Adducts 3a Research Articles

Monomeric 1‐Borylimidazoles: Syntheses, Structure and Reactivity of 1‐[Bis(diisopropylamino)boryl]imidazoles

AbstractReactions of chlorobis(diisopropylamino)borane with 1‐(trimethylsilyl)imidazole and 4,5‐dimethyl‐1‐(trimethylsilyl)imidazole lead to the monomeric 1‐borylimidazoles 3a and 3b. Treatment of 3a with the Lewis acid BF3 results in the quantitative formation of the corresponding trifluoroborane adduct 4a. In contrast, 3a reacts with the stronger Lewis acids BCl3, BBr3, and BI3 to partially substitute the diisopropylamino groups and form the corresponding adducts, depending on the Lewis acidity of the reagent; 3a forms, with Mo(CO)5thf and Cp′Mn(CO)2thf, the complexes 3‐[(OC)5Mo]3a (8) and 3‐[(OC)2Cp′Mn]3a (6). The product compositions agree with spectroscopic and analytical data and with X‐ray structure analyses of 3a, 3b, 4a, 8, and 9. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

An Improved Procedure for the Asymmetric Aldol Reaction of the Titanium Enolate of an N3‐Propionyl‐3,4,5,6‐tetrahydro‐2H‐1,3,4‐oxadiazin‐2‐one.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Photo aldol reactions with 5-methoxyoxazoles: Highly regio- and diastereoselective synthesis of α-amino β-hydroxy carboxylic acid derivatives

A versatile route to derivatives of α-amino β-hydroxy carboxylic acids, either with tertiary (from a corresponding glycine equivalent) or a quaternary α-carbon center is described. The key reaction is the cycloaddition of electronically excited carbonyl compounds (aromatic and aliphatic aldehydes, respectively) to oxazoles. To make the products hydrolytically more labile, a methoxy substituent at position C-5 was introduced leading to the formation of cycloadducts with an orthoester substructure. The photocycloaddition, either with triplet excited (aromatic) carbonyls or with singlet excited (aliphatic) carbonyls, led to the formation of mixtures of endo- and exo-diastereoisomers with moderate to very high exo-selectivities. The 4-unsubstituted 5-methoxyoxazole 1 (glycine equivalent) gave the [2 + 2]-adducts 3a–3f with aldehydes 2a–2f in high yields and excellent diastereoselectivities. Hydrolysis of these compounds resulted in the α-amino β-hydroxy esters 4a–4f with preferred erythro (S*,S*) configuration. As an extension of this process, 4-alkylated 5-methoxyoxazoles 5a–5f were applied as alkene components and the corresponding cycloadducts with benzaldehyde 6a–6f were obtained. Again, the exo-diastereoisomers were formed as the major products in diastereoselectivities from 73:27 (exo:endo) up to >95:5. Hydrolysis of these adducts resulted in the formation of α-amino β-hydroxy esters 7a–7f with like (S*,S*) configuration of the major diastereoisomers.Key words: photo aldol reaction, oxazoles, oxetanes, photocycloaddition, amino acids, hydroxy acids.

Chiral 1,8-bis( tert-butylphenylphosphino)naphthalene oxides and sulfides: resolution and structures

Chiral racemic 1,8-bis( tert-butylphenylphosphino)naphthalene oxide ( 2a) was resolved into enantiomers by fractional crystallization of its diastereomeric adducts 3a with (+)-(2 S,3 S)-di- O-benzoyl tartaric acid (DBTA), followed by neutralization. Racemic 1,8-bis( tert-butylphenylphosphino)naphthalene ( 1a) was oxidized with sulfur to two isomers of 1,8-bis( tert-butylphenyl-phosphino)naphthalene monosulfide, rac- 4a and rac- 4a′, or 1,8-bis( tert-butylphenylphosphino)naphthalene disulfide, rac- 5a. The compounds were characterized by NMR spectroscopy ( 1H, 31P, 13C). Crystal structures were determined by the X-ray method for (−)- 3a, rac- 4a, rac- 4a′ and rac- 5a; this allowed the determination of the absolute configuration ( S, S) for the more soluble adduct (−)- 3a. It was found that rac- 1a undergoes partial epimerization in boiling xylene to give the meso form.

