87580-60-7

Upstream product

• 917-64-6 methyl magnesium iodide 
• 106596-74-1 3-isobutoxy-1-(4-methoxy-phenyl)-propenone 
• 15960-71-1 rac-2-(4-methoxyphenyl)but-3-yn-2-ol 
• 7020-80-6 acetaldehyde N-tert-butylimine 
• 100-06-1 1-(4-methoxyphenyl)ethanone 
• 235101-21-0 (R)-2-(4-methoxyphenyl)-2-methylbut-3-en-1-ol 
• 790260-90-1 (R)-(+)-2-(methoxycarbonyl)-2-(4-methoxyphenyl)propionic acid 
• 235101-19-6 (R)-(+)-3-(methoxymethoxy)-2-(4-methoxyphenyl)-2-methylpropanal 
• 235101-20-9 1-Methoxy-4-((R)-1-methoxymethoxymethyl-1-methyl-allyl)-benzene 
• 959903-74-3 methyl (R)-(+)-3-hydroxy-2-(4-methoxyphenyl)-2-methylpropionate 
• 235101-25-4 (R)-(+)-3-(methoxymethoxy)-2-(4-methoxyphenyl)-2-methylpropanol 
• 235101-18-5 methyl (R)-(+)-3-(methoxymethoxy)-2-(4-methoxyphenyl)-2-methylpropionate 
• 814-49-3 diethyl chlorophosphate 
• 123-73-9 trans-Crotonaldehyde 

Downstream Products

• 120554-70-3 (E,E)-5-(4-methoxyphenyl)-2,4-hexadienoic acid 4-nitrophenyl ester 
• 1443764-49-5 3-(4-methoxyphenyl)-3-methyl-4-nitrobutanal 
• 1443764-59-7 3-(4-methoxyphenyl)-3-methyl-4-nitrobutan-1-ol 
• 60573-60-6 (E)-1-methoxy-4-(penta-2,4-dien-2-yl)benzene 

Relevant academic research and scientific papers

Stereodefined rhodium-catalysed 1,4-H/D delivery for modular syntheses and deuterium integration

Deuterium-incorporated compounds are of high interest owing to their importance in the pharmaceutical industry, organic synthesis and materials science. So far, the integration of deuterium into the inert, saturated magic methyl or methylene groups of covalent molecules remains challenging. Here, we present a 1,4-H delivery of allylic metallic species to provide a highly stereoselective and straightforward approach to 3-methyl-2(E)-enals or -enones from readily available 2,3-allenols and organoboronic acids. The reaction accommodates many synthetically versatile functional groups as well as multi-pharmacophores, and is not limited to the formation of 3-methyl derivatives. By applying 1,4-H or D delivery, deuterium atom(s) from differently deuterated allenols can be edited into the methyl or methylene groups of versatile organic skeletons, resulting in the efficient formation of 4-monodeuterated, 1,4- and 4,4-doubly deuterated, and 4,4,4-triply deuterated 2(E)-enals or -enones. These powerful platform molecules can provide straightforward paths to other deuterated compounds for different purposes. [Figure not available: see fulltext.].

Highly Selective and Catalytic Generation of Acyclic Quaternary Carbon Stereocenters via Functionalization of 1,3-Dienes with CO2

