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Showing papers in "Journal of Organic Chemistry in 1998"


Journal ArticleDOI
TL;DR: In this paper, the palladium-catalyzed coupling of 2-iodoaniline and the corresponding N-methyl, -acetyl, and -tosyl derivatives with a wide variety of internal alkynes provides 2,3-disubstituted indoles in good-to-excellent yields.
Abstract: The palladium-catalyzed coupling of 2-iodoaniline and the corresponding N-methyl, -acetyl, and -tosyl derivatives with a wide variety of internal alkynes provides 2,3-disubstituted indoles in good-to-excellent yields. The best results are obtained by employing an excess of the alkyne and a sodium or potassium acetate or carbonate base plus 1 equiv of either LiCl or n-Bu4NCl, occasionally adding 5 mol % PPh3. The yields with LiCl appear to be higher and more reproducible than those obtained with n-Bu4NCl. The process is quite general as far as the types of substituents which can be accommodated on the nitrogen of the aniline and the two ends of the alkyne triple bond. The reaction is quite regioselective, placing the aryl group of the aniline on the less sterically hindered end of the triple bond and the nitrogen moiety on the more sterically hindered end. This methodology readily affords 2-silylindoles, which can be easily protodesilylated, halogenated, or reacted with alkenes and Pd(OAc)2 to produce 3-su...

527 citations


Journal ArticleDOI
TL;DR: Biginelli's initial one-pot reflux of â-keto ester 2, aryl aldehyde 3, and urea, 4, with catalytic acid in a protic solvent frequently afforded low (20-50%) yields as mentioned in this paper.
Abstract: In the past decade, 4-aryl-dihydropyrimidinones 1 have emerged as the integral backbones of several calcium channel blockers, antihypertensive agents, and alpha-1 a-antagonists.1 Strategies for the synthesis of the dihydropyrimidinone nucleus have varied from one-pot to multistep approaches. Biginelli’s initial one-pot reflux of â-keto ester 2, aryl aldehyde 3, and urea, 4, with catalytic acid in a protic solvent frequently afforded low (20-50%) yields.2,3 Subsequent multistep syntheses produced somewhat higher yields but lacked the simplicity of the one-pot, one-step synthesis.3

464 citations


Journal ArticleDOI
TL;DR: In this article, the entropic component of the free energy of assembly for multiparticle hydrogen-bonded aggregates is analyzed using a model based on balls connected by rigid rods or flexible strings.
Abstract: The entropic component of the free energy of assembly for multiparticle hydrogen-bonded aggregates is analyzed using a model based on balls connected by rigid rods or flexible strings. The entropy of assembly, ΔS, is partitioned into translational, rotational, vibrational, and conformational components. While previously reported theoretical treatments of rotational and vibrational entropies for assembly are adequate, treatments of translational entropy in solution and of conformational entropyoften the two largest components of ΔSare not. This paper provides improved estimates and illustrates the methods used to obtain them. First, a model is described for translational entropy of molecules in solution (ΔStrans(sol)); this model provides physically intuitive corrections for values of ΔStrans(sol) that are based on the Sackur−Tetrode equation. This model is combined with one for rotational entropy to estimate the difference in entropy of assembly between a 4-particle aggregate and a 6-particle one. Second,...

369 citations


Journal ArticleDOI
TL;DR: In this paper, the C−H bond at their 2'-position was cleaved in the presence of a catalyst system of Pd(OAc)2 and Cu(OAC)2 with a base under air.
Abstract: N-(2‘-Phenylphenyl)benzenesulfonamides react with acrylate esters accompanied via cleavage of the C−H bond at their 2‘-position in the presence of a catalyst system of Pd(OAc)2 and Cu(OAc)2 and a base under air to produce 5,6-dihydro-5-(benzenesulfonyl)phenanthridine-6-acetate derivatives in high yields. The reactions of benzoic acid with butyl acrylate and styrene can also give 3-[(butoxycarbonyl)methyl]phthalide and 3-phenylisocoumarin, respectively.

322 citations



Journal ArticleDOI
TL;DR: In this paper, an efficient procedure for the oxidation of primary and secondary allylic and benzylic alcohols to aldehydes and ketones, respectively, was achieved using catalytic Pd(OAc)2 in dimethyl sulfoxide (DMSO) with oxygen gas as the sole reoxidant of the palladium.
Abstract: An efficient procedure for the oxidation of primary and secondary allylic and benzylic alcohols to aldehydes and ketones, respectively, has been achieved using catalytic Pd(OAc)2 in dimethyl sulfoxide (DMSO) with oxygen gas as the sole reoxidant of the palladium. Secondary substrates show increased reaction rates and improved yields with the addition of 2 equiv of NaHCO3. The reactions are free of acetal/ketal and ester byproducts.

