Organic hydrogen phosphites and hydrogen phosphates catalyzed Friedel-Crafts amidoalkylation of indoles with aryl aldimines

A highly efficient and selective Friedel-Crafts amidoalkylation reaction of indoles with N-Ts aryl aldimines has been developed utilizing dimethyl hydrogen phosphite or diphenyl hydrogen phosphate as the organocatalysts, providing a facile and cost-effective process for synthesis of 3-indolyl methanamine derivatives in good to excellent yields. This transformation displays a broad substrate scope and wide functional-group tolerability, regardless of the electronic and steric properties of N-Ts aryl aldimines. Given that the developed catalytic Friedel-Crafts amidoalkylation reaction exhibits several salient features such as metal-free catalysis, high efficiency, low cost and mild reaction condition, this process might have practical applications in the synthesis of 3-indolyl methanamine derivatives.     

Double nucleophilic 1,2-addition of silylated dialkyl phosphites to 4-phosphono-1-aza-1,3-dienes: synthesis of gamma-phosphono-alpha-aminobisphosphonates

gamma-Phosphono-alpha-aminobisphosphonates were synthesized from a new class of 4-phosphono-1-aza-1,3-dienes by the addition of dialkyl trimethylsilyl phosphites to these azadienes in the presence of acid. Depending on the steric demand of the group on nitrogen, double 1,2-addition or tandem 1,4-1,2-addition occurred.     

One-pot-synthesis of novel cinchonine-based phosphites

Cinchonine was employed as backbone for the synthesis of novel phosphite compounds with diol substituents.These monophosphinites were provided in one pot with the yields ranged from 63%to 75%.Their structures were confirmed by NMR spectroscopy and HRMS.     

Stereoselective synthesis of tetrahydropyrans via formal [4 + 2]-cycloaddition: a comparison of allylsilane and crotylsilane

The reaction of a series of beta-(triethylsilyloxy)aldehydes with several allylsilanes and crotyldimethylphenylsilane is described. Aldehydes possessing an alpha-stereocenter afforded tetrahydropyrans as mixtures of two diastereomers with allylsilane, but only a single diastereomer was observed in the case of crotylsilanes. The reaction time for crotylsilanes was longer than that for allylsilanes likely due to the increased steric hindrance. Allylsilanes afforded tetrahydropyrans in 34-67% yields, and crotylsilanes provided products in 0-62% yields.     

Reaction between naphthols and dimethyl acetylenedicarboxylate in the presence of phosphites. Synthesis of stable oxa-2 lambda 5-phosphaphenanthrenes,and benzochromene derivatives

The reaction of dimethyl acetylenedicarboxylate (DMAD) with 2-naphthol in the presence of trimethyl or triphenyl phosphite leads to stable dimethyl oxa-2 lambda 5-phosphaphenanthrene derivatives in good yields. The reaction of DMAD and trimethyl phosphite in the presence of 1-naphthol or 8-hydroxyquinoline leads to dimethyl 2-(dimethoxyphosphoryl)-3-(1-hydroxy-2-naphthyl)succinate or dimethyl 2-(dimethoxyphosphoryl)-3-(8-hydroxyquinolin-7-yl)-succinate in excellent yields. Using triethyl phosphite and DMAD in the presence of 2-naphthol or 1-naphthol produces methyl 3-oxo-2,3-dihydro-1H-benzo[f]chromene-1-carboxylate or methyl 2-oxo-3,4-dihydro-2H-benzo[h]-chromene-4-carboxylate in excellent yields.     

Transformation of alkynyl sulfones into alkynylphosphonates with trialkyl phosphites

1-Alkynylphosphonates were obtained in good to high yields by simple heating of 1-alkynyl sulfones with trialkyl phosphites.     

Trichloroisocyanuric acid-promoted thiolation of phosphites by thiols

Abstract

A simple and convenient method for the synthesis of thiophosphates by coupling of phosphites with thiols under mild conditions has been developed. The reactions were promoted by trichloroisocyanuric acid (TCCA) and were carried out at room temperature in a one-pot two-step procedure within 20?min. A variety of substrates was tolerated in this method. Notably, both aryl and alkyl thiols could afford the corresponding thiophosphates in good yields.     

