Palladium-catalyzed highly regio- and stereoselective synthesis of (1E)- or (1Z)-1,2-dihalo-1,4-dienes via haloallylation of alkynyl halides

A highly efficient and selective synthesis of (1E)- or (1Z)-1,2-dihalo-1,4-dienes via Pd-catalyzed coupling of haloalkynes and allylic halides is described. The (1E)-1,2-dihalo-1,4-dienes were generated in good yields with excellent stereoselectivities (1E/1Z up to >98/2), while (1Z)-1,2-dihalo-1,4-dienes were produced in excellent yields and stereoselectivities (1Z/1E up to >98/2) by simply adding stoichiometric lithium halides.     

A novel titanium tetrahalide-mediated carbon-carbon bond-forming reaction: regioselective synthesis of substituted (E,Z)-1,5-dihalo-1,4-dienes

Reactions of aldehydes with 2 equiv of alkyne in the presence of TiX(4) (X = Cl, Br) regioselectively generated 1,5-dihalo-1,4-dienes in moderate to good yields with high (E,Z)-stereoselectivity. [reaction: see text]     

Domino N-H/C-H bond activation: copper-catalyzed synthesis of nitrogen-bridgehead heterocycles using azoles and 1,4-dihalo-1,3-dienes

Copper-catalyzed tandem coupling of 1,4-dihalo-1,3-dienes with azoles via an N-H bond and its adjacent C-H bond activation has been described. The reaction exhibits good regioselectivity when unsymmetrical 1,4-dihalo-1,3-diene is employed. This method provided a novel route to the synthesis of nitrogen-bridgehead azolopyridine derivatives.     

Preparation of partially substituted 1-halo- and 1,4-dihalo-1,3-dienes via reagent-controlled desilylation of halogenated 1,3-dienes

Depending on the desilylation reagents used, 1-halo-1,4-bis(trimethylsilyl)-1,3-butadienes afforded either 1-halo-1-trimethylsilyl-1,3-butadienes or 1-halo-4-trimethylsilyl-1,3-butadienes in excellent yields with excellent selectivity, respectively, when treated with CF3COOH or with NaOMe. These monosilylated 1,3-butadiene products could be further desilylated to generate their corresponding halobutadienes via the above reagent-controlled desilylation reaction. When 1,4-dihalo-1,4-bis(trimethylsilyl)-1,3-dienes were treated with MeONa/MeOH at room temperature, desilylation of both of the two trimethylsilyl groups took place to afford their corresponding 1,4-dihalo-1,3-dienes in excellent yields. The commonly used desilylation reagent CF3COOH did not work for these dihalobutadienes.     

Fe(III) halides as effective catalysts in carbon-carbon bond formation: synthesis of 1,5-dihalo-1,4-dienes, alpha,beta-unsaturated ketones, and cyclic ethers

Iron(III) halides have proven to be excellent catalysts in the coupling of acetylenes and aldehydes. When terminal acetylenes were used the main products obtained were 1,5-dihalo-1,4-dienes with (E,Z)-stereochemistry contaminated in some cases with (E)-alpha,beta-unsaturated ketones. The former carbonyl derivatives were the sole products isolated when nonterminal aromatic alkynes were used. When homopropargylic alcohols were used, a Prins-type cyclization occurred yielding 2-alkyl-4-halo-5,6-dihydro-2H-pyrans. In addition, anhydrous ferric halides are also shown to be excellent catalysts for the standard Prins cyclization with homoallylic alcohols. Isolation of an intermediate acetal, calculations, and alkyne hydration studies provide substantiation of a proposed mechanism.     