297 citations


Journal ArticleDOI
TL;DR: Both erythro and threo isomers of B-(3,3-dimethyl-1,2-dideuterio-1-butyl)-9-BBN were prepared through a hydroboration-deuteronolysis-hydroboration sequence employing first 9- BBN-H and then 9-BBn-D, or in reverse order, respectively, to demonstrate coupling rates with the exclusive reaction of 10 over 11 in competitive experiments.
Abstract: Both erythro and threo isomers of B-(3,3-dimethyl-1,2-dideuterio-1-butyl)-9-BBN (6) were prepared from 3,3-dimethyl-1-butyne (4) through a hydroboration−deuteronolysis−hydroboration sequence employing first 9-BBN-H and then 9-BBN-D, or in reverse order, respectively. Employing the Whitesides protocol, the stereochemistry of B → Pd alkyl group transfer in the Suzuki−Miyaura coupling of 6 to PhBr has been found to occur with complete retention of configuration with respect to carbon. For the coupling process, the Lewis acidity of the boron plays an important role with B-alkyl-9-BBN (10) forming [HO(R)-9-BBN]-1 (12) with the added base, in marked contrast to their B-alkyl-9-oxa-10-borabicyclo[3.3.2]decane counterparts (R-OBBD, 11) which do not. This behavior parallels their coupling rates with the exclusive reaction of 10 over 11 in competitive experiments. Five five possible roles were demonstrated for the added base in the coupling: (1) the formation of 12, (2) the hydrolysis of Ph(Ph3P)2PdBr (14) to prov...

297 citations


Journal ArticleDOI
Abstract: The reactivity of a new three carbon synthon, generated in situ from the reaction of 2,3-butadienoates or 2-butynoates with an appropriate phosphine as the catalyst, toward the electron-deficient imines is described. Triphenylphosphine-catalyzed reaction of methyl 2,3-butadienoate with N-sulfonylimines gave the single [3+2] cycloadduct in excellent yield; tributylphosphine-catalyzed reaction of methyl 2,3-butadienoate or 2-butynoate with N-tosylimines afforded the corresponding [3+2] cycloadduct as the major product along with a small amount of the three components adduct. Aliphatic N-tosylimines gave moderate yield for this reaction. In addition, a new phosphine-catalyzed cyclization reaction of dimethyl acetylenedicarboxylate with N-tosylimines is also described. A reaction mechanism is proposed. Further elaborations of the cycloaddition products and the synthesis of pentabromopseudilin using this method are exemplified.

283 citations


Journal ArticleDOI
TL;DR: In this paper, the reactivity of various onium salts derived from HOXt (X = A, B) was correlated with the structure of the reagents in question, and it was confirmed that the aza derivatives are more reactive than the parent benzotriazole derivatives in both activation and coupling.
Abstract: Peptide coupling methods derived from onium salts based on 1-hydroxybenzotriazole (HOBt) and 1-hydroxy-7-azabenzotriazole (HOAt) are becoming incorporated in synthetic strategies more frequently than the classical carbodiimide methods. We have correlated the reactivity of various onium salts derived from HOXt (X = A, B), with the structure of the reagents in question. Thus, we confirmed that the aza derivatives are more reactive than the parent benzotriazole derivatives in both activation and coupling. In addition, the activation step is determined by the structure of the carbon skeleton. Thus, pyrrolidino derivatives appear to be reagents of choice relative to the piperidino analogues or those derived from trialkylamines. Furthermore although phosphonium salts are slightly less reactive than the corresponding aminium/uronium salts, the former should be used for the activation of hindered species, since the latter may lead to the formation of guanidino derivatives.

