of the TES ether of disaccharide 16a, while trisaccharide 18a results from a glycosidation of in situ generated 17 (or of 16a itself) with a second equivalent of 10. These problems were largely suppressed by using 3 with a 3-O-TBS ether protecting group as the glycosyl donor and 0.2 equiv of TES-OTf as the reaction promoter. Attempts to selectively glycosylate the C(3)-OH of diol acceptors 20 or 28 gave a 70:30 mixture of 21 and 22 in the reaction of 20 and a 43:27:30 mixture of regioisomeric trisaccharides 29 and 30 and tetrasaccharide 31 from the glycosidation reaction of 28. However, excellent results were obtained in the glycosidation of differentially protected disaccharide 34 using 1.5 equiv of 3 and 0.05 equiv of TBS-OTf in CH(2)Cl(2) at -78 degrees C. The latter step is an important transformation in the recently reported synthesis of the landomycin A hexasaccharide unit.

Silylation of silyl- and germylketenes containing bulky substituents at the silicon or germanium atom

Silylation of silyl- and germylketenes with trialkylsilyl triflates was studied. Either the corresponding bis-organoelement-substituted ketenes or mixtures of these compounds with isomeric (silyloxy)silylacetylenes were formed depending on the size of the substituents at the silicon or germanium atom (both in ketenes and triflates) and on the nature of the heteroelement. The resulting (silyloxy)silylacetylenes were isomerized into the corresponding bis-silylketenes upon prolonged storage.

Combination of Tris(pentafluorophenyl)borane and Trialkylsilyl Triflate as an Efficient Catalyst System for the Group Transfer Polymerization of Acrylates

Combination of Tris(pentafluorophenyl)borane and Trialkylsilyl Triflate as an Efficient Catalyst System for the Group Transfer Polymerization of Acrylates

Silyl Esters of Iminosulfenic Acids

Aminosulfines (thioamide S-oxides) were converted to silyl esters of iminosulfenic acids by treatment with trialkylsilyl triflates in the presence of triethylamine. Reaction of the title compounds with in situ prepared ketenes yields the corresponding new β-lactams having a silylsulfenate moiety at the 4-position of the ring.

Silyl Esters of Iminosulfenic Acids

Aminosulfines (thioamide S-oxides) were converted to silyl esters of iminosulfenic acids by treatment with trialkylsilyl triflates in the presence of triethylamine. Reaction of the title compounds with in situ prepared ketenes yields the corresponding new β-lactams having a silylsulfenate moiety at the 4-position of the ring.

Oxaferrocene Cryptands as Efficient Molecular Switches for Alkali and Alkaline Earth Metal Ions

The reactions of 3,4-diphenylcyclopent-2-en-1-one, cyclopent-2-en-1-one, 3,4-dimethylcyclopent-2-en-1-one, and 2,3,4,5-tetramethylcyclopent-2-en-1-one with various trialkylsilyl triflates (SiR3 = SiMe3, SiEt3, SiMe2tBu, SiiPr3) result in the formation of the respective cyclopentadienyl silyl ethers in virtually quantitative yields. The reactions of these cyclopentadienes with n-BuLi and FeCl2 give the respective substituted ferrocenyl trialkylsilyl ethers in 48−57% yields, which are synthetic equivalents of hydroxyferrocenes as generated by a suitable cleavage protocol: SiMe3-protected ferrocene alcohols (CH3CN + 10% H2O + Na2CO3); SiEt3 (CH3CN + 10% H2O + Na2CO3 + NaF); and SiMe2tBu protection (NBu4F·3H2O in CH3CN). Carrying out the deprotection in the presence of carbon electrophiles leads to the respective ferrocenyl alkyl ethers in excellent yields. Using 1-chloro-2-tosylethane results in 1,1‘-bis(2-chloroethoxy)-3,3‘,4,4‘-tetraphenylferrocene which was converted into 1,1‘-bis-(2-iodoethoxy)-3,3‘,4,4‘-tetraphenylferrocene in 89% yield, to be finally reacted with diaza-crown ethers (diaza-12-C-4, diaza-15-C-5, diaza-18-C-6). In this manner the respective ferrocene cryptands 23, 24, and 25 were generated as the 1 + 1 products in yields of 67−80%. The coordination of alkali and alkaline earth metal ions within the cavities of these ferrocene cryptands results in large anodic shifts of the redox potentials of the ferrocene units (23, E = +0.290 V; 23 + Ca2+, E = +0.670 V; 23 + Na+, E = +0.505 V; 24, E = +0.285 V; 24 + K+, E = +0.455 V) as determined by cyclic voltammetry. These anodic shifts are correlated with a decrease in the complex stability constant K of the respective metal ion complex (redox-switching effect) and in the case of 23 and Ca2+ amounts to a reduction of K by 3.4 × 106.

ChemInform Abstract: Trialkylsilyl Triflate Promoted Conjugate Addition of Alkynylcuprates to α,β‐Enones.

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