Synthesis of tetrasubstituted

Indium trichloride has been found to catalyze the synthesis of tetrasubstituted... 

Scheme 12 Synthesis of tetrasubstituted pyrroles by coupled domino processes...

Such a strategy follows the philosophy of resin capture, as introduced by Armstrong and Keating Keating TA, Armstrong RW. Postcondensation modifications of Ugi four-component condensation products 1-isocyano-cyclohexane as a convertible isocyanide. Mechanism of conversion, synthesis of diverse structures, and demonstration of resin capture. J Am Chem Soc 1996 118 2574-2583. See also Brown SD, Armstrong RW. Synthesis of tetrasubstituted ethylenes on solid support via resin capture. J Am Chem Soc 1996 118 6331-6332. 

Scheme 2.59. Domino aldol addition/aldol condensation process for the synthesis of tetrasubstituted cyclopent-2-en-1 -ones.

Tejedor and coworkers have utilized a combination of two domino processes for a microwave-promoted synthesis of tetrasubstituted pyrroles [344]. The protocol combines two coupled domino processes the triethylamine-catalyzed synthesis of enol-protected propargylic alcohols and their sequential transformation into pyrroles through a spontaneous rearrangement from 1,3-oxazolidines (Scheme 6.183). Overall, these two linked and coupled domino processes build up two carbon-carbon bonds, two carbon-nitrogen bonds, and an aromatic ring in a regioselective and efficient manner. The tetrasubstituted pyrroles could be directly synthesized from the enol-protected propargylic alcohols and the primary amines by microwave irradia-... 

The regioselectivity of palladium-catalyzed additions of organoboronic acids to unsymmetrical alkynes is strongly dependent on steric and electronic effects (Scheme 12).62 Multi-component reaction has been reported for the synthesis of tetrasubstituted alkenes.58 The aryl group from an aryl iodide is generally added to the less hindered... 

Scheme 2.64 Samarium-mediated synthesis of tetrasubstituted furan 211 (L= PPh3).

DFT Based Analysis for The Regio- and Stereoselective Synthesis of Tetrasubstituted Isoxazolidines From Cinnamoyl Piperidine Derivatives... 

However, a more exciting application of this reaction is the oxazoline-directed synthesis of axially chiral biaryls. The oxazoline system not only activates the ortho-methoxy group for nucleophilic displacement but also determines the stereochemical outcome of the reaction. This provides a convenient method for the introduction of axial-chirality. Meyers group continues their earlier lead on this subject with reports of the stereoselective synthesis of tetrasubstituted biphenyls 391,392 examples are shown in Table 8.29 (Scheme 8.154). The best... 

TABLE 6. Synthesis of tetrasubstituted olefins (151) by the reaction of 1-chlorovinyl p-tolyl sulfoxide (147) with ArMgBr followed by addition of electrophiles... 

Analogous chemistry has been reported with a-chlorosulfoxides, though much less studied. Initial y-dehydrochlorination yields thiirane S-oxides, but from these intermediates two alternative pathways can occur leading to sulfenales and/oi alkenes. The method was shown to be efficient for the synthesis of tetrasubstituted alkenes [417]. 

Balalaie, S. and Arabanian, A., One-pot synthesis of tetrasubstituted imidazoles catalyzed by zeolite HY and silica gel under microwave irradiation, Green Chem., 2000,2, 274-276. 

Balalaie, S., Hashemi, M.M. and Akhbari, M., A novel one-pot synthesis of tetrasubstituted imidazoles under solvent-free conditions and microwave irradiation, Tetrahedron Lett., 2003, 44, 1709-1711. 

Balalaie, S., Al abaman, A. and Hashtroudi, M.S., Zeolite HY and silica gel as new and efficient heterogenous catalysts for the synthesis oftriarylimidazoles under microwave irradiation, Monatsh. Chem., 2000,131,945— 948 Balalaie, S. and Arabanian, A., One-pot synthesis of tetrasubstituted imidazoles by zeolite HY and silica gel under microwave irradiation, Green Chem., 2000, 2, 274-276. 

It should be pointed out that while the dihalocyclopropane-allene conversion discussed here represents the best general synthesis of allenes, occasional problems due to the formation of side products have been reported. An example is the formation of the bicyclobutane (16) along with the expected allene (equation 53).166 The method is especially unsuitable for the synthesis of tetrasubstituted allenes. Steri-cally demanding substituents on the dihalocyclopropanes are believed to be responsible for the change of course of the reaction. 

Scheme 2.32. Solid-phase synthesis of tetrasubstituted imidazoles.

Nowadays new imidazolin-2-ylidene substituted Ru-catalysts like 35 are under investigation, which show increasing activity even at low temperatures. Advantageously they show no sensitivity to air or to moisture. Potential activity is expected to result from higher Lewis basicity and steric demand. They give good results even in the synthesis of tetrasubstituted cycloalkenes.12... 