260 citations


Journal ArticleDOI
TL;DR: A palladium-catalyzed α-arylation of amides was reported in this article, where the palladium catalyst was formed in situ from Pd(dba)2 (dba = trans,trans-dibenzylidene acetone).
Abstract: 2A palladium-catalyzed α-arylation of amides is reported. Intermolecular arylation of N,N-dimethylamides and lactams occurs using aryl halides, silylamide base, and a palladium catalyst. Intramolecular arylation of N-(2-halophenyl)amides occurs using alkoxide base and a palladium catalyst. The palladium catalyst was formed in situ from Pd(dba)2 (dba = trans,trans-dibenzylidene acetone) and BINAP (2,2‘-bis(diphenylphosphino)-1,1‘-binaphthalene). Although the intermolecular arylation of amides is less general than that reported previously for ketones, unfunctionalized and electron-rich aryl halides gave α-arylamides in 48−75% yield and N-methyl-α-phenylpyrrolidinone in 49% yield. These reactions provided the highest yields yet reported for regioselective amide arylations. Intramolecular amide arylation of 2-bromoanilides gave oxindoles in 52−82% yield. Mono- and disubstituted acetanilides gave 1,3-di- and 1,3,3-trisubstituted oxindoles. The use of dioxane, rather than THF, solvent was important for some of ...

258 citations




Journal ArticleDOI
TL;DR: Trimethylsilyl trifluoromethanesulfonate is an excellent catalyst for the acylation of alcohols with acid anhydrides and was used in this paper.
Abstract: Trimethylsilyl trifluoromethanesulfonate is an excellent catalyst for the acylation of alcohols with acid anhydrides. Highly functionalized primary, secondary, tertiary, and allylic alcohols, and phenols, were acylated cleanly and efficiently and in a fraction of the time used under the standard DMAP conditions.


Journal ArticleDOI
TL;DR: In this paper, it was shown that linear relationships exist between energetic, geometric, and magnetic criteria of aromaticity are invalid for any representative set of heteroaromatics in which the number of heteroatoms varies.
Abstract: Recent claims that linear relationships exist between energetic, geometric, and magnetic criteria of aromaticity are shown to be invalid for any representative set of heteroaromatics in which the number of heteroatoms varies.

Journal ArticleDOI
TL;DR: In this article, the carbonylative cross-coupling reaction of arylboronic acids with aryls electrophiles to yield unsymmetrical biaryl ketones was carried out in anisole at 80 °C in the presence of a palladium catalyst and a base.
Abstract: The carbonylative cross-coupling reaction of arylboronic acids with aryl electrophiles (ArI, ArBr, and ArOTf) to yield unsymmetrical biaryl ketones was carried out in anisole at 80 °C in the presence of a palladium catalyst and a base. The reaction selectively proceeded under an atmospheric pressure of carbon monoxide when PdCl2(PPh3)2 (3 mol %)/K2CO3 (3 equiv) were used for aryl iodides and PdCl2(dppf) (3 mol %)/K2CO3 (3 equiv)/KI (3 equiv) for the bromides or the triflates. The carbonylation of arylboronic acids with benzyl halides gave aryl benzyl ketones.

Journal ArticleDOI
TL;DR: In this article, a highly enantioselective and practical synthesis of the HIV-1 reverse transcriptase inhibitor efavirenz (1) is described, which proceeds in 62% overall yield in seven steps from 4-chloroaniline (6) in excellent chemical and optical purity.
Abstract: A highly enantioselective and practical synthesis of the HIV-1 reverse transcriptase inhibitor efavirenz (1) is described. The synthesis proceeds in 62% overall yield in seven steps from 4-chloroaniline (6) to give efavirenz (1) in excellent chemical and optical purity. A novel, enantioselective addition of Li-cyclopropyl acetylide (4a) to p-methoxybenzyl-protected ketoaniline 3a mediated by (1R,2S)-N-pyrrolidinylnorephedrine lithium alkoxide (5a) establishes the stereogenic center in the target with a remarkable level of stereocontrol.



Journal ArticleDOI
TL;DR: In this article, the use of TAS-F [tris(dimethylamino)sulfonium difluorotrimethylsilicate, (Me2N)3S+ F2SiMe3] for the deprotection of a range of silyl ethers and 2-(trimethylsilyl)ethyl carbamates and esters was reported.
Abstract: Numerous methods have been developed for the introduction and selective removal of silicon-containing protecting groups, which are used extensively in organic synthesis.2-4 Nevertheless, there remains a great need for the development of ever milder and more selective methods for silyl group deprotection for use with baseand/or acid-sensitive substrates. Herein, we report the use of TAS-F [tris(dimethylamino)sulfonium difluorotrimethylsilicate, (Me2N)3S+ F2SiMe3] for the deprotection of a range of silyl ethers and 2-(trimethylsilyl)ethyl carbamates and esters. Particularly striking are the TAS-F-mediated deprotections of the base-sensitive substrates 1, 3, 5, 11, and 13, which could not be deprotected cleanly or efficiently by using tetra-nbutylammonium fluoride (TBAF).