Diverse reactions of 1,4-dilithio-1,3-dienes with nitriles: facile access to tricyclic Delta1-bipyrrolines, multiply substituted pyridines, siloles, and (Z,Z)-dienylsilanes by tuning of substituents on the butadienyl skeleton

Addition cyclization of 1,2,3,4-tetrasubstituted 1,4-dilithio-1,3-dienes (Type I) with four equivalents of various aromatic nitriles in the presence of hexamethylphosphoramide (HMPA) gives exclusively fully substituted pyridines in moderate to good yields. Similarly, trisubstituted pyridines can be prepared by the reaction of 2,3-dialkyl- or diaryl-substituted 1,4-dilithio-1,3-dienes (Type II) with nitriles. However, five- or six-membered-ring fused 2,3-disubstituted 1,4-dilithio-1,3-dienes (Type III) reacted with various aromatic and aliphatic nitriles without alpha-hydrogen atoms to afford tricyclic Delta1-bipyrrolines in high yields. The reaction of six-membered-ring fused 2,3-disubstituted 1,4-dilithio-1,3-diene (Type III) with 2-cyanopyridine afforded the corresponding pyridine, and no tricyclic Delta1-bipyrroline was observed. Seven-membered-ring fused dilithiodienes reacted with PhCN or trimethylacetonitrile to afford the corresponding pyridines in good yield. When 1,2,3,4-tetrasubstituted dilithio reagents (Type I) were treated with Me3SiCN, a tandem silylation/intramolecular substitution process readily occurred to yield siloles, whereas the reaction of 2,3-disubstituted dilithio reagents (Types II and III) with Me3SiCN gave rise to (Z,Z)-dienylsilanes with high stereoselectivity. These results revealed that the formation of tricyclic Delta1-bipyrrolines, pyridines, siloles, and (Z,Z)-dienylsilanes are strongly dependent on the substitution patterns of the dilithio butadienes and the nature of the nitriles employed.     

Au-catalyzed synthesis of (1Z,3E)-2-pivaloxy-1,3-dienes from propargylic pivalates

Propargylic pivalates with electronically unbiased internal alkynes are selectively transformed into (1Z,3E)-2-pivaloxy-1,3-dienes containing various functionalities. The unusual selectivity of 1,2-acyloxy migration over the structurally preferred 3,3-rearrangement is realized. This reaction is highly stereoselective and offers rapid access to dienes for one-pot intra-/intermolecular Diels-Alder reactions either under thermal conditions or with Lewis acid catalysis.     

A copper (I or II)/diethylphosphite catalytic system for base-free additive dimerization of alkynes

Copper (I) or copper (II) salts and oxides promote regioselective head-to-head additive dimerization of aromatic and aliphatic terminal alkynes in the presence a catalytic amount of diethylphosphite. The reaction proceeds under ambient conditions without any added base with the formation of 1,4-disubstituted 1,3-enynes with the E isomer as major product in good to excellent yields. A plausible mechanism for additive dimerization of terminal alkynes is proposed.     

Rare-earth silylamide-catalyzed selective dimerization of terminal alkynes and subsequent hydrophosphination in one pot

[reaction: see text] Rare-earth silylamides, Ln[N(SiMe3)2]3 (Ln = Y, La, Sm), catalyzed regio- and stereoselective dimerization of terminal alkynes in the presence of amine additives to give conjugated enynes in high yields. The additives played a crucial role to depress the oligomerization and to control the regio- and stereochemistry of the dimerization. Thus, the selectivity for (Z)-head-to-head enynes was increased in the order of tertiary < secondary < primary amine additives. On the other hand, the reversed order was observed for the formation of head-to-tail dimers. When alpha,omega-diynes were subjected to the dimerization, very novel cyclic bisenyne compounds were given through double-dimerization in satisfactory yields. In addition, an application of the system allowed subsequent hydrophosphination of the enynes generated in situ with diphenylphosphine, giving rise to 1-phosphinyl-1,3-dienes as the sole products in excellent yields after oxidative workup.     

Cu-catalyzed tandem C-N bond formation for the synthesis of pyrroles and heteroarylpyrroles

A highly efficient Cu-catalyzed tandem C-N bond-forming reaction of 1,4-dihalo-1,3-dienes has been developed. The transformation allows the synthesis of pyrroles and heteroarylpyrroles with a wide variety of functional groups and substitution patterns from readily available precursors.     

