Products in the Reactions of Trialkyl Phosphites with α-Halogeno-acetophenones in Alcoholic Media

Abstract

α-Hydroxyphosphonates are formed, in addition to vinyl phosphates and dehalogenated ketones, in the reactions of trimethyl phosphite (in methanol) or triethyl phosphite (in ethanol) with variously substituted α-chloro, α-bromo, and α,α,-dichloro-acetophenones. Tri-isopropyl phosphite in propan-2-ol gives only the vinyl phosphate. Ketophosphonates are not detectable amongst the reaction products under the conditions used. Trends in product composition can be correlated with the leaving ability of halogen, substituent effects, structure of the phosphite, and reaction temperature. Reactant ratios may also influence the product composition. The reactions of trimethyl phosphite in methanol with 4-nitro-α-chloroacetophenone, or α,α-dichloroacetophenones yield the dehalogenated α-hydrogxyphosphonates in addition. In the case of the 4-nitro derivative, this product cannot be accounted for by reaction of the phosphite with dehalogenated ketone (4-nitroacetophenone). Dehalogenation of the first-formed α-hydroxyphosphonate was, however, shown to occur under reaction conditions and appears to require the removal of positive chlorine, followed by protonation. Reactions of the α,α-dichloroacetophenones were similar to those of the α-chloroacetophenones, giving the corresponding chlorovinyl phosphate, α,α-dichloro-α-hydroxyphosphonate, and monodehalogenated ketone(i.e. α-chloroacetophenone); the latter was not however detected as it reacted further with excess phosphite to give the expected products as described above. Possible mechanisms for the various reactions are discussed. The ¹H and ¹³C nmr spectra of the α-hydroxy-phosphonates show magnetic non-equivalence of the two alkoxy groups, attributed to restricted rotation about the P-C bond as a result of intramolecular hydrogen-bonding.     

Photocycloadditions of tetrachloro-1,4-benzoquinone (chloranil) onto cyclobutene and cyclopropene. Expected and unexpected products

Solutions of chloranil (CA) in chlorobenzene were irradiated in the presence of cyclobutene and cyclopropene. Cyclobutene gave rise to two conventional 1 : 2 cycloadducts onto the dichloroethene subunits of CA and an α,β-unsaturated α,γ-dichloro-γ-lactone. Heating of the crude product in methanol converted the lactone into an α,β-unsaturated methyl γ-oxocarboxylate (25% yield) and a large amount of the major 1 : 2 cycloadduct, which contains chlorocyclobutane entities, into a cyclopropylcarbinyl chloride derivative (24% yield). An entirely new product type was the result in the case of cyclopropene. After treatment of the crude product with methanol a tetracyclic acetal containing a cyclopentanone and a dihydropyran subunit was isolated in 36% yield. Apparently, CA had taken up two molecules of cyclopropene. One of the resulting cyclopropane entities must have undergone a rearrangement en route to the final product.     

Ni-catalyzed α-arylation of secondary α-bromo-α-fluoro-β-lactam: cross-coupling of a secondary fluorine-containing electrophile

A highly diastereoselective cross-coupling reaction of an α-bromo-α-fluoro-β-lactam with a wide range of aryl Grignard reagents was catalyzed by Ni/bis(oxazoline) in yields of up to 98%. The product was obtained diastereoselectively as an anti-isomer. This is the first successful α-arylation of an α-fluoro-β-lactam to produce diverse α-aryl-α-fluoro-β-lactams.     

Polymerization and copolymerization of α-methacrylophenone

Under a variety of conditions it has not been possible to induce the free-radical-initiated homopolymerization of α-methacrylophenone (α-MAP). The only product isolated from such efforts was the Diels-Alder dimer of the monomer. A Mayo-Lewis plot of the free-radical copolymerization of α-MAP and styrene shows considerable scatter but the copolymer composition indicates that an α-MAP unit can add to itself. These results have been ascribed to a penultimate effect. α-MAP is homopolymerized by dimsylsodium or n-butyllithium. Attempted copolymerization of α-map and styrene with n-butyllithium produces >95% α-MAP. Unexpectedly, α-MAP does not homopolymerize with lithium dispersion, but does react in the presence of styrene to give product containing a relatively small amount of α-MAP.     