A Digalla[1.1]ferrocenophane and Its Coordination Chemistry: Synthesis and Structure of [{Fe(η5-C5H4)2}2{GaMe}2] and of the Adducts [{Fe(η5-C5H4)2}2{GaMe(D)}2] (D = Monodentate Donor) and [{Fe(η5-C5H4)2}2{GaMe}2D] (D = Bidentate Donor)

Gentle warming of 1,1‘-bis(dimethylgallyl)ferrocene (1) leads to the formation of trimethylgallium and the thermolabile compound [{Fe(η5-C5H4)2}2{GaMe}2] (2), a [1.1]ferrocenophane featuring group 13 elements in bridging positions. While NMR data for 2 prove a dynamic structure in solution, X-ray data reveal an anti conformation of the ferrocenophane framework in the solid state. The anti conformation is maintained in the thermolabile adducts 2a−g, which are obtained from 2 and the donors diethyl ether (2a), pyridine (2b), pyrimidine (2c), quinoxaline (2d), DMSO (2e), pyrazine (2f), and dioxane (2g), by donor-exchange reactions (2b−g) or on gentle warming of the respective donor adducts of 1. Rodlike polymers are formed either by interaction of 2 with bidentate donors (2f,g) or by π-stacking effects of aromatic molecules acting as monodentate donors (2b−d). Steric requirements inhibit the complex formation between 2 and the donor phenazine. A cyclic voltammogram of 2b in pyridine reveals two reversible ox...

α‐Oxolactam Enamines as New Synthons in the Nenitzescu Reaction.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Val‐Ala Dipeptide Isosteres by Hydrocyanation of α′‐Amino α,β‐Unsaturated Ketones − Control of Stereoselectivity by the N‐Protecting Group

AbstractThree diastereoisomeric hydroxyethylene isosters of the Val‐Ala dipeptide were synthesized from α,β‐unsaturated ketones 1 derived from N‐Boc‐ and N,N‐dibenzyl‐L‐valine. The enones were hydrocyanated with diethylaluminum cyanide to give the corresponding β‐cyano ketones with the stereoselectivity depending on the protecting group. N‐Boc protected enone 1a gave a 1:1 mixture of anti and syn adducts 4a, 5a while the corresponding N,N‐dibenzyl compound 1c gave a 6:1 mixture of anti, syn adducts 4c, 5c. Borohydride reduction of the resulting cyano ketones is also controlled by the protecting group, resulting in opposite stereoselectivities for N‐Boc and N,N‐dibenzyl compounds. The cyano alcohols thus obtained were converted, in several steps, into two series of enantiomerically pure hydroxyethylene isosters of the Val‐Ala dipeptide. In the first series the hydroxy group and the N‐terminal of the isoster are internally protected through the formation of an oxazolidine; in the second series the hydroxy group and the C‐terminal are protected as lactone. Two oxazolidines (28, 29), corresponding to syn,syn and syn,anti 4‐hydroxy‐5‐amino acid isosters, and three lactones (23−25), corresponding to syn,syn, syn,anti, and anti,anti isosters were obtained by this approach. (© Wiley‐VCH Verlag GmbH & Co KGaA, 69451 Weinheim, Germany, 2003)

