Enol tosylates as viable partners in Pd-catalyzed cross-coupling reactions

[reaction: see text] Herein we demonstrate functionalized enol tosylates to be robust substrates that undergo Suzuki-Miyaura, Sonogashira, and Stille cross-coupling reactions to provide stereodefined trisubstituted unsaturated esters.     

Tetraorganoindates as nucleophilic coupling partners in Pd-catalyzed cross-coupling reactions

In situ-generated tetraorganoindate complexes from the reaction of 1 equiv of indium trichloride with 4 equiv of appropriate organometallics are efficient nucleophiles in Pd-catalyzed cross-coupling reactions. In this novel reaction tetraorganoindates containing methyl, 1 degree- and 2 degree-alkyl, vinyl, alkynyl, and aryl groups transfer the four organic groups to a variety of electrophiles with high atom efficiency. [reaction: see text]     

Palladium-catalyzed negishi cross-coupling reactions of unactivated alkyl iodides, bromides, chlorides, and tosylates

A single method (2% Pd(2)(dba)(3)/8% PCyp(3)/NMI in THF/NMP at 80 degrees C; Cyp = cyclopentyl) achieves the cross-coupling of a range of beta-hydrogen-containing primary alkyl iodides, bromides, chlorides, and tosylates with an array of alkyl-, alkenyl-, and arylzinc halides. The process is compatible with a variety of functional groups, including esters, amides, imides, nitriles, and heterocycles.     

Synthesis of enamines, enol ethers and related compounds by cross-coupling reactions

For several decades, enamines and related compounds have been used as intermediates in organic synthesis and many methods are known for their preparation. Most of the synthetic protocols, however, require harsh reaction conditions. Recently, a new approach has emerged, inspired by the analogous arylation of amines catalysed by palladium or copper complexes (Buchwald-Hartwig reaction). Simultaneous and independent work from several research groups has led to the development of very powerful protocols for the preparation of enamines and their derivatives that require only readily available starting materials and proceed under very mild reaction conditions. Noteworthy is the fact that in less than five years an almost unknown reaction has reached such a high level of scope and generality that it is now very frequently applied in total syntheses of natural products.     

Nickel-catalyzed cross-coupling reactions of benzylic zinc reagents with aromatic bromides, chlorides and tosylates

Benzylic zinc reagents prepared by direct insertion of zinc to benzylic chlorides in the presence of LiCl undergo smooth cross-coupling reactions with aromatic chlorides, bromides and tosylates using Ni(acac)(2) and PPh(3) as a catalyst system.     

Functionalised butanediacetal-protected 1,2-diols as suitable partners for Pd-catalysed cross-coupling reactions

A new method for the synthesis of dienes and enynes containing chiral 1,2-diols is described. The strategy is based on the Pd-catalysed cross-coupling reactions of a series of vinyl and alkynyl asymmetric butanediacetal-protected building blocks. After the coupling, removal of the protecting group leads to the desired functionalised dienes and enynes.     

Unexpected intermolecular pd-catalyzed cross-coupling reaction employing heteroaromatic carboxylic acids as coupling partners

Aryl-substituted five-membered heteroaromatics have attracted great interest over the past years due to their presence in a large number of pharmaceuticals and natural products. Recently, an advance in the preparation of these scaffolds was achieved by employing a C-H functionalization strategy. This method allows easy access to these biaryl motifs by precluding the necessity of preparing specific coupling partners, although poor regioselectivity is sometimes observed when more than one reactive C-H is present on the substrate. In an effort to circumvent this liability, we envisioned the use of a carboxylic acid moiety as a blocking group that could be later functionalized or removed. Remarkably, the coupling was found to occur exclusively at the position previously occupied by the acid, even in the presence of a reactive C-H group. This selective transformation was also found to proceed with other heteroaromatic carboxylic acids, allowing for the preparation of a variety of aryl-substituted heteroaromatics that would be difficult to obtain via other methods.     

Two-step, one-pot Ni-catalyzed neopentylglycolborylation and complementary Pd/Ni-catalyzed cross-coupling with aryl halides, mesylates, and tosylates

Two-step, one-pot neopentylglycolborylation of aryl iodides and bromides catalyzed by NiCl2(dppe) and NiCl2(dppp) is reported. Electron-rich and electron-deficient aryl neopentylglycolboronates were efficiently cross-coupled with aryl iodides, bromides, chlorides, mesylates, and tosylates by exploiting complementary Pd/Ni and Ni/Ni catalysis. The borylation route was further extended to a three-step, one-pot synthesis of biaryls via in situ Ni-catalyzed borylation and Pd-mediated cross-coupling.     

