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Our present study provides expedient methods for the synthesis of novel substituted indanes, pyrido[3,2,1-jk]carbazoles and pyrido[3,2,1-kl]phenothiazines utilizing intramolecular Friedel-Crafts cyclialkylations of synthesized heteroaryl alcohols. This methodology is realized by a three-step protocol involving first esterification of starting carboxylic acids to the corresponding esters, addition of Grignard reagents to give carbinol precursors and followed by Friedel-Crafts cyclizations of alcohols mediated by AlCl3/CH3NO2, PPA or P2O5-catalysts to furnish the desired polycycles in good to excellent yields of 65-85%. The designed protocol offers easy access to the pharmaceutically promising templates in good yields. The molecular structural elucidations of all newly obtained compounds have been proved by spectral and elemental analysis. [ABSTRACT FROM AUTHOR]

A series of neoflav-3-enes with a variety of natural substitution patterns was prepared from 1-(allyloxy)-2-[1-(aryl)vinyl]benzenes by Grubbs second generation (GII) catalyst-promoted ring-closing metathesis (67 - 99% yield). The 1-(allyloxy)-2-[1-(phenyl)vinyl]benzene substrates were accessible in yields of 52 - 94% from the corresponding 2-(allyloxy)acetophenones via a Grignard reaction and Lewis acid-promoted dehydration, either in a one pot process in the presence of Al(OTf)3 or in consecutive steps with CuSO4 as dehydrating agent. [ABSTRACT FROM AUTHOR]

This review focuses on the Bruylants reaction, namely the substitution with Grignard reagents of the cyano group in α-aminonitriles. This reaction goes through an iminium ion intermediate and proceeds with excellent stereoselectivities. The extension to organozinc reagents has been successfully applied. Triazoles such as benzotriazole and especially 1,2,3-triazole appear as relevant substitutes for the cyano leaving group. An alternative pathway for substitution of the cyano group involves an α-alkylation-decyanation sequence. Selected applications in organic synthesis are proposed. [ABSTRACT FROM AUTHOR]

A range of biologically important substituted 3-methylidene-2,3-dihydro-4H-pyrimido[2,1-b][1,3]benzothiazol- 4-ones and 3-methylidene-3,4-dihydro-2H-pyrimido[2,1-b][1,3]benzothiazol-2-ones was synthesized applying Horner-Wadsworth-Emmons methodology for the introduction of exo-methylidene bond onto a heterocyclic ring. Crucial in this approach, phosphonates were prepared by the reaction of ethyl 2-diethoxyphosphoryl-3- methoxyacrylate or ethyl 2-diethoxyphosphoryl-3-chloroacrylate with 2-aminobenzothiazoles, followed by addition of Grignard reagents to the obtained 3-diethoxyphosphoryl-4H-pyrimidobenzothiazol-4-ones or 3- diethoxyphosphoryl-2H-pyrimido[2,1-b][1,3]benzothiazol-2-ones, respectively. Surprising, ambident behavior of 2-aminobenzothiazoles towards ethyl 2-diethoxyphosphoryl-3-methoxyacrylate and ethyl 2- diethoxyphosphoryl-3-chloroacrylate is also discussed. [ABSTRACT FROM AUTHOR]

Two new Weinreb amide based bifunctional building blocks have been developed starting from meta and ortho-toluic acid for convenient access to meta- and ortho- positional isomers of FTY720. Julia olefination and Grignard reaction are the key steps used in the synthesis of 2 and 3. The bifunctional building blocks 4 and 5 are easy to scale-up and in addition to synthesis of 2 and 3, these building blocks would be valuable in search of a new amphiphiles, as the functionalities therein allows for change in the nature of polar head-group and lipophilic chain. [ABSTRACT FROM AUTHOR]

A general and efficient synthetic strategy has been developed for the total syntheses of clavaminols A, C and H in 5 to 7 steps starting from (R)-Garners aldehyde following Grignard reaction, Corey-Bakshi-Shibata asymmetric reduction and selective acetylation as key steps with 42 to 59% overall yields, respectively. [ABSTRACT FROM AUTHOR]

Thirteen mono-, bis- and trifluorinated bromobenzene derivatives have been coupled with cyclohexyl magnesium bromide or the corresponding lithiumchloride or lithiumbromide adducts. Iron, nickel and palladium complexes of the general formula [MCl2(dppx)] (x = (CH2)n, n = 1, 2, 3) have been used as the precatalysts. Palladium based catalysts give high yields of the coupling product with the Grignard reagent itself whereas lithium halides are needed as additives to achieve comparable efficiencies if nickel and iron catalysts are used. Yields also depend on the chain length of the bridging units and on the fact whether fluorine substituents are present in ortho position with respect to bromine. [ABSTRACT FROM AUTHOR]

A new method for the synthesis of substituted 3-alkyl-3,4-dihydroisocoumarins is described. o-(Oxiranylmethyl)benzonitriles, prepared from isovanillin in five steps, when reacted with nucleophiles such as sodium borohydride or phenylmagnesium chloride/CuI, undergo an intramolecular cyclization to yield the target compounds in good yields, in one pot. [ABSTRACT FROM AUTHOR]