Synthesis of 2-Benzylphenols: Transformation of the Baylis-Hillman Adducts Derived from 2-Cyclohexen-1-one

an extension of the reaction, we intended to prepare acridine skeleton from the Baylis-Hillman adducts of 2-cyclohexen1-one as shown in Scheme 1. However, we could not prepare the desired compounds via the reaction scheme (vide infra). Instead, we could obtain 2-benzylphenol derivatives in good yields as shown in Scheme 2 and wish to report herein the results. The Friedel-Crafts alkylation reaction is one of the most powerful methods to form the carbon-carbon bond in organic reactions. The Friedel-Crafts benzylation reaction is of great synthetic significance in industrial processes. 3 However, synthesis of 2-benzylphenols regioselectively from phenols or benzyl phenyl ethers is difficult due to the formation of ortho-/para- mixtures. 4 Synthesis of these compounds by Fries rearrangement of phenyl phenylacylates also suffers from the formation of mixtures. 5 Ortho-specific alkylation of phenols via 1,3,2-benzodioxaborins was known. 6 1,3,2-Benzodioxaborins can be reduced to orthoalkyl phenols with tert-butylamine borane in the presence of aluminum chloride. The Baylis-Hillman reaction of 2-fluorobenzaldehyde (1a) and 2-cyclohexen-1-one (2) was carried out in aqueous THF with the aid of DMAP at room temperature to give the corresponding adduct 3a in 58% yield as reported previously. 7 Acetylation of 3a with Ac2O/DMAP gave 4a in 91% yield. Initially, we examined the reaction of 4a and ptoluenesulfonamide in the presence of K 2CO3 in DMF. However, 2-(2-fluorophenyl)methylphenol (5a) was isolated in 74% yield, unexpectedly. The formation of 5a occurred well without tosylamide. Actually, the yield of 5a was improved up to 94% without tosylamide as shown in Table 1 (entry 1). Thus, we prepared some Baylis-Hillman acetates of 2cyclohexen-1-one and examined their conversion to 2arylmethylphenols and the results are summarized in Table 1. As mentioned previously, the Baylis-Hillman reaction of 1 and 2 was carried out in aqueous THF in the presence of 0.1 equiv. of DMAP. 7 The corresponding adducts 3a-h were obtained in reasonable yields (41-64%) at room temperature. Following conversion to their acetate 4a-h was excellent in all cases (CH2Cl2, Ac2O/DMAP, rt, 90-98%). The reaction of 4a-f in DMF in the presence of K 2CO3 (1.0 equiv) gave 5a-f in good yields (89-96%) in short time (1-2 h) at 60-70 o C. 8 The formation of 5g, the quinoline derivative, was carried out at room temperature. The reaction is believed to occur as depicted in Scheme 2: potassium carbonate assisted elimination of acetic acid and the following keto-enol tautomerization and 1,5-hydrogen transfer. 9 We could not obtain the corresponding phenol derivative from the analogous reaction with 4h, derived from hexanal. Intractable mixtures were observed on tlc at 60-70 o C. Instead, we could isolate cyclohexenone derivative 6 in 40% yield at room temperature. 10 The structure of 6 was determined by 1 H, 13 C, and 1 H- 1 H COSY. 8 In conclusion we disclosed unusual transformation of the Baylis-Hillman acetates of 2-cyclohexen-1-one into 2arylmethylphenols. Further chemical transformation of the products to xanthene derivatives via the nucleophilic aromatic substitution strategy and the synthesis of acridines are underway.

Intramolecular [2 + 2] photocycloaddition of alkenes incorporated in a carbohydrate template. Synthesis of enantiopure bicyclo[3.2.0]heptanes and -[6.3.0]undecanes.