An α-diaminoboryl carbanion assisted stereoselective single-pot preparation of α,β-disubstituted acrylonitriles

An α-diaminoboryl carbanion-mediated one-pot olefination directly converts an acetonitrile or the homologous nitrile into a series of α,β-disubstituted acrylonitriles in a stereoselective manner. The protocol involves the formation of an α-substituted α-diaminoboryl acetonitrile and subsequent olefination with an aldehyde. The use of an aryl or conjugated aldehyde preferentially leads to a (Z)-acrylonitrile, while an aliphatic aldehyde gave an (E)-isomer as a major product. Two complementary approaches, a linear method and a divergent method, are developed.     

The photolysis of some α-iodo-nitroalkanes in solution

α-Iodo-nitroalkanes decompose photochemically into α-nitroalkyl radicals and iodine. The α-nitroalkyl radical is detected by trapping with 2-methyl-2-nitrosopropane and identified by the hfs-constants of the resulting β-nitronitroxide observed with ESR. In the absence of nitroso compounds the α-nitroalkyl radicals can lose hydrogen to give nitro-olefins (70–80%). Minor products are nitroalkane (<5%) and ketone (10%), the latter via rearrangement of the α-nitroalkyl radical and loss of NO. When the HI elimination is blocked, as is the case with 2-iodo-2-nitroadamantane, the yield of ketone increases to 80%. Upon stabilization of the α-nitroalkyl radical by a phenyl group, dimerization becomes important. In the case of 1-cyclopropyl-1-iodo-1-nitroethane a considerable amount of ring opened product is isolated.     

大位阻、富电子MOP型烷基膦配体在钯催化的1,3-二羰基化合物 α-芳基化反应中的应用

富电子、大位阻MOP型烷基膦配体2-二叔丁基膦-2’-异丙氧基-1,1’-联萘(L1)在钯催化的1,3-二羰基化合物的α-芳基化反应中显示了较好的催化活性. 在这类催化反应中, 碱的选择具有重要的影响: 以K3PO4为碱, Pd(OAc)2/L1催化体系在丙二酸二乙酯的α-芳基化中, 富电子溴代芳烃显示较好的活性; Pd(OAc)2/L1催化的乙酰乙酸乙酯α-芳基化时, 以 K2CO3为碱, 催化体系显示较好的活性, 这个催化体系可控制反应得到α-芳基乙酰乙酸乙酯, 而不是脱乙酰基的产物. 较为惰性的氯代芳烃在Pd(OAc)2/L1的催化下, 也能够跟1,3-二羰基化合物发生α-芳基化反应.     

Isochinoline. 1. Mitteilung. Über die Umlagerung von α, α-Dialkylhomophtalimiden zu Derivaten des 1-Chlor-3, 4-dialkyl-isochinolins

On reinvestigation of the reaction of wet phosphorus oxychloride with α,α-dimethylhomophthalimide, 1-chloro-3-chloromethyl-4-methyl-isoquinoline and 1-chloro-4-chloromethyl-3-methyl-isoquinoline were isolated as the main products (aside from some substances resulting from a redox disproportionation). The production of these two substances can be rationalized by assuming a mechanism in which the rearrangement product is a protonated derivative of 3,4-dimethylene-3, 4-dihydroisoquinoline. With α, α-diethyl-homophthalimide the only isolated product was a derivative of 1-chloro-3, 4-diethyl-isoquinoline, with a chlorine atom in β-position of one of the ethyl groups, while with α-methyl-α-benzyl-homophthalimide the isolated product was 1,3-dichloro-4-methyl-isoquinoline, i.e. elimination had taken place instead of rearrangement. Also these results are in agreement with the proposed mechanism.     

C-nitroso compounds—XXXI: The addition of α-chloronitroso compounds to olefins containing allylic hydrogen

α Chloronitrosoadamantane 1a gives upon reaction with 2-phenylpropene at room temperature virtually quantitatively a stable ketonitrone salt, the α,α-adamantylidene-N-(2-phenyl)prop-1-en-3-yl nitrone hydrochloride 2a. Evidence for the structure of the crystalline product is based on microanalytical data and spectroscopic properties, together with degradation studies. Similar aliphatic ketonitrone hydrochlorides have been obtained from reaction of 2-phenylpropene with other α-chloronitroso compounds 1b-1e (73–91%), and from α-chloroni-trosoadamantane . and a series of allylic olefins (76–95%). Rearrangement of an intermediary N-α-chloroalkyl-N-alkenylhydroxylamine, which has been initially formed by an ene-type process between the reactants, can explain formation of the product.     