A simple one-pot synthesis of tetrasubstituted thicnol 2,3-/ thiophenes 192 by condensation 1,3-diketones with CS2, and alkylating agents carrying an EWG such as C02Et, COR, or CN in the presence of anhydrous KF as condensation promoter in anhydrous DMF was described (Scheme 36) [47,48], The authors examined several other solvents such as anhydrous dioxane, THF, or MeCN, but they were found to be ineffective. 

Scheme 15.5 Synthesis of tetrasubstituted pyrroles by microwave-assisted Paal-Knorr reaction.

Stauffer SR, Katzenellenbogen JA, Solid-phase synthesis of tetrasubstituted pyrazoles, novel ligands for the estrogen receptor, J. Comb. Chem., 2 318-329, 2000. 

Brown SD, Armstrong RW, Synthesis of tetrasubstituted ethylenes on solid support via resin capture, J. Am. Chem. Soc., 118 6331-6332, 1996. 

A highly chemo- and regioselective [2 + 2 + 2] sequential cycloaddition of alkynes and 1,3-butadiynes catalyzed by Pd(0) complexes as an elegant de novo synthesis of tetrasubstituted benzenes 216 (Scheme 88) and pen-... 

Claiborne CF, Liverton NJ, Nguyen KT (1998) An efficient synthesis of tetrasubstituted imidazoles from A-(2-oxo)-amides. Tetrahedron Lett 39 8939-8942... 

The four-component, two-step synthesis of tetrasubstituted imidazoles 259 is described in Scheme 45 [90]. Initially, all the four components were heated together resulting, however, in lower yields because of the competing formation of... 

The synthesis of tetrasubstituted naphthalenes consisting of thiophene 33 were reported using palladium catalyzed reactions of aryl iodides and internal alkynes <03JOC6836>. 

Olefination of acylsilanes is expected to become a useful method for the preparation of vinylsilanes, which are a powerful synthetic tool . Olefination of the acylsilanes 135 with ynolates provides the -silyl-a,/S-unsaturated esters 136 in high yields with high Z-selectivity (equation 56) . In most cases, the E isomers could not be detected by H NMR and HPLC. This is the first general method for the stereoselective synthesis of tetrasubstituted olefins. 

The previous cycloaddition reaction discussed is believed to proceed through an aldimine anion (19). Such delocalized anions can also be generated by treatment of suitable aldimines with a strong base. Subsequent cyclocondensation with a nitrile produces imidazoles [25-28]. The 2-azaallyl lithium compounds (19) are made by treatment of an azomethine with lithium diiso-propylamide in THF-hexane ( 5 1) (Scheme 4.2.9) [29. To stirred solutions of (19) one adds an equimolar amount of a nitrile in THF at —60°C. Products are obtained after hydrolysis with water (see also Section 2.3). If the original Schiff base is disubstituted on carbon, the product can only be a 3-imidazoline, but anions (19) eliminate lithium hydride to give aromatic products (20) in 37-52% yields (Scheme 4.2.9). It is, however, not possible to make delocalized anions (19) with R = alkyl, and aliphatic nitriles react only veiy reluctantly. Examples of (20) (Ar, R, R, yield listed) include Ph, Ph, Ph, 52% Ph, Ph, m-MeCeUi, 50% Ph, Ph, p-MeCeUi, 52% Ph, Ph, 3-pyridyl, 47% Ph, Ph, nPr, 1% [25]. Closely related is the synthesis of tetrasubstituted imidazoles (22) by regioselective deprotonation of (21) and subsequent reaction with an aryl nitrile. Even belter yields and reactivity are observed when one equivalent of potassium t-butoxide is added to the preformed monolithio anion of (21) (Scheme 4.2.9) [30]. 

The anions of nitroalkanes (nitronates) can be used as precursors in a connective and regiospecific synthesis of tetrasubstituted alkenes. They are easily formed on reaction with LiOMe and undergo oxidative dimerization in the presence of bromine. The resultant 1,2-dinitroalkanes (Scheme 37) participate in a reductive elimination involving an rc1 radical chain mechanism when irradiated in the presence of Na2S, PhSNa or the lithium nitronate derived from 2-nitropropane. 

R. Bossio and co-workers developed a novel method for the synthesis of tetrasubstituted furan derivatives. The Passerini reaction between arylglyoxals, isocyanides, and cyanoacetic acids led to the formation of A/-substituted 3-aryl-2-cyanoacetoxy-3-oxopropionamides, which in the presence of amine bases underwent a Knoevenagei condensation providing A/-substituted 3-aryl-cyano-2,5-dihydro-5-oxofuran-2-carboxamides. 

Sano, S., Takehisa, T., Ogawa, S., Yokoyama, K., Nagao, Y. Stereoselective synthesis of tetrasubstituted (Z)-alkenes from aryl alkyl ketones utilizing the Horner-Wadsworth-Emmons reaction. Chem. Pharm. Bull. 2002, 50, 1300-1302. 

---