Selective iron-catalyzed cross-coupling reactions of grignard reagents with enol triflates, acid chlorides, and dichloroarenes

Cheap, readily available, air stable, nontoxic, and environmentally benign iron salts such as Fe(acac)(3) are excellent precatalysts for the cross-coupling of Grignard reagents with alkenyl triflates and acid chlorides. Moreover, it is shown that dichloroarene and -heteroarene derivatives as the substrates can be selectively monoalkylated by this method. All cross-coupling reactions proceed very rapidly under notably mild conditions and turned out to be compatible with a variety of functional groups in both reaction partners. A detailed analysis of the preparative results suggests that iron-catalyzed C-C bond formations can occur via different pathways. Thus, it is likely that reactions of methylmagnesium halides involve iron-ate complexes as the active components, whereas reactions of Grignard reagents with two or more carbon atoms are effected by highly reduced iron-clusters of the formal composition [Fe(MgX)(2)](n) generated in situ. Control experiments using the ate-complex [Me(4)Fe]Li(2) corroborate this interpretation.     

Copper-catalyzed cross-coupling of nonactivated secondary alkyl halides and tosylates with secondary alkyl Grignard reagents

Practical catalytic cross-coupling of secondary alkyl electrophiles with secondary alkyl nucleophiles under Cu catalysis has been realized. The use of TMEDA and LiOMe is critical for the success of the reaction. This cross-coupling reaction occurs via an S(N)2 mechanism with inversion of configuration and therefore provides a general approach for the stereocontrolled formation of C-C bonds between two tertiary carbons from chiral secondary alcohols.     

Chemoselective and scalable preparation of alkyl tosylates under solvent-free conditions

The improved method for the efficient tosylation of alcohols has been reported using two procedures (A and B). Procedure A: methanol, ethanol, benzyl alcohols, and valuable ethylene glycols can be converted into their corresponding alkyl tosylates in very fast, simple, and efficient grinding method using potassium carbonate as solid base. Other primary and secondary alcohols need to add potassium hydroxide to reaction mixture (procedure B). High selectivity of tosylation was observed for these two procedures. Scale up ability was found in this method even in 100 mmol of substrate. The present method is the example of solid-state tosylation using tosyl chloride, and is a green chemical process due to solvent-free conditions.     

Copper-catalyzed cross-coupling of functionalized alkyl halides and tosylates with secondary and tertiary alkyl grignard reagents

Added value: A copper-based method is highly efficient for the cross-coupling of alkyl electrophiles with secondary and tertiary alkyl Grignard reagents. The method is distinguished by its broad substrate scope and high functional group tolerance.     

Silazanes/catalytic bases: mild,powerful and chemoselective agents for the preparation of enol silyl ethers from ketones and aldehydes

We have developed an efficient method for the preparation of enol silyl ethers using novel agents, silazanes together with NaH or DBU catalyst, wherein TMS and TBDMS groups were smoothly and chemoselectively introduced into ketones and aldehydes under mild conditions.     

Synthesis of substituted pyrazoles via tandem cross-coupling/electrocyclization of enol triflates and diazoacetates

The synthesis of 3,4,5-trisubstituted pyrazoles via a tandem catalytic cross-coupling/electrocyclization of enol triflates and diazoacetates is presented. The initial scope of this methodology is demonstrated on a range of differentially substituted acyclic and cyclic enol triflates as well as an elaborated set of diazoacetates to provide the corresponding pyrazoles with a high degree of structural complexity.     

Divergent preparation of allenyl tosylates and α-tosyloxy ketones by facile and efficient isomerization of CF3-containing propargylic tosylates

Treatment of trifluoromethylated propargylic tosylates with hydroxides in a water-organic biphasic solvent system efficiently led to isomerization to allenyl tosylates or hydration to α-tosyloxy ketones at room temperature, just by selection of appropriate reaction conditions.     

Stereoselective enol tosylation: preparation of trisubstituted alpha,beta-unsaturated esters

[Reaction: see text] The stereoselective preparation of (E)- or (Z)-trisubstituted alpha,beta-unsaturated esters in three steps from N-protected glycine is presented. The key step in the synthesis is the highly selective enol tosylation of gamma-amino beta-keto esters. The enol tosylates are stable, crystalline compounds that undergo smooth and effective Suzuki-Miyaura coupling reaction with a variety of aryl boronic acids.     

Chiral alpha,beta-dialkoxy- and alpha-alkoxy-beta-aminostannanes: preparation and copper-mediated cross-coupling

Addition of Zn(n-Bu(3)Sn)(2) to prochiral aldehydes affords anti-alpha,beta-dialkoxy- and anti-alpha-alkoxy-beta-aminostannanes in good yield (up to 77%) and excellent diastereoselectivity (up to 98% de). syn-Isomers are accessed from the initial adducts via Mitsunobu inversion/saponification. The corresponding thionocarbamates undergo mild Cu(I)-mediated cross-coupling with a variety of organic halides, inter alia, allylic, cinnamylic, propargylic, and acetylenic, with retention of configuration. [reaction: see text]     

Ruthenium-catalyzed vinylsilane synthesis and cross-coupling as a selective approach to alkenes: benzyldimethylsilyl as a robust vinylmetal functionality

[reaction: see text] Ruthenium-catalyzed alkyne hydrosilylation or silyl-alkyne Alder ene reactions provide entry into benzyldimethylsilyl (BDMS)-substituted alkenes. The BDMS-vinylsilanes are further elaborated through mild palladium-catalyzed cross coupling and show significant stability to intervening synthetic operations, including silyl ether deprotection.