The catalytic asymmetric functionalization of readily available 1,3-dienes is highly important, but current examples are mostly limited to the construction of tertiary chiral centers. The asymmetric generation of acyclic products containing all-carbon quaternary stereocenters from substituted 1,3-dienes represents a more challenging, but highly desirable, synthetic process for which there are very few examples. Herein, we report the highly selective copper-catalyzed generation of chiral all-carbon acyclic quaternary stereocenters via functionalization of 1,3-dienes with CO2. A variety of readily available 1,1-disubstituted 1,3-dienes, as well as a 1,3,5-triene, undergo reductive hydroxymethylation with high chemo-, regio-, E/Z-, and enantioselectivities. The reported method features good functional group tolerance, is readily scaled up to at least 5 mmol of starting diene, and generates chiral products that are useful building blocks for further derivatization. Systemic mechanistic investigations using density functional theory calculations were performed and provided the first theoretical investigation for an asymmetric transformation involving CO2. These computational results indicate that the 1,2-hydrocupration of 1,3-diene proceeds with high π-facial selectivity to generate an (S)-allylcopper intermediate, which further induces the chirality of the quaternary carbon center in the final product. The 1,4-addition of an internal allylcopper complex, which differs from previous reports involving terminal allylmetallic intermediates, to CO2 kinetically determines the E/Z- and regioselectivity. The rapid reduction of a copper carboxylate intermediate to the corresponding silyl-ether in the presence of Me(MeO)2SiH provides the exergonic impetus and leads to chemoselective hydroxymethylation rather than carboxylation. These results provide new insights for guiding further development of asymmetric C-C bond formations with CO2

Rh-Catalyzed Asymmetric Hydrogenation of β-Branched Enol Esters for the Synthesis of β-Chiral Primary Alcohols

An asymmetric hydrogenation of β-branched enol esters has been developed for the first time, providing a new route for the synthesis of β-chiral primary alcohols. Using a (S)-SKP-Rh complex bearing a large bite angle and enol ester substrates possessing an O-fomyl directing group, the desired products were obtained in quantitative yields and with excellent enantioselectivities.

Synthetic approaches to mono- and bicyclic perortho-esters with a central 1,2,4-trioxane ring as the privileged lead structure in antimalarial and antitumor-active peroxides and clarification of the peroxide relevance

The synthesis of 4-styryl-substituted 2,3,8-trioxabicyclo[3.3.1]nonanes, peroxides with the core structure of the bioactive 1,2,4-trioxane ring, was conducted by a multistep route starting from the aryl methyl ketones 1a-1c. Condensation and reduction/oxidation delivered enals 4a-4c that were coupled with ethyl acetate and reduced to the 1,3-diol substrates 6a-6c. Highly diastereoselective photooxygenation delivered the hydroperoxides 7a-7c and subsequent PPTS (pyridinium-p-toluenesulfonic acid)-catalyzed peroxyacetalization with alkyl triorthoacetates gave the cyclic peroxides 8a-8e. These compounds in general show only moderate antimalarial activities. In order to extend the repertoire of cyclic peroxide structure, we aimed for the synthesis of spiro-perorthocarbonates from orthoester condensation of β-hydroxy hydroperoxide 9 but could only realize the monocyclic perorthocarbonate 10. That the central peroxide moiety is the key structural motif in anticancer active GST (glutathione S-transferase)-inhibitors was elucidated by the synthesis of a 1,3-dioxane 15-with a similar substitution pattern as the pharmacologically active peroxide 11-via a singlet oxygen ene route from the homoallylic alcohol 12.

Ruthenium-catalyzed oxidation of allyl alcohols with intermolecular hydrogen transfer: Synthesis of α,β-unsaturated carbonyl compounds

Ruthenium-catalyzed oxidation of multisubstituted allyl alcohols in the presence of benzaldehyde gives enals or enones in good yields. Unlike the commonly reported ruthenium-catalyzed isomerization reaction of allyl alcohols to give saturated ketones, an intermolecular rather than intramolecular hydrogen transfer is involved in this transformation. This reaction offers an efficient, mild, and high-yielding method for the preparation of substituted α,β-unsaturated compounds.

Pd-arylurea complexes for the Heck arylation of crotonic and cinnamic substrates

A catalyst consisting of the 1:2 complex of Pd(OAc)2 (1 mol %) with N-(4-carbethoxy)-phenylurea promotes the Heck arylation of a range of crotonic and cinnamic substrates, including aldehydes, ketones, esters, and nitriles, with electron-rich - but not electron-deficient - aryl iodides.