Intramolecular [2 + 2] photocycloaddition of alkenes with a furano sugar placed between them have been investigated under both copper(I)-catalyzed and sensitized conditions. The copper(I)-catalyzed photocycloaddition of the dienes 4a, 4b, and 4c led to unexpected formation of the thermodynamically less stable cis-syn-cis 4-5-5 tricyclic adducts 5a, 5b, and 5c, respectively. The sensitized photocycloaddition of the diene 14 also gave the cis-syn-cis adduct 15 showing that the copper(I) catalyst does not have any influence on the stereochemical course through coordination with the anomeric ring oxygen of the furano sugar. The identical stereochemical course observed under both catalyzed and sensitized photoaddition reactions have been attributed to be of steric origin. Bis(dienes) 25a and 25b, which gave an intractable mixture on copper(I)-catalyzed irradiation, underwent smooth photocycloaddition in the presence of benzophenone, and the resulting 1,2-divinyl cyclobutanes underwent spontaneous [3.3]-rearrangement at room temperature to produce bicyclo[6.3.0]undecanes 30a and 30b, respectively. This investigation provides an approach for the construction of enantiopure bicyclo[3.2.0]heptanes and -[6.3.0]undecanes.

Intramolecular Diels—Alder Reactions of Brominated Masked o‐Benzoquinones. A Detour Method to Synthesize Highly Functionalized Oxatricyclic [m.3.1.0] Ring Systems from 2‐Methoxyphenols.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Tris(pentafluorophenyl)borane adducts of substituted imidazoles: conformational features and chemical behavior upon deprotonation

Tris(pentafluorophenyl)borane adds to the donor nitrogen atom of 1,4,5-trimethyl- and 1-methyl-4,5-diphenylimidazole (5a,b) to yield the corresponding adducts 6a and 6b, respectively. Treatment of 1-methylbenzimidazole with B(C6F5)3 or B(C6H5)3 gave the related adducts 6c and 7, respectively. All four adducts were characterized by X-ray diffraction. In solution, the compounds 6 exhibit dynamic 19F NMR spectra, each featuring 15 separate 19F NMR resonances at low temperature. With increasing temperature a coalescence of the o-, m- and p-F signals of only a pair of –C6F5 signals is observed, leaving the set of five resonances of the third –C6F5 group unchanged. It required a further increase of the monitoring temperature to eventually observe the coalescence of the respective signals of all three –C6F5 groups. A DFT study revealed no specific intramolecular interactions of the F–C(Ar) substituents with other moieties of the molecules 6; a topological control is thus likely to have caused this remarkably specific dynamic behavior. Deprotonation of the compounds 6a and 6c at carbon atom C2 was achieved by treatment with methyllithium. The expected “Arduengo carbene anions” (8) are, however, not stable under the reaction conditions but rapidly react by an intramolecular nucleophilic aromatic substitution at one of the adjacent –C6F5 groups to yield the heterotricyclic products 9. The respective benzimidazole-derived compound 9c was also characterized by an X-ray crystal structure analysis.

η1 versus η5 Bonding Modes in Cp*Al(I) Adducts of 9-Borafluorenes

The reactivity of highly Lewis acidic perfluorinated borafluorenes C12F8BR (R = C6F5, 1a; CH3, 1b) and the nonfluorinated 9-phenyl-9-borafluorene (2) toward [Cp*Al]4 was investigated. The reaction of 1 with [Cp*Al]4 leads to the formation of thermally robust η1 Lewis acid−base adducts 3a,b as the thermodynamically favored products. Use of the less Lewis acidic 2 does not alter the mode of reactivity, with the η1 Lewis acid−base 4 formed preferentially. Reduction of 2 to the 9-boratafluorene 2·Li2(THF)n is readily accomplished in THF solution. However, reaction of 2·Li2(THF)n with [Cp*AlCl2]2 or Cp*AlCl2(THF), 5, affords aluminum metal, 2·THF, and Cp*H as the main identifiable products. Compounds 3a, 3b, 4, and 5 were fully characterized including their X-ray structures. A DFT computational study was conducted to probe the reason for the strong preference for η1 bonding, which essentially stems from the localization of aromaticity in the flanking phenyl rings in the 9-borafluorene ring system.

