Merck research group

The biomimetic approach to the core skeleton of C-nor-D-homosteroid was first developed by the Merck research group (Scheme 2.1) [16]. In the Merck procedure,... 

The first practical and efficient asymmetric alkylation by use of chiral phase-transfer catalysts was the alkylation of the phenylindanone 15 (R1=Ph), reported by the Merck research group in 1984.114-161 By use of the quaternary ammonium salt 7 (R=4-CF3i X=Br) derived from cinchonine, the alkylated products 16 were obtained in excellent yield with high enantiomeric excess, as shown in... 

The rhodium(II)-induced tandem cyclization-cycloaddition process has also been applied with notable success to the core structure of zaragozic acid by the Merck research group <94TL9185>. Zaragozic acid A (20) was discovered as a metabolite from an unidentified... 

In 1984, the first successful monumental use of cinchona PTC for asymmetric a-substitution of carbonyls was reported by Dolling and coworkers of the Merck research group (Scheme 6.1) [8], In this work, cinchoninium salt (1) was employed in the catalytic asymmetric methylation of 6,7-dichloro-5-methoxy-2-phenyl-l-indanone (2) under phase-transfer conditions. The methylated product 3, which was finally transformed to (+ )-indacrinone through three further steps, was obtained in 95% conversion with 92% enantiomeric excess (ee). Through the systematic investigation, the group reported the relationship between the chemical/optical yield and the reaction variables (e.g., amount or concentration of each chemical species, halide of... 

Klapars and Waldman, of the Merck research group, reported a transition metal-free a-arylation of aliphatic nitriles with heteroaryl halides using KHMDS or NaHMDS as bases in a toluene/THF mixture at 0-25 °C. However, this protocol was strictly limited to the conversion of electronically activated heteroaryl halides [236]. 

Five years after the successful application of the cinchonine-derived quaternary ammonium catalyst 3 by the Merck research group, O Donnell and... 

Several asymmetric conjugate additions under PTC conditions have been studied as a useful approach to installing chiral functionalised carbon skeletons. In 1986, Conn and coworkers at the Merck research group... 

A Merck research group discovered that the cross-coupling reaction between aryl halides and vinylogous amides could take place under the catalysis of Pd/DavePhos. When 1,2-dibromobenzene was used, a cascade intermolecular C-N bond coupling and intramolecular Heck reaction occurred to provide 2,3-disubstituted indoles (Scheme 2) [25]. 

Cinchona Alkaloid-Derived Quaternary Ammonium Salts The first successful application of cinchona-based quaternary ammonium salts as chiral phase-transfer catalysts was conducted by the Merck research group in 1984 [16]. Dolling and coworkers reported the N-p-trifluoromethylbenzylcinchoninium bromide 11a for the highly enantioselective alkylation of indanone derivatives imder phase-transfer conditions (Figure 12.3). 

This method was later adapted for the large-scale preparation of the LTD4 antagonist 64 by another Merck Process Research group (Figure 3.11) [21], Conversion of a methyl benzoate to the corresponding acetophenone was required. Formation of the tertiary alcohol was again minimized with the addition of H M DS and excellent reaction performance was achieved. 

Merck Research Laboratories, Discovery Predinical Sciences, Global Chemistry—Structure Elucidation Group, Summit, New Jersey, 07901, USA... 

Chiral /3,/3-diaryIpropionic acid moieties are often found in compounds showing biological activities, such as antiarrhythmics vasodilators antidepressives " , antihistamines and controllers of cerebral insufficiency ". In the course of synthetic studies of chiral -diaryIpropionic acid derivatives, Merck researchers developed stereoselective conjugate addition of aryllithium reagents to the a,/ -unsaturated fert-butyl esters 18 bearing a chiral imidazolidine or oxazolidine auxiliary at the ortho position of an aryl group. The addition furnished chiral -diaryIpropionic acid derivatives 19 with... 

In 1986, a research group from Merck discovered that the soil bacterium Strepto myces cattleya was able to elaborate two fluorinated metabolites. S. cattleya is... 

Immunosuppressant (-)-FK-S06 (2). This 23-membered lactone-lactam resembles cyclosporin A, a macrocyclic polypeptide, in that they both inhibit immune responses to transplantation, but FK-506 seems to be more active. The total synthesis of (- )-FK-506 has been achieved by a process research group at Merck.1 The cyclization to a carboxamide was carried out with Mukaiyama s reagent (1) under high dilution in 81% yield. The most unusual feature of 2 is the presence of a three-keto sequence at C8, C9, and C,(l (hemiketal). 

Merck process research group developed a short and efficient synthesis of 3-(2,2,2-trifluoroethyl)-hexahydro-2//-l,4-diazepin-2-one 85 as part of an ongoing research program to identify peptidase inhibitors <07S2779>. 

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