Selective reactivity of electron-rich aryl iodides in the Heck arylation of disubstituted alkenes catalyzed by palladium-arylurea complexes

A catalyst consisting of 1 mol % of the 1:2 complex of Pd(OAc)2 with N-(4-carbethoxyphenyl)urea promotes the Heck arylation of 2- or 3-substituted, conjugated esters, nitriles, aldehydes, and ketones (an uncharacteristically broad range of substrates), but only with electron-rich aryl iodides (an uncharacteristically narrow range of halides).

Total synthesis of (-)-sporochnol A, the fish deterrent, from a chiral malonate

From a single chiron, the homochiral benzylic malonic acid ester (R)- (+)-2 available with high enantiomeric excess by enzymatic hydrolysis (PLE acetonic powder), enantiomerically pure (-)-sporochnol A 1 was prepared. This versatile method allows preparation of sporochnol 1, via aldehydes 7 and 15, in good overall yield.

Pentadienyl carboxamide derivatives as antagonists of platelet-activating factor

A series of N-[4-(3-pyridinyl)butyl]-5,5-disubstituted-pentadienamides was prepared and evaluated for PAF-antagonist activity. Compounds were assayed in vitro in a PAF-binding assay employing washed, whole dog platelets as the receptor source and in vivo after intravenous or oral administration for their ability to prevent PAF-induced bronchoconstriction in guinea pigs. Criteria required for good oral activity in the latter model include an (E,E)-5-phenyl-2,4-pentadienamide, a second phenyl or a four- or five-carbon alkyl moiety in the 5-position of the diene, and an (R)-[1-alkyl-4-(3-pyridinyl)butyl] substituent on the carboxamide nitrogen atom. The alkyl substituent on this side chain can be methyl, ethyl, or cyclopropyl. Two members of this series, [R-(E)]-5,5-bis(4-methoxyphenyl)-N-[1-methyl-4-(3-pyridinyl)butyl]-2,4- pentadienamide (31) and [R-(E,E)]-5-(4-methoxyphenyl)-N-[1-methyl-4-(3-pyridinyl)butyl]-2,4- decadienamide (58), were selected for further pharmacological evaluation. Both were found to be substantially longer acting after oral administration than the corresponding S enantiomers in the guinea pig bronchoconstriction assay. A second in vivo model used to evaluate PAF antagonists determines the ability of test compounds to decrease the area of skin wheals induced by an intradermal injection of PAF. In this model, using both rats and guinea pigs, compounds 31 and 58 were found to be as active as the reference PAF antagonist 3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3- a][1,4]diazepin-2-yl]-1-(4-morpholinyl)-1-propanone (45).

Pentadieneamides

Compounds of the formula STR1 Y is O ir S, *A is paraphenylene or *----(CH2)n----(X)m --(CH2)r ----, X is O, S or --CH=CH--, n or r, independently, are integers from 0 to 3, s is an integer from 0 to 1, m is an integer from 0 to 1, provided that when m is 1, n+s must be at least 2, R1 and R2, independently, are hydrogen, lower alkyl, cycloalkyl, lower alkenyl, Het, aryl, R3, R4 and R8, independently, are hydrogen, lower alkyl, aryl, R5 and R6, independently, are hydrogen or lower alkyl, R7 is hydrogen, lower alkyl, cycloalkyl, Het-lower alkyl or aryl, Het is a monocyclic 5- or 6-membered hetero aromatic or a bicyclic heteroaromatic radical containing one or two hetero atoms selected from nitrogen, oxygen and sulfur, which radical may be substituted by lower alkyl, halogen or aryl, and the asterisk denotes the point of attachment, and when R6 and R7 are different, their enantiomers and racemic mixtures thereof, when R1 and R2 are different, their geometric isomers, and pharmaceutically acceptable acid addition salts thereof, are described. The compounds of formula I exhibit activity as platelet activating factor (PAF) antagonists and are, therefore, useful in disease states characerized by excess platelet activating factor or for the prevention and treatment of cardiovascular disease, pulmonary diseases, immunological disorders, inflammatory diseases, dermatological disorders, shock or transplant rejection.