Synthesis of stereo-defined 1,1,4,4-tetrahalo- and 1,1,4,4-mixed-tetrahalo-1,3-butadienes

Stereo-defined 1,1,4,4-tetrahalo- and 1,1,4,4-mixed-tetrahalo-1,3-butadienes were obtained in excellent yields via desilylation-halogenation of their corresponding 1,4-bis(trimethylsilyl)-1,4-dihalo-1,3-dienes, which could be readily prepared from the zirconocene-mediated high-yield and high-regioselective cyclo-dimerization of 1-trimethylsilyl-1-alkynes followed by halogenation. These poly-functionalized gem-dihalodienes are potentially useful building blocks.     

Palladium(II)-catalyzed S(N)2' reactions of alpha-allenic acetates. Stereoconvergent synthesis of (Z,E)-2-bromo-1,3-dienes.

The reaction of acetylated alpha-allenic alcohols with LiBr in the presence of 1.5 mol % of Pd(OAc)(2) provides easy access to substituted (Z,E)-2-bromo-1,3-dienes in good yields with excellent diastereoselectivity. Both secondary and tertiary acetates as well as terminal and nonterminal allenes were studied to investigate the scope and the limitations of the reaction. A mechanism is proposed to clarify how a diastereomeric mixture of the starting compound is transformed into a single diastereomer of the product.     

3,3,3-trichloropropyl-1-triphenylphosphorane: a reagent for the synthesis of (Z)-1,3-enynes, (Z,Z)-1-chloro-1,3-dienes, and 1,3-diynes

3,3,3-Trichloropropyl-1-triphenylphosphonium chloride is conveniently prepared from 2-chloroethanol, triphenylphosphine, and trichloroacetic acid. Deprotonation of this reagent generates 3,3,3-trichloropropyl-1-triphenylphosphorane, which reacts with aldehydes to give trichloromethylated (Z)-olefins, which are useful for the synthesis of (Z)-1,3-enynes, (Z,Z)-1-chloro-1,3-dienes, and 1,3-diynes in high yields and stereospecificities.     

Synthesis, structure, and reactivity of novel 3,4-diphosphacyclobutenes bearing silyl groups

[reaction: see text] Copper-mediated homocoupling of sterically hindered 2-(2,4,6-tri-tert-butylphenyl)-1-trialkylsilyl-2-phosphaethenyllithiums afforded 1,2-bis(trialkylsilyl)-3,4-diphosphacyclobutenes (1,2-dihydrodiphosphetenes) through a formal electrocyclic [2+2] cyclization in the P=C-C=P skeleton as well as 2-trimethylsilyl-1,4-diphosphabuta-1,3-diene. Reduction of 1,2-bis(trimethylsilyl)-3,4-diphosphacyclobutenes followed by quenching with electrophiles afforded ring-opened products, (E)-1,2-bis(phosphino)-1,2-bis(trimethylsilyl)ethene and (Z)-2,3-bis(trimethylsilyl)-1,4-diphosphabut-1-ene. The structures of the ring-opened products indicated E/Z isomerization around the C=C bond after P-P bond cleavage of 5, and the isomerization of the P-C=C skeleton. Ring opening of 1,2-bis(trimethylsilyl)-3,4-diphosphacyclobutenes affording (E,E)- and (Z,Z)-1,4-diphosphabuta-1,3-dienes was observed upon desilylation.     

Formation of stable enols from 1,4-dilithio-1,3-dienes and acid chlorides by a de-aromatization/Michael addition/re-aromatization domino process

Stable enols were synthesized from the reaction of (1Z,3Z)-1,4-dilithio-1,3-dienes with acid chlorides and structurally characterized by single-crystal X-ray analysis. These stable enols were formed by a novel de-aromatization/Michael addition/re-aromatization domino process.     

