Nucleophilic difluoromethylation and difluoromethylenation of aldehydes and ketones using diethyl difluoromethylphosphonate

New methodology for difluoromethylation and difluoromethylenation of aldehydes and ketones based on nucleophilic fluorination using diethyl difluoromethylphosphonate (1) was developed.     

Alkoxide-induced nucleophilic trifluoromethylation using diethyl trifluoromethylphosphonate

A novel alkoxide-induced nucleophilic trifluoromethylation of carbonyl compounds, disulfides, and diselenides using diethyl trifluoromethylphosphonate is presented. In these reactions diethyl trifluoromethylphosphonate acts as a synthon.     

Nucleophilic (phenylsulfinyl)difluoromethylation of carbonyl compounds with difluoromethyl phenyl sulfoxide

We have successfully achieved nucleophilic (phenylsulfinyl)difluoromethylation of both enolizable and non-enolizable aldehydes and ketones by using difluoromethyl phenyl sulfone (1) as the fluoroalkylating agent. Although the chemical yields of the reactions are good to excellent, the observed diastereoselectivity is poor (dr = 1:1.04-2.03). The present synthetic methodology provides a convenient alternative for the preparation of α-(phenylsulfinyl)difluoromethylated carbinols that were previously synthesized via a two-step procedure.     

Nucleophilic transformations of cyclic phosphate triesters

Reactions of cyclic phosphate triesters, such as 2-ethoxy-1,3,2-dioxaphospholane 2-oxide, with Grignard reagents such as phenyl-, alkyl-, ethynyl-, and allyl-magnesium halides result in ring opening leading to the corresponding phosphonates, via nucleophilic attack of carbon on the phosphorus atom. Treatment of 2-ethoxy-1,3,2-dioxaphospholane 2-oxide with sodium borohydride yields ethyl 2-hydroxyethyl phosphite. This reaction is exclusive for the five-membered cyclic system: under these conditions acyclic phosphate triesters, such as triethyl phosphate, are unreactive and the analogous six-membered ring system, 2-ethoxy-1,3,2-dioxaphosphorinane 2-oxide reacts only partially to give unidentified phosphate esters and traces of phosphonate products. Both compounds were inert to NaBH₄.     

Nucleophilic Addition Reactions of Tricarbonyl [η5-1-(Phenylthio)Cyclohexadienyl]Iron(I) Complex

Hydride abstraction of tricarbonyl[η⁴phenylthio)-l,3-cyclohexadiene]iron(0) complex 2 with Ph₃C⁺PF₆^? regiospecifically provided the title compound 3 in excellent yield. Cationic complex 3 could react with a variety of nucleophiles in good yield. Hard nucleophiles prefer to attack at the C-l position, whereas soft and hindered nucleophiles favor attack at the C-5 position. Some synthetic applications were also studied.     

Synthesis of (purin-6-yl)methylphosphonate bases and nucleosides

Three approaches to the synthesis of the title (purin-6-yl)methylphosphonates were investigated and compared. While, the Arbuzov reaction of 6-(iodomethyl)purines with triethyl phosphite did not work, Michaelis-Becker alkylation of the sodium salt of diethyl phosphonate with 6-(mesyloxymethyl)purines gave the desired products in good yields. The best method was based on Rh- or Pd-catalyzed cross-coupling reactions of 6-iodopurines with (diisopropoxyphosphorylmethyl)zinc bromide. In this way a small series of 6-(diisopropoxyphosphorylmethyl)purine bases and nucleosides was prepared in high yields.     

Synthesis of α-allenic aldehydes and allenyl trimethylsilyl ketones via (trimethylsilyloxy)butatrienes

α-Lithiated (trimethylsilyloxy)butatrienes, generated by 1,4-elimination of methanol from 1-trimethylsilyloxy-4-methoxy-2-alkynes with tert-butyllithium, give mixtures of α-allenic aldehydes and allenyl trimethylsilyl ketones which can be separated by distillation. The ratio aldehyde/ketone is solvent dependent.     

Nucleophilic Addition Reactions of Tricarbonyl [η5−1-(Phenylsulfonyl)cyclohexadienyl]iron(I) Complex

Hydride abstraction of tricarbonyl[η⁴-1-(phenylsulfonyl)-1,3-cyclohexadiene]iron(0) complex 2 with Ph₃C⁺PF₆^? regiospecifically provided the title compound 3 in excellent yield. Cationic complex 3 could react with a variety of nucleophiles in good yields. Soft nucleophiles prefer to attack at the C-5 position, whereas hard nucleophiles such as methyllithium and the enolate of ethyl acetate gave the C-5 as well as the C-2 addition products. Some synthetic applications of the addition products were also studied.     

New methodology for the deoxygenative difluoromethylenation of aldehydes and ketones; unexpected formation of tetrafluorocyclopropanes

Generation of difluoromethylene phosphorus ylides in the presence of aldehydes and ketones results in Wittig-type reactions to give gem-difluoroalkenes. Subsequent in situ addition of difluorocarbene (carbenoid) can occur (increased with triphenylphosphine and decreased with tributylphosphine) to give tetrafluorocyclopropanes. [Reaction: see text]     

Bis(trimethylsilyl)chromate catalyzed oxidations of alcohols to aldehydes and ketones with periodic acid

A facile, selective and high yielding bis(trimethylsilyl) chromate (BTSC) catalyzed selective oxidation of alcohols to aldehydes and ketones with periodic acid is reported.     

Chlorodimethylaluminum-promoted nucleophilic addition of lithium pentamethylcyclopentadienide to aliphatic aldehydes and DDQ-mediated carbon-carbon bond cleavage of the adducts providing the parent aldehydes

Treatment of aliphatic aldehyde with lithium pentamethylcyclopentadienide in the presence of chlorodimethylaluminum provided the corresponding carbinol in excellent yield. The carbinol returns to the parent aldehyde and pentamethylcyclopentadiene by the action of a catalytic amount of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ).     

