Rhodium-Mediated Stoichiometric Synthesis of Mono-, Bi-, and Bis-1,2-Azaborinines: 1-Rhoda-3,2-azaboroles as Reactive Precursors

A series of highly substituted 1,2-azaborinines, including a phenylene-bridged bis-1,2-azaborinine, was synthesized from the reaction of 1,2-azaborete rhodium complexes with variously substituted alkynes. 1-Rhoda-3,2-azaborole complexes, which are accessible by phosphine addition to the corresponding 1,2-azaborete complexes, were also found to be suitable precursors for the synthesis of 1,2-azaborinines and readily reacted with alkynyl-substituted 1,2-azaborinines to generate new regioisomers of bi-1,2-azaborinines, which feature directly connected aromatic rings. Their molecular structures, which can be viewed as boron-nitrogen isosteres of biphenyls, show nearly perpendicular 1,2-azaborinine rings. The new method using rhodacycles instead of 1,2-azaborete complexes as precursors is shown to be more effective, allowing the synthesis of a wider range of 1,2-azaborinines.     

Reaction of 4-aryl-3-thiosemicarbazides with carbon disulfide: A facile synthesis of 2,3-dihydrothiazoles and their fused derivatives

The reaction of 3-aryl-3-thiosemicarbazides 1a-d with carbon disulfide in alkaline medium affords the non-isolable sulfide salts 2a-d. The latter undergo in situ heterocyclization with some α-halogenated compounds, e.g., 3a,b and 13, to afford polyfunctionally substituted 2,3-dihydrothiazoles 4a-e and thiazolidine 14, respectively, which, in turn, could be annelated into fused heterocyclic systems. Chemical and spectroscopic evidence for the new compounds are described. © 1997 John Wiley & Sons, Inc.     

钯催化四氟硼酸芳香重氮盐的乙氧基羰基化反应

取代苯甲酸乙酯;制备;钯催化四氟硼酸芳香重氮盐的乙氧基羰基化反应     

Hetaryl-substituted phosphonium-iodonium ylides in synthesis of heterocycles

A series of hitherto unknown hetaryl-substituted (in phosphonium part) phosphonium-iodonium ylides were synthesized. The reaction of these mixed phosphonium-iodonium ylides with acetylenes opens a way to new furyl annelated phosphinolines or unusually substituted phosphininofurans.     

Sequential silylcarbocyclization/silicon-based cross-coupling reactions

A sequential rhodium-catalyzed silylcarbocyclization of enynes parlayed with a palladium-catalyzed, silicon-based cross-coupling reaction has been developed for the synthesis of highly substituted cyclopentanes. 1,6-Enynes reacted with benzyldimethylsilane in the presence of rhodium catalysts to afford five-membered rings bearing a (Z)-alkylidenylbenzylsilyl group. A variety of substitution patterns and heteroatom substituents were compatible. The silylcarbocyclization in which an unsaturated ester participated was also achieved. The resulting alkylidenylsilanes underwent palladium-catalyzed cross-coupling using tetra-n-butylammonium fluoride. This cross-coupling reaction displayed a broad substrate scope. A wide variety of substitution patterns, electronic properties, and heteroatoms were compatible. All of the cross-coupling reactions proceeded in high yields under very mild conditions and with complete retention of double bond configuration, resulting in densely functionalized 3-(Z)-benzylidenecyclopentanes and heterocycles.     

First synthesis of pyrrolothiadiazinones. An alternative core ring for xanthine based structures

The first synthesis of pyrrolothiadiazine core ring bearing substituents at positions 1, 3 and 6 is described, using a straightforward synthesis from diversely substituted 5-methylthiadiazines. These structures are of interest not only because they can be considered as useful building blocks but also because they can potentially be used as alternative core rings for biologically important molecules bearing xanthine as a central core.     

Stereoselective Synthesis of Unsaturated and Functionalized l-NHBoc Amino Acids, Using Wittig Reaction under Mild Phase-Transfer Conditions

The stereoselective synthesis of a new amino acid phosphonium salt was described by quaternization of melting triphenylphosphine with the γ-iodo NHBoc-amino ester, derived from l-aspartic acid. The deprotection of the carboxylic acid function to afford the phosphonium salt with a free carboxylic acid group was achieved by a palladium-catalyzed desallylation reaction. This phosphonium salt was used in the Wittig reaction with aromatic or aliphatic aldehydes and trifluoroacetophenone, under solid-liquid phase-transfer conditions in chlorobenzene and in the presence of K(3)PO(4) as weak base, to afford the corresponding unsaturated amino acids without racemization. Thus, the reaction with substituted aldehydes allows to graft various functionalized groups on the lateral chain of the amino acid, such as trifluoromethyl, cyano, nitro, ferrocenyl, boronato, or azido. In addition, the reaction of the amino acid Wittig reagent with α,β-unsaturated aldehydes leads to amino acids bearing a diene on the lateral chain. Finally, this amino acid phosphonium salt appears to be a new powerful tool for the preparation of unsaturated and non-proteinogenic α-amino acids, directly usable for the synthesis of customized peptides.     