N,N-dihalophosphoramides-XV: The addition of diethyl N,N-dichlorophosphoroamidate (DCPA) to conjugated 1,3-dienes

The addition of DCPA to several conjugated 1,3-dienes has been studied. The reaction was found to proceed in dichloromethane and was spontaneously or photolytically initiated depending on the structure of the dienes. N-chloro adducts, formed upon addition, could be reduced “in situ” with sodium sulphite solution to give the corresponding diethyl N-(chloroalkenyl)posphoroamidates. Addition of DCPA to terminal double bond 1,3-dienes (butadiene, isoprene and 2,3-dimethyl-1,3-butadiene) leads regiospecifically to (E)-1,4-adducts. Similarly, 1,4-addition is also observed for 1,3-cyclohexadiene. Reaction of DCPA with nonterminal double bond 1,3-dienes (trans-piperylene, 4-methyl-1,3-pentadiene, 2,5-dimethyl-2,4-hexadiene and 1,4-diphenyl-1,3-butadiene) usually affords a mixture of adducts. Spectral data and chemical transformations pertinent to the proof of structure of DCPA addition products are presented. A possible mechanism for the addition is discussed.     

Novel Z-selective head-to-head dimerization of terminal alkynes catalyzed by lanthanide half-metallocene complexes

Various terminal alkynes have been cleanly dimerized into the corresponding head-to-head (Z)-enynes by use of the half-metallocene lutetium alkyl complexes Me2Si(C5Me4)(NAr)Lu(CH2SiMe3)(THF) (Ar = Ph, C6H3Me2-2,6, C6H2Me3-2,4,6) as catalysts. Aromatic C-Cl, C-Br, and C-I bonds, which are known to be extremely susceptible to reductive cleavage by transition metals, survived in the present reactions. The corresponding dimeric alkynide species [Me2Si(C5Me4)(NAr)Lu(mu-CCR)]2 are thought to be the true catalysts, some of which have been isolated and structurally characterized. These alkynide species were thermally stable and soluble at the reaction temperatures (80-110 degrees C), but they precipitated upon cooling to room temperature after completion of the reaction. Therefore, this catalyst system works homogeneously but can be separated and reused, thus constituting the first example of a recyclable catalyst system for the dimerization of terminal alkynes and also the first example of (Z)-selective head-to-head dimerization of aromatic terminal alkynes.     

1,3-Cycloaddition von alkinen an hetero-1,3-diene 1-aminopyrrole aus 1,2-diazabuta-1,3-dienen und 1-diethylaminopropin

1-Aminopyrroles (4) are obtained by reaction of 1,2-diazabuta-1,3-dienes (1) and ynamines (2). This reaction represents one of the very rare examples of 1,3-cycloaddition processes of alkynes and hetero-1,3-dienes.     

A new halopropargylation of alkynes promoted by boron trihalides. highly stereo- and regioselective syntheses of substituted (Z)-1-halo-1,4-enyne derivatives

[reaction: see text] A new halopropargylation of alkynes promoted by boron trihalides has been developed. Reactions of (Z)-2-halo-1-vinylboron dihalides (generated in situ via reaction of alkynes with boron trihalides) with lithium propargyloxides in CH(2)Cl(2) at room temperature produce the corresponding (Z)-1-halo-1,4-enynes in modest to good yields.     

A concise synthesis of substituted stilbenes and styrenes from propargylic phosphonium salts by a cobalt-catalyzed Diels-Alder/Wittig olefination reaction sequence

The cobalt(I)-catalyzed Diels-Alder reaction of propargylic phosphonium salts and longer chained alkyne-functionalized phosphonium salts with 1,3-dienes led to dihydroaromatic phosphonium salt intermediates which were directly used in a one-pot Wittig-type olefination reaction with aldehydes. Subsequent oxidation led to styrene- and stilbene-type products under formation of three new carbon-carbon bonds in a single synthetical step starting from three variable starting materials. The E/Z stereoselectivities of the products revealed that the dihydroaromatic phosphonium ylides behave as semistabilized ylides giving predominantly the E-configured products. The application of unsymmetrical 1,3-dienes as well as internal phosphonium functionalized alkynes is also described.