Regio- and Stereocontrolled Nucleophilic Addition Reactions of An Unsymmetrically Disbustituted Butadiene η4-Molybdenum Cationic Complex

The reactions of a new cationic complex, [Cp(CO)₂Mo(η⁴-2-methyl-3-SPh-C₄H₄)]⁺ PF^?₆ (3), with carbon, hydride, and nitrogen nucleophiles were found to give only the C-1 addition products in good yield. The X-ray crystal structures of two of the addition products 4a and 4e confirm the regio- and stereochemistry of the nucleophilic additions.     

The preparation of phenyl ketones using (phenylthio)pehnyl-(trimethylsilyl)methyl-lithium

Phenyl ketones are prepared by alkylation of (phenylthio)phenyl(trimethylsilyl)methyl-lithium followed by oxidation and rearrangement.     

2-芳酰氨基-5-苄基-1,3,4-噻二唑上亚甲基与4-二甲氨基苯甲醛加成反应

1,3,4—噻二唑杂环化合物具有广泛的生物活性,如调节植物生长,杀菌,除草,杀虫等。因此它的合成及其反应引起了化学家的兴趣。Elmoghayar等报道了2—芳酰氨基—5—氰甲基—1,3,4—噻二唑中活泼亚甲基与苯甲醛的反应生成2—芳酰氨基—5—(1＇—氰基苯乙烯基)—1,3,4     

One-pot synthesis of 1,4-dihydro-3,1-benzoxazine-2-thiones by the reaction of 2-lithiophenyl isothiocyanates with aldehydes or ketones

An efficient one-pot method for the synthesis of 4-monosubstituted and 4,4-disubstituted 1,4-dihydro-3,1-benzoxazine-2-thiones has been developed. Treatment of 2-bromophenyl isothiocyantes with butyllithium in THF at −78 °C generates 2-lithiophenyl isothiocyanates, which are allowed to react with various carbonyl compounds, including aldehydes, ketones, and butanolide, to give the corresponding desired products in moderate to good yields.     

Chemistry of selected cyclic P(III) compounds possessing a P-Cl bond

The compounds [CH₂(6-t-Bu-4-Me-C₆H₂O)₂]PCl (1), (OCH₂CMe₂CH₂O)-PCl (2), and [ClPN(t-Bu)]₂ (3) have been utilized as precursors in the synthesis of (i) new pentacoordinate phosphorus compounds [e.g. CH₂(6-t-Bu-4-Me-C₆H₂O)₂ P(NRR′)(O₂C₆C1₄), CH₂(6-t-Bu-4-Me-C₆H₂O)₂PX[OC(O-i-Pr)N=N(C(O)O-i-Pr)],(ii) cyclic phosphates and their complexes [e.g. imidazolium⁺CH₂(6-t-Bu-4-Me-C₆H₂O)₂PO₂ ^-.MeOH], (iii) new cycloaddition products [e.g. CH₂(6-t-Bu-4-Me-C₆H₂O)₂PC(CO₂Me)C(CO₂Me)C(O)N, (iv) macrocyclic compounds [e.g. [(t-BuN)P]₂[-OCH₂CMe₂CH₂O-]_h2] and (v) phosphonates [e.g. (OCH₂CMe₂CH₂O)P (O)CH₂C(CN)=CHC₅H₄FeC₅H₅]. The synthetic and structural aspects of these new products are discussed.     

Sodium trifluoroacetate: an efficient precursor for the trifluoromethylation of aldehydes

In a convenient and efficient procedure, the nucleophilic trifluoromethylation of aldehydes with sodium trifluoroacetate was achieved, using copper(I) halides as the catalyst.     

Pentamethylcyclopentadienide in organic synthesis: nucleophilic addition of lithium pentamethylcyclopentadienide to aromatic aldehydes and carbon-carbon bond cleavage of the adducts affording the parent aldehydes

Treatment of aromatic aldehyde with lithium pentamethylcyclopentadienide provided the corresponding carbinol in excellent yield. The carbinol returns to the parent aldehyde and pentamethylcyclopentadiene upon exposure to an acid or due to heating. The combination of the two reactions can represent a protection of aromatic aldehyde.     

Addition of halogenoacetic esters to aldehydes and ketones in the presence of Fe(CO)5

The use of complex-forming solvents and variations in the reaction temperature made it possible to prepare α-halogeno β-hydroxy carboxylic esters upon addition of halogenoacetic esters to aldehydes and ketones promoted by iron pentacarbonyl. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 718–720, April, 2000.     

Nucleophilic, radical, and electrophilic (phenylsulfonyl)difluoromethylations

Selective incorporation of a fluoroalkyl moiety to modulate the properties of an organic molecule has become a frequently used strategy in life science- and materials science-related applications. In this context, selective introduction of a (phenylsulfonyl)difluoromethyl group (PhSO₂CF₂) into organic molecules has attracted much attention, since the PhSO₂CF₂ group can be regarded as a “chemical chameleon” that can be readily transformed into difluoromethyl (CF₂H), difluoromethylene (–CF₂–), and difluoromethylidene (CF₂) functionalities. This article overviews the recent development of (phenylsulfonyl)difluoromethylation reactions from 2003, including the nucleophilic (phenylsulfonyl)difluoromethylations with PhSO₂CF₂H, PhSO₂CF₂SiMe₃ and PhSO₂CF₂Br reagents, free radical (phenylsulfonyl)difluoromethylations with PhSO₂CF₂I reagent, and electrophilic (phenylsulfonyl)difluoromethylations with a hypervalent iodine(III)-CF₂SO₂Ph reagent.