Journal ArticleDOI
TL;DR: In this article, a simple and efficient procedure for the rearrangement of substituted epoxides catalyzed by InCl3 has been developed, which provides a highly selective synthesis of substituted benzylic aldehydes and ketones.
Abstract: A simple and efficient procedure for the rearrangement of substituted epoxides catalyzed by InCl3 has been developed. Aryl-substituted epoxides isomerize with complete regioselectivity to form a single carbonyl compound via cleavage of the benzylic C−O bond. The reactions are simple, fast, and high yielding. This procedure is very mild compared to those catalyzed with BF3 and other Lewis acids and compatible with several acid-sensitive functionalities. This protocol provides a highly selective synthesis of substituted benzylic aldehydes and ketones. However, rearrangement of alkyl-substituted epoxides is not very selective.

Journal ArticleDOI
TL;DR: In this paper, the [2 + 2] dimer of fullerene C60 was achieved by the solid-state mechanochemical reaction of C60 with KCN by the use of a high-speed vibration milling (HSVM) technique.
Abstract: The bulk synthesis of the [2 + 2] dimer of fullerene C60 was achieved by the solid-state mechanochemical reaction of C60 with KCN by the use of a high-speed vibration milling (HSVM) technique. This reaction took place also by the use of potassium salts such as K2CO3 and CH3CO2K, metals such as Li, Na, K, Mg, Al, and Zn, and organic bases such as 4-(dimethylamino)- and 4-aminopyridine. Under optimum conditions, the reaction afforded only the dimer C120 and unchanged C60 in a ratio of about 3:7 (by weight) regardless of the reagent used. The dimer C120 was fully characterized by IR, UV−vis, 13C NMR, and TOF MS spectroscopies, cyclic voltammetry, and differential scanning calorimetry. Comparison of the IR and 13C NMR spectral data of C120 with those reported for all-carbon C60 polymers implied that the [2 + 2] dimer C120 represents the essential subunit of these polymers. The dimer C120 underwent facile dissociation into two C60 molecules by heat, HSVM treatment, exposure to room light, or electrochemical re...