Metal-Free Aminomethylation of Aromatic Sulfones Promoted by Eosin Y

A metal-free α-aminomethylation of heteroaryls promoted by eosin Y under green light irradiation is reported. A large variety of α-trimethylsilylamines as precursor of α-aminomethyl radical species were engaged to functionalize sulfonyl-heteroaryls following a Homolytic Aromatic Substitution (HAS) pathway. This method has provided a range of α-aminoheteroaryl compounds including a functionalized natural product. The mechanism of this late-stage functionalization of aryls was investigated and suggests the formation of a sulfonyl radical intermediate over a reductive quenching cycle.     

Reaction of α,β-unsaturated acid chlorides with β-diketones. Synthesis of 4,6,7,8-tetrahydro-2H-1-benzopyran-2,5(3H)-diones

Reaction of an α,β-unsaturated acid chloride with the anion of 5,5-dimethyl-1,3-cyclohexane-dione ( 2 ) gives either the enol ester ( 4 ) or a cyclized product ( 5 ), depending upon the reaction conditions. When the acid chloride is in excess, the ester is obtained. When the anion is in excess and the acid chloride is acryloyl or crotonyl, the cyclized product is obtained. A similar cyclized product ( 9 ) was formed from acryloyl chloride and an excess of the anion of 4-hydroxy-6-methyl-2-pyrone ( 8 ).     

Using nonproduct quadrature grids to solve the vibrational Schrödinger equation in 12D

In this paper we propose a new quadrature scheme for computing vibrational spectra and apply it, using a Lanczos algorithm, to CH(3)CN. All 12 coordinates are treated explicitly. We need only 157'419'523 quadrature points. It would not be possible to use a product Gauss grid because 33 853 318 889 472 product Gauss points would be required. The nonproduct quadrature we use is based on ideas of Smolyak, but they are extended so that they can be applied when one retains basis functions θ(n(1))(r(1))···θ(n(D))(r(D)) that satisfy the condition α(1)n(1) + ··· + α(D)n(D) ≤ b, where the α(k) are integers. We demonstrate that it is possible to exploit the structure of the grid to efficiently evaluate the matrix-vector products required to use the Lanczos algorithm.     

Asymmetric Michael addition of malonic diesters to acrylates by phase-transfer catalysis toward the construction of quaternary stereogenic α-carbons

A highly enantioselective construction of an all-carbon quaternary stereogenic center at the α-position of malonic diesters has been achieved by Michael addition using phase-transfer catalysis. The reaction of α-monosubstituted malonates with acrylates in the presence of N-(9-anthracenylmethyl)quininium chloride as a phase-transfer catalyst afforded the corresponding α,α-disubstituted malonic diesters in high chemical yields (up to >95% yield) with high enantioselectivities (up to 95% ee). Furthermore, the product was amenable to chemoselective transformation and could be successfully converted to the corresponding α,α-disubstituted amino acid derivatives through Curtius rearrangement.     

Enzymatic diastereo- and enantioselective synthesis of α-alkyl-α,β-dihydroxyketones

An enzymatic strategy for the preparation of optically pure α-alkyl-α,β-dihydroxyketones is reported. Homo- and cross-coupling reactions of α-diketones catalyzed by acetylacetoin synthase (AAS) produce a set of α-alkyl-α-hydroxy-β-diketones (30-60%, ee 67-90%), which in turn are reduced regio-, diastereo-, and enantioselectively to the corresponding chiral α-alkyl-α,β-dihydroxyketones (60-70%, ee >95%) using acetylacetoin reductase (AAR) as catalyst. Both enzymes are obtained from Bacillus licheniformis and used in a crude form. The relative syn stereochemistry of the enantiopure α,β-dihydroxy products is assigned by NOE experiments, whereas their absolute configuration is determined by conversion of the selected 3,4-dihydroxy-3-methyl-pentan-2-one to the natural product (+)-citreodiol.     