An improved procedure for the asymmetric aldol reaction of the titanium enolate of an N3-propionyl-3,4,5,6-tetrahydro-2 H-1,3,4-oxadiazin-2-one

The direct formation of the titanium enolate of N 3-propionyl-3,4,5,6-tetrahydro-2 H-1,3,4-oxadiazin-2-one has been achieved through complexation with titanium tetrachloride at 25°C, followed by deprotonation with triethylamine (−78 to 25°C). The preformed titanium enolate has been reacted with D 2O/DCl to afford deuterated derivative 6 and also reacted with a series of aromatic and aliphatic aldehydes affording aldol adducts 4a– f with crude diastereoselectivities ranging from 8:1 to 38:1.

Quantum chemical study on enantioselective reduction of keto oxime ether with borane catalyzed by oxazaborolidine. Part 3. Properties of intermediates during hydride transfer

AbstractIn the current article, the structures and properties of intermediates during the hydride transfer for the prior coordination of the carbonyl oxygen of keto oxime ether at B(2) of oxazaborolidine are discussed. All the structures are optimized completely by means of the Hartree–Fock (HF) and the density functional methods at the HF/6‐31G(d) and Becke's three‐parameter exchange functional and the gradient‐corrected functional of Lee, Yang, and Paar (B3LYP)/6‐31G(d) levels. The hydride transfer from BH3 to the carbonyl carbon in oxazaborolidine‐borane‐keto oxime ether adduct results in the formation of the adduct 4a* with a seven‐membered ring. This adduct has four stable structures. Another hydride of BH2 transfers to the oxime carbon in 4a*, leading to the adduct 5a*, which has also four stable structures. Among all the structures of 5a*, the most stable structure can generate (1S, 2R)‐cis amino alcohol, which is in agreement with that obtained in the experiment. This enantioselective reduction may go through the process in which oxazaborolidine‐borane‐keto oxime ether adduct is directly transformed into the adduct 4a* with a seven‐membered ring. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 93: 307–316, 2003

Platinum complex catalyzed reaction of tributyltin cyanide with alkynes

In the presence of a catalytic amount (5 mol%) of a platinum complex, tributyltin cyanide ( 1) reacts with dimethyl- ( 2a) or diethyl acetylenedicarboxylate ( 2b) to afford cyanostannylation adducts ( 3a, b) in excellent yields. The reaction proceeds highly selectively affording only a ( Z)-isomer. The compounds 3a, b are novel products which possess synthetically useful cyano, alkenylstannyl and alkoxycarbonyl functionalities in the same molecule. Two alkoxycarbonyl functionalities may be indispensable on each alkyne carbon to accomplish the cyanostannylation reaction. Reaction with terminal alkynes gave the stannylated product ( 6).

Toward the development of a structurally novel class of chiral auxiliaries: diastereoselective aldol reactions of a (1R,2S)-ephedrine-based 3,4,5,6-tetrahydro-2H-1,3,4-oxadiazin-2-one.

[reaction: see text] Asymmetric aldol addition reactions have been conducted with (1R,2S)-ephedrine-derived 3,4,5,6-tetrahydro-2H-1,3,4-oxadiazin-2-one (2). Diastereoselectivities range from 75:25 to 99:1 for the formation of the crude non-Evans syn adducts 8a-h. The facial selectivity of the enolate is directed by the stereogenic N(4)-methyl substituent. Aldol adduct 8a is readily cleaved by acid hydrolysis to afford (2S,3S)-3-hydroxy-2-methyl-3-phenylpropionic acid (9) in >95% ee.

4 + 2]-Cycloaddition Reactions Involving α-Oxo Thioketone Intermediates

α-Chloro β-oxo sulfenyl chlorides 2 were reduced by iodide ions to the corresponding α-oxo thioketones 3 which dimerized in situ in a hetero-[4 + 2] cycloaddition to give the 1,3,4- oxadithiin derivatives 4. The α-oxo thioketones 3, in situ, cyclized also with 2,3-dimethyl-1,3- butadiene to give the corresponding adducts 5 and only in case of the oxo thioketone intermediate 3d two products 4d and 5d were obtained. Also, The α-oxo thioketones 3a,c, underwent in situ, cycloaddition with furan to give the corresponding adducts 6a,c together with the corresponding thioketone dimers 4a,c. When this reaction was carried out in the presence of diethyl acetylenedicarboxylate or chalcone derivative 8, only the oxo thioketone dimers 4a-d were obtained.

