20218-41-1

Upstream product

• 501-65-5 diphenyl acetylene 
• 67-56-1 methanol 
• 64-17-5 ethanol 
• 584-02-1 2-pentanol 
• 121700-16-1 1,1-dichloro-2-phenyl-1-butene 
• 106-93-4 ethylene dibromide 
• 67-63-0 isopropyl alcohol 
• 622-76-4 1-phenyl-1-butyne 
• 591-51-5 phenyllithium 
• 557-20-0 diethylzinc 
• 97-93-8 triethylaluminum 
• 1007-32-5 benzyl ethyl ketone 
• 100-59-4 phenylmagnesium chloride 
• 252975-34-1 selenophosphoric acid Se-(1-benzoyl-1-phenylpropyl) ester O,O-diethyl ester 

Downstream Products

• 10540-29-1 tamoxifen 

Relevant academic research and scientific papers

Stereoconvergent and -divergent synthesis of tetrasubstituted alkenes by nickel-catalyzed cross-couplings

We report the development of a method to diastereoselectively access tetrasubstituted alkenes via nickel-catalyzed Suzuki-Miyaura cross-couplings of enol tosylates and boronic acid esters. Either diastereomeric product was selectively accessed from a mixture of enol tosylate starting material diastereomers in a convergent reaction by judicious choice of the ligand and reaction conditions. A similar protocol also enabled a divergent synthesis of each product isomer from diastereomerically pure enol tosylates. Notably, high-throughput optimization of the monophosphine ligands was guided by chemical space analysis of the kraken library to ensure a diverse selection of ligands was examined. Stereoelectronic analysis of the results provided insight into the requirements for reactive and selective ligands in this transformation. The synthetic utility of the optimized catalytic system was then probed in the stereoselective synthesis of various tetrasubstituted alkenes, with yields up to 94% and diastereomeric ratios up to 99:1 Z/E and 93:7 E/Z observed. Moreover, a detailed computational analysis and experimental mechanistic studies provided key insights into the nature of the underlying isomerization process impacting selectivity in the cross-coupling.

Regioselective Synthesis of α-Functional Stilbenes via Precise Control of Rapid cis- trans Isomerization in Flow

The rapid cis-trans isomerization of α-anionic stilbene was regioselectively controlled by using flow microreactors, and its reaction with various electrophiles was conducted. The reaction time was precisely controlled within milliseconds to seconds at -50 °C to selectively give the cis- or trans-isomer in high yields. This synthetic method in flow was well-applied to synthesize precursors of commercial drug compound, (E)- and (Z)-tamoxifen with high regioselectivity and productivity.

Geometry-Constrained Iminopyridyl Palladium-Catalyzed Hydroarylation of Alkynes to Prepare Tri-substituted Alkenes Using Alcohol as Reductant

We developed an efficient and straightforward method to prepare tri-substituted alkenes through palladium-catalyzed hydroarylation of alkynes with aryl bromides. Diarylacetylenes and alkyl(aryl)acetylenes could be well hydroarylated with various aryl bromides in moderate to excellent yields. Mechanistic studies suggested that alcohol was the reductant to provide hydride through β-H elimination. Gram scale reaction further demonstrated the practicality and efficiency of the newly developed strategy. (Figure presented.).

Palladium-Catalyzed C?H Alkenylation of Arenes with Alkynes: Stereoselective Synthesis of Vinyl Chlorides via a 1,4-Chlorine Migration

A directing group-free, ligand-promoted palladium-catalyzed C?H arylation of internal alkynes with simple arenes was developed. Alkenyl chlorides resulting from a 1,4-chlorine migration or trisubstituted alkenes were produced in moderate to good yields depending on the type of alkyne.

Pd(OAc)2-Catalyzed Desulfinative Cross-Coupling of Sodium Sulfinates with β-Bromostyrenes: Synthesis of Tamoxifen

A Pd(OAc)2-catalyzed desulfinative cross-coupling of (Z)-β-halostyrenes with sodium sulfinates in the presence of PPh3 and Na2CO3 at reflux in good yields is reported. The stereocontrolled cross-coupling process provides a series of sulfonylmethyl (Z)-stilbenes. A synthesis of tamoxifen was studied.