Cascade approach to substituted 6-aryl-phenanthridines from aromatic aldehydes, anilines, and benzenediazonium-2-carboxylate

Aromatic aldehydes reacted with anilines and benzenediazonium-2-carboxylate to afford 6-aryl-phenanthridines. The reaction furnishes a rapid and direct construction of substituted phenanthridine rings from readily available starting materials via a one-pot cascade process.     

Facile synthesis of highly substituted 3-aminofurans from thiazolium salts, aldehydes, and dimethyl acetylenedicarboxylate

[reaction: see text] A facile preparation of 3-aminofuran derivatives via multicomponent reactions of thiazole carbenes, aldehydes, and dimethyl acetylenedicarboxylate (DMAD) is reported. In this process, the thiazole carbenes, generated in situ from thiazolium salts, reacted with aldehydes and DMAD at -78 to 0 degree C in CH(2)Cl(2) to afford the substituted furans in moderate to good yields. Eight substituted thiazolium salts were employed as carbene precursors in the reaction. Besides aryl aldehydes, alpha,beta-unsaturated aldehydes, aliphatic aldehydes, and arenedial were also investigated and found to be applicable to this reaction.     

Palladium(0)-catalyzed synthesis of medium-sized heterocycles by using bromoallenes as an allyl dication equivalent

We have developed a highly regio- and stereoselective synthesis of medium-sized heterocycles containing one or two heteroatoms via cyclization of bromoallenes bearing an oxygen, nitrogen, or carbon nucleophilic functionality in the presence of a palladium(0) catalyst and alcohol. In this reaction, bromoallenes act as an allyl dication equivalent, and the intramolecular nucleophilic attack takes place exclusively at the central carbon atom of the allene moiety. Interestingly, bromoallenes having a carbon nucleophile with a five-atom tether afford eight-membered rings with trans-configuration, while those having an oxygen or a nitrogen nucleophile give the corresponding cis-rings selectively. This is the first example that demonstrates the synthesis of medium-sized rings via cyclization of bromoallenes, and this reaction provides a very useful method for a catalytic synthesis of seven- and eight-membered heterocycles without using high dilution conditions.     

Asymmetric synthesis of unusual fused tricyclic beta-lactam structures via aza-cycloadditions/ring closing metathesis

Conveniently substituted bis-beta-lactams, pyrrolidinyl-beta-lactams, and piperidinyl-beta-lactams undergo ring-closing methatesis using Grubbs' carbene, Cl(2)(Cy(3)P)(2)Ru=CHPh, to give medium-sized rings fused to bis-2-azetidinone, pyrrolidinyl-2-azetidinone, or piperidinyl-2-azetidinone systems. The diolefinic cyclization precursors can be obtained from optically pure 4-oxoazetidine-2-carbaldehydes bearing an extra alkene tether at position 1 or 3 of the beta-lactam ring via [2 + 2] cycloaddition of imino 2-azetidinones, N-metalated azometine ylide [3 + 2] cycloaddition, and subsequent N-acylation of the pyrrolidinyl nitrogen atom, or through aza-Diels-Alder cycloaddition of 2-azetidinone-tethered imines. Under standard reaction conditions, the combination of cycloaddition reactions of 2-azetidinone-tethered imines with ring-closing methatesis offers an asymmetric entry to a variety of unusual fused tricyclic 2-azetidinones bearing two bridgehead nitrogen atoms.     

Visible‐Light‐Induced [4+2] Annulation of Thiophenes and Alkynes to Construct Benzene Rings

The [4+2] annulation represents an elegant and versatile synthetic protocol for the construction of benzene rings. Herein, a strategy for visible‐light induced [4+2] annulation of thiophenes and alkynes, to afford benzene rings, is presented. Under simple and mild reaction conditions, the ready availability and structural diversity of thiophenes and alkynes permit the facile synthesis of several substituted aromatic rings. Valuable drugs and amino acids are also well tolerated. Moreover, DFT calculations explain the high regioselectivity of the reaction.     

Synthesis of fluoren-9-ones by the palladium-catalyzed cyclocarbonylation of o-halobiaryls

The synthesis of various substituted fluoren-9-ones has been accomplished by the palladium-catalyzed cyclocarbonylation of o-halobiaryls. The cyclocarbonylation of 4'-substituted 2-iodobiphenyls produces very high yields of 2-substituted fluoren-9-ones bearing either electron-donating or electron-withdrawing substituents. 3'-Substituted 2-iodobiphenyls afford 3-substituted fluoren-9-ones in excellent yields with good regioselectivity. This chemistry has been successfully extended to polycyclic fluorenones and fluorenones containing fused isoquinoline, indole, pyrrole, thiophene, benzothiophene, and benzofuran rings.     

