87947-80-6

Upstream product

• 695-12-5 vinylcyclohexane 
• 1663-39-4 tert-Butyl acrylate 
• 27784-76-5 tert-butyl diethylphosphonoacetate 
• 2043-61-0 cyclohexanecarbaldehyde 
• 1048364-45-9 tert-butyl 2-[3,5-bis(trifluoromethyl)phenylsulfonyl]acetate 
• 5292-43-3 bromoacetic acid tert-butyl ester 
• 120823-62-3 tert-butyl (trimethylgermyl)acetate 
• 87947-72-6 (E)-3-Cyclohexyl-2-trimethylsilanyl-acrylic acid tert-butyl ester 

Downstream Products

• 960197-75-5 t-butyl 3-cyclohexyl-3-N,N-diisopropylaminopropionate 

Relevant academic research and scientific papers

Thermodynamic Understanding of an Aza-Michael Reaction Enables Five-Step Synthesis of the Potent Integrin Inhibitor MK-0429

We describe a general strategy for the aza-Michael addition of nucleophilic heterocycles into β-substituted acrylates using potassium tert-butoxide as catalyst. Demonstrating that the reaction is under thermodynamic control underpins optimization efforts and enables rapid exploration of the substrate scope, with yields ranging from 55% to 94%. We further leverage these lessons in a significantly shortened synthesis of MK-0429, a potent pan-integrin inhibitor previously taken into human clinical trials for the treatment of prostate cancer and osteoporosis.

Synthesis of Linear (Z)-α,β-Unsaturated Esters by Catalytic Cross-Metathesis. The Influence of Acetonitrile

Kinetically controlled catalytic cross-metathesis reactions that generate (Z)-α,β-unsaturated esters selectively are disclosed. A key finding is that the presence of acetonitrile obviates the need for using excess amounts of a more valuable terminal alken

Highly (E)-selective wadsworth-emmons reactions promoted by methylmagnesium bromide

(Chemical Equation Presented) An experimentally simple protocol for the very highly (E)-selective Wadsworth-Emmons reaction [(E):(Z) selectivities in excess of 180:1 in some cases] of a range of straight-chain and branched aliphatic, substituted aromatic, and base-sensitive aldehydes via reaction with an alkyl diethylphosphonoacetate and MeMgBr is reported.

3,5-Bis(trifluoromethyl)phenyl sulfones for the highly stereoselective Julia-Kocienski synthesis of α,β-unsaturated esters and weinreb amides

The 3,5-bis(trifluoromethyl)phenyl (BTFP) sulfones tert-butyl α-(BTFPsulfonyl)acetate (4) and Weinreb α-(BTFPsulfonyl)-acetamide (5) have successfully been employed in the Julia-Kocienski olefination of aldehydes with K2CO3 as the base at 120°C in DMF under solid/liquid phase-transfer catalysis conditions to afford α,β- unsaturated esters and Weinreb amides, respectively. The corresponding products were obtained in good yields and with high E stereoselectivities (E/Z up to >99:1), especially in the case of the amides. A detailed computational study of the Julia-Kocienski olefination with BTFP sulfone 4 was carried out and confirmed the existence of an equilibrium in the initial addition of the sulfone enolate to the aldehyde and, in contrast to other proposed mechanisms, a non-concerted final elimination of SO2 and 3,5-bis-(trifluoromethyl) phenoxide. A plausible explanation for the high E diastereoselectivity observed in the reaction has been suggested based on kinetic considerations at spirocyclic TS2 and thermodynamic factors during the elimination after TS2. ESI-MS studies carried out during the olefination reaction of benzaldehyde with BTFP sulfone 4 were used to characterize the sulfone enolate and the intermediate assumed for the reaction mechanism. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Lithium diisopropylamide-mediated reactions of imines, unsaturated esters, epoxides, and aryl carbamates: Influence of hexamethylphosphoramide and ethereal cosolvents on reaction mechanisms

Several reactions mediated by lithium diisopropylamide (LDA) with added hexamethylphosphoramide (HMPA) are described. The N-isopropylimine of cyclohexanone lithiates via an ensemble of monomer-based pathways. Conjugate addition of LDA/HMPA to an unsaturated ester proceeds via diand tetra-HMPA-solvated dimers. Deprotonation of norbornene epoxide by LDA/HMPA proceeds via an intermediate metalated epoxide as a mixed dimer with LDA. Ortholithiation of an aryl carbamate proceeds via a mono-HMPA-solvated monomer-based pathway. Dependencies on THF and other ethereal cosolvents suggest that secondary-shell solvation effects are important in some instances. The origins of the inordinate mechanistic complexity are discussed.

The one-pot Wittig reaction: A facile synthesis of α,β- unsaturated esters and nitriles by using nanocrystalline magnesium oxide

Nanocrystalline magnesium oxide was found to be an effective heterogeneous, solid base catalyst for the one-pot Wittig reaction to afford α,β-unsaturated esters and nitriles in excellent yields with high E-stereoselectivity in the presence of triphenylphosphine under mild conditions.

Wittig-type olefination catalyzed by PEG-telluride

Soluble poly(ethylene glycol) (PEG)-supported telluride 2 was designed and synthesized for catalytic Wittig-type reactions. It was found that the catalytic loading could be reduced from 20 to 2 mol % by the introduction of PEG (even to 0.5 mol % when some telluride salts were used as the catalyst). Under the catalytic reaction conditions, a wide variety of aldehydes with different structures could react with bromoacetate to afford β-substituted or α,β-disubstituted unsaturated esters in high yields with excellent E-stereoselectivity. The modified process, by using sodium bisulfite instead of triphenyl phosphite, represented a very simple product isolation procedure. The roles of PEG for promoting the ylide formation and stabilizing the catalytic species were disclosed. The mechanism was also studied.

A practical catalytic Wittig-type reaction

Soluble PEG-supported telluride 2 was synthesized and found to be an effective catalyst for the catalytic Wittig-type reaction to give a variety of α,β-unsaturated esters in high yields with excellent E-stereoselectivity in the presence of sodium bisulfite as well as triphenyl phosphite.

Peterson Olefination Reaction Using (Trimethylgermyl)acetate. Stereoselective Synthesis of (E)-2-Alkenoic Acid Esters

Peterson-type reaction of (trimethylgermyl)acetates 1 with aldehydes and ketones 2 gave stereoselectively (E)-2-alkenoic acid esters (E)-4 after stirring at -78 deg C and warming to room temperature.High yields of the reaction intermediates threo- and erythro-3-hydroxy-2-(trimethylgermyl)alkanoic acid esters 3 were obtained when the reaction was quenched at -78 deg C.The paths for conversion of threo-3 and erythro-3 to (E)-4 are discussed.