The reactions of oligofunctionalized 1,1-dinaphthylmethanes with primary amines and ammonia are described. In the reaction of amines with 2,2',7,7'-tetrahydroxy- and 2,2'-dihydroxy-1,1-dinaphthylmethanes, the replacement of hydroxy groups by amino groups is accompanied by cleavage of ?-? bonds and elimination of a methylene unit. The regiodirection of the process is determined by the number and the nature of substituents in the dinaphthylmethane core. The catalytic amination of 2,2',7,7'-tetrakis(trifluoromethanesulfonyloxy)-1,1-dinaphthylmethane is not accompanied by destruction of the dinaphthylmethane core. The reaction selectivity and the product structure depend on the nature of the aminating reagent. [ABSTRACT FROM AUTHOR]

Facile procedures for the construction of fused indole-containing heteropolycycles 1a-f and 2a-c have been developed. The methodology involves Friedel-Crafts cyclialkylations of heteoraryl alkanols in the presence of both Brönsted (PPA) and Lewis (AlCl3/CH3NO2) acid catalysts. The starting alkanols 6a-f and 12a-c were smoothly obtained both by reactions of the corresponding carboxylic acid esters and the corresponding ketones with Grignard reagents. Overall, this approach allows for easy and efficient access to polycyclic indoles from easily synthesized precursors. [ABSTRACT FROM AUTHOR]

Despite good literature precedents, the addition of excess 2-biphenylmagnesium bromide to 4,5-dimethoxy-1,3-indanedione, followed by acid work-up, did not give the desired diol precursor to an Organic Molecule of Intrinsic Microporosity. Instead a dihydroisobenzofuran derivative was isolated in moderate yield and its structure characterised fully by single crystal X-ray crystallography. It is suggested that this product is formed by sequential Grignard addition, retroaldol reaction, a second Grignard addition and acid-mediated formation of the dihydroisobenzofuran ring. [ABSTRACT FROM AUTHOR]

Several multimethyl-substituted 1,3-dioxanes [trans-2,4,4,6-tetramethyl (1), r-2,4,4,c-5,t-6- pentamethyl- (2), r-2,4,4,t-5,t-6-pentamethyl (3) and trans-2,4,4,5,5,6-hexamethyl-1,3-dioxanes (4)] with 2,6-trans-disubstitution has been prepared via the Grignard reaction of the corresponding axial 2-methoxy-1,3-dioxanes. Inspection of their 13C NMR chemical shifts in respect of different substituent effects showed that 1 and 3 attain exclusively the 1,4-twist form whereas 2 and 4 still favor clearly the chair form due to the very strong steric interaction caused by the pseudo axial methyl groups at position 5. We also manage to equilibrate 1 and its cisepimer (5) although less than 1% of 4 was present at equilibrium. Thus only -?Go = 12.9±0.5 kJ mol-1 could be given and it compares well with some literature values. Since the conformational energy of 4-axial methyl group in 5 is 12.2 kJ mol-1 the ?H(1,4-CT) is equal to 25 kJ mol-1 again in good agreement with an earlier estimate. [ABSTRACT FROM AUTHOR]

Synthesis of paramagnetically modified deprenyl and oxotremorine is reported. Starting from 5- and 6-membered 2,5-disubstituted nitrones 1, 6 or 4-phenyl-2,5,5-trimethyl-1H-pyrroline 1-oxide 11 deprenyl or oxotremorine like nitroxides were synthesized via Grignard reactions. The corresponding pre-nitroxides with propargylamine structure were achieved by reduction of nitroxides followed by methylation. [ABSTRACT FROM AUTHOR]

The article focuses on the organic synthetic method, electrophilic amination of organomagnesium with reagents such as zinc, copper and lithium being the most viable option for the development of nitrogen compounds known as amines. It mentions organozinc compounds exhibit descent reactivity towards electrophilic reagents following the cavalent bonds they share with zinc and carbon. It also refers to a study conducted by the chemist researchers J. C. Fiaud and H. B. Kagan who found that the main Grignard reagents exhibited maximum reioselection favoring N-alkylation.

The ability of chiral methylmagnesium alkoxides derived from enantiopure alcohols to effect asymmetric addition to benzaldehyde has been investigated. The addition to benzaldehyde of chiral methylmagnesium alkoxides prepared from (-)-borneol, (+)-menthol or (+)-N-methylpseudoephedrine afforded virtually racemic 1-phenylethanol. Equilibration of a more complex species, generated upon addition of one molar equiv of MeMgBr to various molar quantities of the dilithio salt of (+)-pseudoephedrine before addition of benzaldehyde had a dramatic effect on both the reactivity of the reagent and the enantioselectivity of the addition. [ABSTRACT FROM AUTHOR]

A concise route for the synthesis of (+/-)-latifine and (+/-)-cherylline dimethyl ethers is reported. The key steps involved are the Michael type addition of p-methoxybenzene magnesium bromide to the (E)-1,2-dimethoxy-3-(2-nitrovinyl)benzene, reduction of the nitro intermediate obtained followed by the Pictet-Spengler cyclization and reductive N-methylation. [ABSTRACT FROM AUTHOR]