Versatile Relay and Cooperative Palladium(0) N-Heterocyclic Carbene/Copper(I) N-Heterocyclic Carbene Catalysis for the Synthesis of Tri- and Tetrasubstituted Alkenes

Two new and efficient dual catalytic procedures for the synthesis of tri- and tetrasubstituted alkenes using aryl bromides and chlorides are reported. The formation of these vinyl arenes occurs independently in a one-pot relay and a one-pot cooperative procedure using well-defined Pd and Cu N-heterocyclic carbene (NHC) complexes. Mechanistic studies were performed to elucidate the key role of the solvent in each procedure as well as the formation of the key intermediate, [Cu(alkenylboron)(NHC)], which allows transmetalation with the Pd-NHC co-catalyst in the cooperative catalysis.

One-pot multistep synthesis of trisubstituted alkenes from N -tosylhydrazones and alcohols

A one-pot procedure for the synthesis of trisubstituted alkenes from N-tosylhydrazones and alcohols is reported. This procedure combines the aerobic oxidation reaction and Wittig reaction in one pot, which avoids using of environmentally toxic oxidants and isolation of the intermediates. The simple procedure makes it very attractive for the synthesis of trisubstituted alkenes when alcohols are used as starting materials. A variety of trisubstituted alkenes as well as trifluoromethyl-substituted alkenes were obtained in moderate to good yields (up to 84%) with good E-selectivity (up to 99%). Georg Thieme Verlag Stuttgart.New York.

Capture of in situ generated diazo compounds or copper carbenoids by triphenylphosphine: Selective synthesis of trans-alkenes and unsymmetric azines via reaction of aldehydes with ketone-derived N-tosylhydrazones

Copper(II) acetylacetonate-catalyzed Wittig olefination reactions of aldehydes with ketone-derived N-tosylhydrazones are reported. A series of tosylhydrazones was investigated and our results showed that the carbon number of the alkyl chain influences the E-selecivity of the alkenes greatly. Alkenes could be obtained in moderate yields and excellent E-selectivity when the carbon numbers were up to two. Under metal-free conditions, triphenylphosphine was able to capture the in situ generated diazo compounds and the corresponding unsymmetrical azines were formed in good yields.

The reactivity of epoxides with lithium 2,2,6,6-tetramethylpiperidide in combination with organolithiums or grignard reagents

(Chemical Equation Presented) The scope and limitations of lithium 2,2,6,6-tetramethylpiperidide (LTMP)-modified reductive alkylation of epoxides is detailed. A variety of organolithiums are added to terminal and 2,2-disubstituted epoxides in the presence of LTMP to generate alkenes in a completely regio- and highly stereoselective manner. Arylated alkenes, dienes, allylsilanes, and enynes are accessed using this procedure. The methodology is applied in the synthesis of the roller leaf moth pheromone, (3E,5Z)-dodecadienyl acetate. The corresponding reaction without LTMP has also been examined, and a study using deuterated epoxides provides insight into the mechanism. In the presence of LTMP, Grignard reagents are also shown to produce E-alkenes directly from epoxides.

Carbolithiation of diphenylacetylene as a stereoselective route to (Z)-tamoxifen and related tetrasubstituted olefins

(Chemical Equation Presented) Carbolithiation of diphenylacetylene can be exploited to generate (E)-1-lithio-1,2-diphenylalkyl-1-enes which can be reacted in situ with triisopropylborate to stereoselectively provide (E)-1,2-diphenyl-1-alkylene boronic acids. These tetrasubstituted vinylboronic acids served as versatile intermediates for the generation of tetrasubstituted olefins with retention of stereochemistry. The application of this method for the stereoselective synthesis of (Z)-tamoxifen and related analogues is described.