Application of Suzuki–Miyaura and Buchwald–Hartwig Cross‐coupling Reactions to the Preparation of Substituted 1,2,4‐Benzotriazine 1‐Oxides Related to the Antitumor Agent Tirapazamine

Many 1,2,4‐benzotriazine 1,4‐dioxides display the ability to selectively kill the oxygen‐poor cells found in solid tumors. As a result, there is a desire for synthetic routes that afford access to substituted 1,2,4‐benzotriazine 1‐oxides that can be used as direct precursors in the synthesis of 1,2,4‐benzotriazine 1,4‐dioxides. Here we describe the use of Suzuki–Miyaura and Buchwald–Hartwig cross‐coupling reactions for the construction of various 1,2,4‐benzotriazine 1‐oxide analogs bearing substituents at the 3‐position, 6‐position, and 7‐position.     

A concise synthesis of novel naphtho[a]carbazoles and benzo[c]carbazoles

Starting from simple indole precursors the synthesis of naphtho[a]carbazoles and benzo[c]carbazoles is described. Key steps include the use of the Suzuki-Miyaura reaction to afford 2- or 3-aryl substituted indoles, as well as a potassium t-butoxide and light assisted aromatic ring-forming reaction.     

The directing effect of annelated rings in aromatic systems—XI : Bromination of bicyclic phenols with heterocyclic annelated rings

Bicyclic phenols of type 1 with annelated rings containing a N or an O heteroatom (X = N or O) as well as the ring opened analogs have been brominated and the product distribution determined. The results indicate that while most annelated rings have a directing effect to the ar-β position of the molecule, a 6-membered annelated ring is an exception and it facilitates substitution in the ar-α position.     

Development of a one-pot asymmetric azaelectrocyclization protocol: synthesis of chiral 2,4-disubstituted 1,2,5,6-tetrahydropyridines

[reaction: see text] A one-pot procedure for tetracyclic chiral aminoacetals, the useful precursors for substituted piperidine synthesis, has been established via Stille-Migita coupling, 6pi-azaelectrocyclization, and aminoacetal formation from readily prepared vinylstannanes, vinyliodides, and cis-aminoindanol derivatives. Based on the method, chiral 2,4-disubstituted 1,2,5,6-tetrahydropyridines, bearing a variety of aromatic substituents at the C-2 position, have been prepared.     

Palladium‐Catalyzed Amination of Aryl Sulfides with Anilines

A combination of a palladium–NHC catalyst and potassium hexamethyldisilazide enables the amination of aryl sulfides with anilines to afford a wide variety of diarylamines. The reaction conditions are versatile enough for the reaction of even bulky ortho‐substituted aryl sulfides. This amination can be applied to the modular synthesis of N‐aryl carbazoles from the corresponding ortho‐bromothioanisoles. As aryl sulfoxides undergo extended Pummerer reactions to afford ortho‐substituted aryl sulfides, the Pummerer products are thus useful substrates for the amination to culminate in efficient syntheses of a 2‐anilinobenzothiophene and an indole as proof‐of‐principle of the utility of the extended Pummerer reaction/amination cascade.     

Development of an asymmetric trimethylenemethane cycloaddition reaction: application in the enantioselective synthesis of highly substituted carbocycles

A protocol for the enantioselective [3+2] cycloaddition of trimethylenemethane (TMM) with electron-deficient olefins has been developed. The synthesis of novel phosphoramidite ligands was critical in this effort, and the preparation and reactivity of these ligands is detailed. The evolution of the ligand design, commencing with acyclic amine-derived phosphoramidites and leading to cyclic pyrrolidine and azetidine structures, is discussed. The conditions developed to effect an asymmetric TMM reaction using 2-trimethylsilylmethyl allyl acetate were shown to be tolerant of a wide variety of alkene acceptors, providing the desired methylenecyclopentanes with high levels of enantioselectivity. The donor scope was also explored, and substituted systems were tolerated, including one bearing a nitrile moiety. These donors were reactive with unsaturated acylpyrroles, giving the product cyclopentane rings bearing three stereocenters in high enantioselectivity and complete diastereoselectivity.     

Concise preparation of 2,2-difluorohomopropargyl carbonyl derivatives. Application to the synthesis of 4,4-difluoroisoquinolinone congeners

A scalable synthesis of 2,2-difluorohomopropargyl esters was achieved using a magnesium-promoted Barbier reaction of substituted difluoropropargyl bromides with alkyl chloroformates. These 2,2-difluorohomopropargyl esters were effective precursors in the synthesis of homopropargylic amides-by aminolysis using AlMe3, as well as of ketones-through the reaction of the corresponding Weinreb amides with Grignard reagents. Ring closing metathesis using difluorinated 1,7-enyne carbonyl compounds furnished six-membered diene products, which were used as susbstrates in a Diels-Alder reaction to afford 4,4-difluoroisoquinolin-3-ones. The [2 + 2 + 2] cycloaddition of alkynes with fluorinated 1,7-diyne amides gave 4,4-difluoro-1,4-dihydro-3(2H)-isoquinolinone derivatives regioselectively.