FACTORS IN THE CONTROL OF PRODUCT COMPOSITION IN THE REACTIONS OF TRIALKYL PHOSPHITES WITH α-HALOGENOACETOPHENONES IN ALCOHOLIC MEDIA

Abstract

α-Hydroxyphosphonates are formed, in addition to vinyl phosphates and dehalogenated ketones, in the reactions of trimethyl phosphite (in methanol) or triethyl phosphite (in ethanol) with variously substituted α-chloro, α-bromo, and α,α-dichloro-acetophenones. Tri-isopropyl phosphite in propan-2-ol gives only the vinyl phosphate. Ketophosphonates are not detectable amongst the reaction products under the conditions used. Trends in product composition can be correlated with the leaving ability of halogen, substituent effects, structure of the phosphite, and reaction temperature. Additional products are obtained in the reactions of trimethyl phosphite in methanol with 4-nitro-α-chloroacetophenone, which gives the dehalogenated hydroxyphosphonate, and with the α,α-dichloroacetophenones which undergo monodehalogenation. Twenty three new α-hydroxyphosphonates are reported.     

基于罗丹明和BODIPY单元的FRET探针的合成及其对小分子α-酮戊二酸的检测

小分子α-酮戊二酸(α-KA)是人体新陈代谢的一种十分重要的产物,与多种疾病存在直接或者间接的关系,可以对临床诊断提供帮助。以BODIPY单元作为能量给体、罗丹明单元作为能量受体,利用二者存在重叠的光谱,本文设计了一种基于罗丹明和BODIPY单元的荧光共振能量转移(FRET)探针,通过将罗丹明与BODIPY的衍生物进行桥联,得到能够检测α-酮戊二酸的荧光比率型探针RDM-BO。研究表明,探针RDM-BO本身的荧光光谱与BODIPY单元类似,当探针与α-酮戊二酸发生反应时,RDM-BO中的罗丹明单元会发生开环反应,使分子的共轭发生变化,同时产生新的荧光峰,检测效果显著,检测限可达到3.14μmol·L-1。     

Gas-phase ion-molecule reaction of alpha-phenylvinyl cation towards substituted benzenes in the environment of an ITMS

Ion-molecule reactions between the α-phenylvinyl cation (α-PVC) and mono-substituted benzenes have been investigated using a quadrople ion-trap mass spectrometer. The α-PVC, generated by chemical ionization from phenylacetilene, was found to react selectively with mono-substituted benzenes bearing electron withdrawing groups to give the product ions [M + 103](+) and the trans-vinylating product ions [M + 25](+). To characterize the reaction products, a combination of collision-induced dissociation, isotope-labeling experiments and model compounds were used. The results indicate, in addition to direct heteroatom alkylation, high extent of ortho attack. We attributed the positional selectivity of the α-PVC to the nature of the substituent on the neutral molecule. In particular, hydroxy and amino groups promoted the alkenylation at ortho position.     

Rational solution growth of α-FeOOH nanowires driven by screw dislocations and their conversion to α-Fe2O3 nanowires

We report the rational synthesis of α-FeOOH (goethite) nanowires following a dislocation-driven mechanism by utilizing a continuous-flow reactor and chemical equilibria to maintain constant low supersaturations. The existence of axial screw dislocations and the associated Eshelby twist in the nanowire product were confirmed using bright-/dark-field transmission electron microscopy imaging and twist contour analysis. The α-FeOOH nanowires can be readily converted into semiconducting single-crystal but porous α-Fe(2)O(3) (hematite) nanowires via topotactic transformation. Our results indicate that, with proper experimental design, many more useful materials can be grown in one-dimensional morphologies in aqueous solutions via the dislocation-driven mechanism.     

Concise assembly of linear α(1→6)-linked octamannan fluorescent probe

Synthesis of a fluorescently labelled (dansylated) linear α(1→6)-linked octamannan, using glycosyl fluoride donors and thioglycosyl acceptors, is described. A selective and convergent two-stage activation progression was executed to construct di-, tetra, and octa-mannosyl thioglycosides in three glycosylation steps with excellent yield. Further, a 5-N,N-dimethylaminonaphthalene-1-sulfonamidoethyl (dansyl) group was coupled to 1-azidoethyl octamannosyl thioglycoside. Global deprotection of the coupled product afforded the desired dansylated homo-linear α(1→6)-linked octamannan.