A priori assessment of the stereoelectronic profile of phosphines and phosphites

This research has demonstrated the utility of a rigorously calibrated, molecular mechanics/semiempirical quantum mechanical protocol for developing stereoelectronic (Tolman) maps for phosphine ligands. A computational analysis of alkyl and aryl phosphines in common usage suggests that these ligands are quite similar stereoelectronically. A noticeable gap in the Tolman map for common phosphines is observed for large, electron-poor phosphines. Several candidates meeting these criteria were identified, the most promising of which is P(t-C(4)F(9))(3). Phosphines in which the phosphorus participates in a ring, which comprise a very small subset of reported phosphines, have very interesting stereoelectronic properties, particularly those in which the ligating phosphorus is part of a three-membered ring. In terms of steric properties, the symmetric deformation coordinate proposed by Orpen and co-workers on the basis of crystallographic studies is calculated with sufficient accuracy using PM3(tm) to allow good confidence in predictions of novel phosphines. For quantification of the electronic properties of phosphines, we analyzed changes in the CO stretching frequency upon changing the ancillary phosphine ligands.     

Organic reactions at high pressure. Wittig reaction of hindered ketones with nonstabilized ylides.

The Wittig reaction between n-butylidenetriphenylphosphorane and a series of cyclohexanones of increasing steric hindrance around the carbonyl group has been studied at 7 kbar and 15 kbar pressure (0.75–1.5 GPa) and at 40 °C. In all cases, except 2,2,6,6-tetramethylcyclohexanone and fenchone, 45-60% yields of olefins were obtained, in contrast to poor to no yields which were obtained under ambient conditions.     

The difference in reactivity of (−)-mono and dimenthyl vs. diethyl alkylphosphonates in the α-lithiation reaction: Carbanionic synthesis of unknown (−)-dimenthyl 1-iodoalkylphosphonates and their first use in the radical iodine atom transfer addition (I-ATRA) and cyclisation (I-ATRC) reactions

Unknown (−)-dimenthyl and ethyl (−)-menthyl 1-iodoethylphosphonates were synthesized via 1-lithio derivatives in 85-87% yields. Starting (−)-dimenthyl alkylphosphonates (R = Me, Et, i-Pr) were obtained in the Michaelis-Becker reaction (75-81% yields) and/or in the methylation reaction of the corresponding 1-lithio-alkylphosphonates (78-92% yields). An interesting concentration and time correlations, never observed for diethyl alkylphosphonates, were found for the metalation of bulky (−)-menthyl alkylphosphonates with n-BuLi and general reaction conditions for the carbanion generation were elaborated. The first example of the I-ATRA reaction of (−)-dimenthyl 1-iodoethylphosphonate with 1-hexene (AIBN) gave four diastereomers (1.6:1:1:0.4), separated into two pairs. The I-ATRC reaction was not effective due to a steric hindrance around the reactive center. The X-ray analysis of (−)-dimenthyl methylphosphonate confirmed a considerable steric hindrance in higher (−)-dimenthyl alkylphosphonate esters in comparison to their diethyl analogs.     

Multicomponent Synthesis of Unsymmetrical Unsaturated N‐Heterocyclic Carbene Precursors and Their Related Transition‐Metal Complexes

A low‐cost, modular, and easily scalable multicomponent procedure affording access in good yields and excellent selectivity (up to 93 %) to a wide range of (a)chiral unsymmetrical 1‐aryl‐3‐cycloalkyl‐imidazolium salts is disclosed. Electronic and steric properties of the corresponding unsymmetrical unsaturated N‐heterocyclic carbene (U₂‐NHC) ligands were evaluated and evidenced strong electron donor ability, high steric discrimination, and modular steric demand.     

Rh(I)-catalyzed reaction of 2-(chloromethyl)phenylboronic acids and alkynes leading to indenes

The reaction of 2-(chloromethyl)phenylboronic acid (1) with alkynes in the presence of a Rh(I) complex gave indene derivatives in high yields. The regioselectivity depends on the steric nature of the substituent on the alkynes. A bulky group favors the alpha-position of indenes.     

A facile synthesis of α-chloroboronic esters via the base induced reaction of α,α-dichloromethyl methyl ether with hindered borinic esters

Treatment of hindered borinic esters, R₂ BOR′; with an equimolar quantity of α,α-dichloromethyl methyl ether and lithium triethylcarboxide yields the α-chloroboronic esters, R₂ CHClB(OCH₃)OR′, in excellent yields. In cases where the steric requirements of R are not sufficient, the steric requirements of R′ can be increased to achieve the synthesis.     