Journal ArticleDOI
TL;DR: Czerneck et al. as discussed by the authors showed that substitution on the aromatic ring could have an adverse steric effect that would interfere with the planar geometry required for effective binding and thus reduce its affinity for the metal surface.
Abstract: Benzyl protection of a hydroxyl group is one of the most frequently used procedures in synthesis because of the mild conditions involved in its removal by catalytic hydrogenolysis.1-3 The synthesis of polyhydroxylated compounds often requires orthogonal protecting strategies to distinguish between hydroxyl groups. It would be highly desirable to develop a range of benzyl-type protecting groups with different reactivities that can be sequentially removed via catalytic hydrogenolysis. This requires a detailed understanding of the mechanism of the cleavage of the benzyl oxygen bond by the palladium hydrogen species. Recently, we have determined the amphipolar nature of the palladium hydrogen bond (modes a, Mδ+ Hδ-, or b, MδHδ+) in both homogeneous4 and heterogeneous5 hydrogenation of alkenes. This has led us to test whether the electronic properties of the aromatic group can influence the rate of cleavage, which should in turn guide the development of hydroxyl protecting groups with different reactivities. The results in Table 1 show that the rate of debenzylation can be dramatically affected by the electronic properties of the aromatic ring. The substitution of the electron-withdrawing trifluoromethyl group onto the aromatic ring severely retards debenzylation under 1 atm of hydrogen. In contrast, there is considerable acceleration by electrondonating substituents, which suggests that the benzylic carbon bears a partial positive charge in the transition state. The hydrogenolysis of benzyl alcohols carried out in acetic acid has shown that protonation of the hydroxyl group is essential for the cleavage of the carbon-oxygen bond.6 Under the neutral conditions in our study, the reaction may occur by protonation of the benzyl oxygen atom, through the operation of mode b, MδHδ+, to give a positively charged benzylic carbon. Alternativly, it is possible that palladium could act as a Lewis acid and coordinate to the benzyl oxygen atom to promote the same electron-deficient transition state (mode a, Mδ+ Hδ-). The large difference in reactivity within this range of substituted benzyl groups suggests that they can be sequentially deprotected, therefore proving useful in multistep synthesis. To test the synthetic application of these groups, competition experiments were conducted on model systems with two differently substituted benzyl groups attached to ethanediol (Scheme 1a). Surprisingly, the benzyl group was cleaved first in competition with any of the substituted benzyl groups. This phenomenon has been observed with the 4-methoxybenzyl group (PMB); however, no explanation was proposed.7,8 The results with the linker experiments (Scheme 1a) seem to contradict those obtained when only one benzyl group is involved (Table 1). Surface scientists have determined that the aromatic ring lies flat on the metal surface for optimal coordination.9,10 It is possible that substitution on the aromatic ring could have an adverse steric effect that would interfere with the planar geometry required for effective binding and thus reduce its affinity for the metal surface. The linker experiments show that the limited number of active sites on the palladium surface could lead to a competition for adsorption sites between substituted and unsubstituted benzyl groups. This may explain why the least substituted benzyl group, although not electronically favored, can still be preferentially cleaved. It is clear that for the rational design of selective benzyl type protecting groups both electronic factors and adsorption must be taken into account. For synthetic purposes, it would be desirable to find a more labile group than the benzyl group for protection of the hydroxyl functionality. We anticipated that the 2-naphthylmethyl (NAP) group would fulfill these criteria: it is electron rich and should have a (1) Greene, T. W.; Wuts, P. G. M. In Protective Groups in Organic Synthesis; John Wiley & Sons, Inc.: New York, 1991. (2) (a) Czernecki, S.; Georgoulis, C.; Provelenghiou, C. Tetrahedron Lett. 1976, 3535. (b) Iverson T.; Bundle K. R. J. Chem. Soc., Chem. Commun., 1981, 1240. (3) Czech, B. P.; Bartsch, R. A. J. Org. Chem. 1984, 49, 4076. (4) Yu, J.; Spencer, J. B. J. Am. Chem. Soc. 1997, 119, 5257. (5) Yu, J.; Spencer, J. B. J. Org. Chem. 1997, 62, 8618. (6) Kieboom, A. P. G.; De Kreuk, J. F.; Van Berkum, H. J. Catal. 1971, 20, 58. (7) Srikrishna, A.; Viswajanani, J. A.; Sattigeri, J. A.; Vijaykumar, D. J. Org. Chem. 1995, 60, 5961. (8) Sajiki, H.; Kuno, H.; Hirota, K. Tetrahedron Lett. 1997, 38, 399. (9) Lin, R. F.; Koestner, R. J.; Van Hove, M. A.; Somorjai, G. A. Surf. Sci. 1983, 161. (10) Held, G.; Bessent, M. P.; Titmuss, S.; King, D. A. J. Chem. Phys. 1996, 11305. Table 1a


Journal ArticleDOI
TL;DR: The total synthesis of (+)-discodermolide is described in this article, which involves assemblage of three key stereotriad subunits through addition of nonracemic allenyltin, -indium, and -zinc reagents to (S)-3-silyloxy-2-methylpropanal derivatives, followed by reduction of the resulting anti,syn- or syn,synhomopropargylic alcohol adducts to the (E)-homoallylic alcohols and subsequent Sharpless epoxidation.
Abstract: The total synthesis of (+)-discodermolide is described. The approach involves assemblage of three key stereotriad subunits through addition of nonracemic allenyltin, -indium, and -zinc reagents to (S)-3-silyloxy-2-methylpropanal derivatives, followed by reduction of the resulting anti,syn- or syn,syn-homopropargylic alcohol adducts to the (E)-homoallylic alcohols and subsequent Sharpless epoxidation. Addition of methyl cuprate reagents or Red-Al to the resultant epoxy alcohols yielded the key precursors, alkyne 4, aldehyde 9, and alcohol 24. Addition of alkyne 4 (as the lithio species 10) to aldehyde 9 afforded the propargylic alcohol 11 as the major stereoisomer. Lindlar hydrogenation and installation of appropriate protecting groups led to aldehyde 17. This was converted to the (Z)-vinylic iodide 18 upon treatment with α-iodoethylidene triphenylphosphorane. Suzuki coupling of this vinylic iodide with a boranate derived from iodide 25 led to the coupled product 27 with the complete carbon backbone of (+)...