Stereochemistry of the [4 + 2] cycloadditions of trans,trans- and cis,trans-2,4-hexadiene to C(60).

The [4 + 2] cycloaddition of trans,trans-2,4-hexadiene with C(60) proceeds via a concerted mechanism with retention of stereochemistry in the cycloadduct 1a. However, when cis,trans-2,4-hexadiene reacts with C(60), isomerization of the cis,trans to the thermodynamically more stable trans,trans isomer occurs. Subsequently, the cis,trans diene isomerized to the trans,trans isomer and cycloadds to C(60), to form adduct 1a. When the reaction is carried out at higher temperatures, the formation of cycloadduct 1b is also obtained. This result is consistent with a concerted cycloaddition of cis,trans-2,4-hexadiene with C(60), which is more reactive at elevated temperatures and leads to the formation of the Diels-Alder adduct 1b.

Cationic complexes of iridium: diiodobenzene chelation, electrophilic behavior with olefins, and fluxionality of an Ir(I) ethylene complex.

The synthesis of a series of dicationic Ir(III) complexes is described. Reaction of Ir(CO)(dppe)I (dppe = 1,2-bis(diphenylphosphino)ethane)) with RI (R = CH(3) and CF(3)) results in formation of the Ir(III) precursors IrR(CO)(dppe)(I)(2) (R = CH(3) (1a) and CF(3) (1b)). Subsequent treatment with AgOTf (OTf = triflate) generates the bis(triflate) analogues IrR(CO)(dppe)(OTf)(2) (R = CH(3) (2a) and CF(3) (2b)), which undergo clean metathesis with NaBARF (BARF = B(3,5-(CF(3))(2)C(6)H(3))(4)(-)) in the presence of 1,2-diiodobenzene (DIB) forming the dicationic halocarbon adducts [IrR(CO)(dppe)(DIB)][BARF](2) (R = CH(3) (3a) and CF(3) (3b)). Complexes 3a and 3b demonstrate facile exchange chemistry with acetonitrile and carbon monoxide forming complexes 4 and 5, respectively. NMR investigation of the mechanism reveals that the process proceeds through an eta(1)-diiodobenzene adduct, where labilization at the coordination site trans to the alkyl group occurs first. Complex 3a reacts with ethylene forming the cationic iridium(I) product [Ir(C(2)H(4))(2)(CO)(dppe)][BARF] (6), which demonstrates fluxional behavior. Variable-temperature NMR studies indicate that the five-coordinate complex 6 undergoes three dynamic processes corresponding to ethylene rotation, Berry pseudorotation, and intermolecular ethylene exchange in order of increasing temperature based on NMR line shape analyses used to determine the thermodynamic parameters for the processes. The DIB adducts 3a and 3b were also found to promote olefin isomerization of 1-pentene, and polymerization/oligomerization of styrene, alpha-methylstyrene, norbornene, beta-pinene, and isobutylene via cationic initiation.

The Behaviour of 1,2,3-Indantrione Towards Wittig-Horner Reagents

Wittig-Horner reagents 1a,b react with 1,2,3-indantrione (2) to give the dimeric adducts 3a and 3b, respectively. Moreover, 2 reacts with tert-butyl diethyl-phosphonoacetate (1c) yielding the ethylenic compound 4. On the other hand, 2 reacts with 1d to yield the phosphonate adduct 5. Mechanisms accounting for the formation of the new products are discussed and the probable structures of the products are presented based on compatible analytical and spectral data.