Synthesis of new diverse macrocycles from diol precursors

The formation of a library of diverse macrocycles with different ring sizes from two easily accessible building blocks is presented. Reacting diol precursors with electrophilic reagents lead to 17-membered sulfites and 19-membered malonates in 34-79% yield. Double-reductive amination of dialdehyde analogs of the diol precursors leads to 15-membered amines in yields ranging from 9 to 60%, reflecting large differences in reactivity based on steric environment.     

Steric hindrance-controlled Pd(0)-catalyzed coupling-cyclization of 2,3-allenamides and organic iodides. An efficient synthesis of iminolactones and gamma-hydroxy-gamma-lactams

Under the catalysis of 1 mol % Pd(PPh3)4, the reaction of 4,4-disubstituted 2,3-allenamides and organic iodides in toluene afforded iminolactones stereospecifically in >90% yields using K2CO3 (2 equiv)-5 mol % TBAB as the base. A similar reaction with 4-monosubstituted 2,3-allenamides afforded gamma-hydroxy-gamma-lactams in relatively lower yields. The N/O-attack selectivity may be determined by the steric effect at the 4-position of 2,3-allenamides.     

Organophosphorus compounds—XIX : The reaction of trialkyl phosphites with extended p-quinones

Trimethyl and triethyl phosphites react with diphenoquinone 3, yielding 4,4′-dihydroxydiphenyl 10; 4′-alkoxy-4-biphenylyl dialkyl phosphates 5, 4,4′-biphenylylene tetraalkyl bis(phosphates), 6, and 4′-hydroxy-4-biphenylyl dialkyl phosphates 9 are also isolated in minor yields. The effect of temperature on the reaction is studied. A mechanism for the reaction is presented which accounts for the experimental results. The reaction of trimethyl and triethyl phosphites with quinoneimines 12 gives the corresponding phosphoramidates 13, in quantitative yields.     

Organoboranes for synthesis : Reaction of organoboranes with representative organic azides. A general stereospecific synthesis of secondary amines and N-substituted aziridines

Reaction of trialkylboranes with organic azides in refluxing xylene, followed by hydrolysis, leads to good yields of secondary amines. This reaction is highly dependent on the steric effects around both boron and the azide moiety. The reaction becomes much slower when the steric bulk of one of the reagents is increased and fails when both are hindered. The dialkylchloroboranes are more reactive than trialkylboranes and provide better yields of the desired secondary amines with a11 azides tested. The alkyldichloroboranes react with organic azides at temperatures between room temperature and 60°C and produce excellent yields of secondary amines. Furthermore, the stereochemistry of the original carbon-boron bond is retained. The mechanism of these reactions is discussed and the reaction applied to the synthesis of N-alkyl- and N-arylaziridines.     

Steroidal cyclobutanones

Cycloaddition of dichloroketene and 3-, 7-, 17-, and 20-methylene steroids affords the corresponding cyclobutaneones in yields reflecting the steric crowding around the reacting olefinic double bond.

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Steroid-Cyclobutaneone (Kurz Mitteilung)

Zusammenfassung Cycloaddition von Dichlorketen an 3-, 7-, 17- und 20-Methylen-Steroide ergab die jeweiligen Cyclobutanonderivate in Ausbeuten, die den sterischen Gegebenheiten rund um die reagierenden olefinischen Doppelbindungen entsprechen.

     

Preparation of bis(ω-hydroxyalkl)phosphites and polyurethanes from them

Transesterification of dimethylphosphite (DMP) with diols yields the tri-functional bis(ω-hydroxyalkyl)phosphites. Phosphorus-containing polyurethanes are obtained by adding the latter to toluene- and hexamethylenediisocyanate.     

Sulfur-mediated C(sp2)–H imidation and 1,2-imidofluorination of vinyl sulfides

A new strategy for the C(sp²)–H imidation and 1,2-imidofluorination of vinylsulfides has been established through simple treatment with N-fluorobis(benzenesulfonyl)imide, which acts as both oxidant and nitrogen source. For alkyl and electron-rich aryl vinylsulfides, alkyl/arylthioenamines are produced in up to 92% total yields. However, for steric and electron-deficient aryl vinylsulfides, 1,2-imidofluorination products are prepared in up to 73% yields. The chemoselectivity is controlled by the steric and electronic effects of aryl substituents. Thionium ions are proposed as key intermediates in the two reactions.