Ring cleavage reactions of methyl α-D-allopyranoside derivatives with phenylboron dichloride and triethylsilane

In the course of our studies on the regioselective carbon-oxygen bond cleavage of the benzylidene acetal group of hexopyranosides with a reducing agent, we found that a combination of a Lewis acid and a reducing agent triggered a ring-opening reaction of the pyranose ring of methyl α-D-allopyranosides. The formation of an acyclic boronate ester by the attachment of a hydride ion at C-1 indicated that the unexpected endocyclic cleavage of the bond between the anomeric carbon atom and the pyranose ring oxygen atom proceeded via an oxacarbenium ion intermediate produced by the chelation between O5/O6 of the pyranoside and the Lewis acid, followed by nucleophile substitution with a hydride ion at C1.     

硅杂四元环化合物的合成和反应

硅杂四元环化合物在有机硅化学中是一类非常重要的小分子环系化合物, 广泛应用于有机化学、金属有机化学以及材料化学. 环上只含有一个硅原子的硅杂环丁烷可以通过γ-卤代丙基硅烷的Grignard反应、Si＝C键与烯烃的 [2＋2]环加成反应以及硅杂环丙烷的扩环反应合成, 环上只含有一个硅原子的硅杂环丁烯可以通过格氏试剂或锂试剂参与的Si—C键的关环反应、硅杂环丁烷的转化反应、硅卡宾对C—H键的插入反应、Si＝C键与炔烃的[2＋2]环加成反应以及二炔基硅烷的分子内成环反应等途径合成. 硅杂环丁烷和硅杂环丁烯由于存在环张力和具有一定的Lewis酸性, 能够通过扩环反应生成五元和六元含硅杂环化合物, 也能够通过开环反应生成不同结构的有机硅分子和聚合物, 抑或实现有机反应在温和条件下的转化.     

A Phosphinine-Derived 1-Phospha-7-Bora-Norbornadiene: Frustrated Lewis Pair Type Activation of Triple Bonds

Salt metathesis of 1-methyl-2,4,6-triphenylphosphacyclohexadienyl lithium and chlorobis(pentafluorophenyl)borane affords a 1-phospha-7-bora-norbornadiene derivative 2 . The C≡N triple bonds of nitriles insert into the P−B bond of 2 with concomitant C−B bond cleavage, whereas the C≡C bonds of phenylacetylenes react with 2 to form λ⁴-phosphabarrelenes. Even though 2 must formally be regarded as a classical Lewis adduct, the C≡N and C≡C activation processes observed (and the mild conditions under which they occur) are reminiscent of the reactivity of frustrated Lewis pairs. Indeed, NMR and computational studies give insight into the mechanism of the reactions and reveal the labile nature of the phosphorus–boron bond in 2 , which is also suggested by detailed NMR spectroscopic studies on this compound. Nitrile insertion is thus preceded by ring opening of the bicycle of 2 through P−B bond splitting with a low energy barrier. By contrast, the reaction with alkynes involves formation of a reactive zwitterionic methylphosphininium borate intermediate, which readily undergoes alkyne 1,4-addition.     

Stereoselective synthesis of piperidinone and quinolinone systems via ring opening reactions using TiCl4/silyl reagents

Titanium(IV) chloride and silyl reagents mediated regio- and chemoselective ring opening reactions of oxa-bridged piperidinone ring systems were demonstrated. This methodology interestingly undergoes the stereoselective ring opening at the C-O bond of oxa-bridged piperidinone ring systems. Study of TiCl₄ with hydride or non-hydride silyl reagents furnished the product with selectivity. This protocol is highly valuable to synthesize a range of stereoselective piperidinones, quinolinones ring systems.     

Reaction of B2(o‐tol)4 with CO and Isocyanides: Cleavage of the C≡O Triple Bond and Direct C−H Borylations

The reaction of highly Lewis acidic tetra(o‐tolyl)diborane(4) with CO afforded a mixture of boraindane and boroxine by the cleavage of the C≡O triple bond. ¹³C labeling experiments confirmed that the carbon atom in the boraindane stems from CO. Simultaneously, formation of boroxine 3 could be considered as borylene transfer to capture the oxygen atom from CO. The reaction of diborane(4) with ^tBu?NC afforded an azaallene, while the reaction with Xyl?NC furnished cyclic compounds by direct C?H borylations.     

Stereochemical studies, 88. Saturated heterocycles, 83: Synthesis of stereoisomeric condensed-skeleton 2-imino-substituted 1,3-oxazines

Thiourea ( - , - ) and urea ( - , - ) derivatives have been prepared from - and -2-aminomethyl-1-cyclopentanols, and -l-cyclohexanols and their -methyl derivatives with phenyl isothiocyanate and phenyl isocyanate, respectively. Treatment of and with methyl iodide and then with alkali furnished - with the exception of the - -methyl derivative - 2-phenylimino-1,3-oxazines ( , , - ). The remarkable fact that the ring closure of -2-amino-methyl-1-cyclopentanols gives 1,3-heterocycles with -anellation supports the assumption that the -1,2-disubstituted-1,3-difunctional cyclopentanes undergo ring closure when 1,3-heterocycles with a delocalized pπ bond system are formed. With thionyl chloride the -urea derivatives - afforded an elimination product ( ), whereas the isomers yielded the oxazines by inversion. ¹H and ¹³C NMR spectroscopic studies indicated that in - , the “O-in” conformers are favoured (the methylene group of the hetero ring is , while the oxygen atom is ) and all 3-unsubstituted-2-phenylimino-1,3-oxazines exist exclusively in the tautomeric form with an C=N bond.     

Regio- and Stereoselective Formation of 1,3-Oxathiolanes by Reactions of Thiocarbonyl Compounds with Oxiranes

Abstract

Lewis acid-catalyzed reactions of oxiranes with a variety of C═S compounds yield 1,3-oxathiolanes. The ring enlargement of monosubstituted oxiranes occurs regioselectively via cleavage of the O,C(3) bond of alkyl substituted oxiranes and the O,C(2) bond of phenyl oxirane. Furthermore, the reaction proceeds with inversion of the configuration at the center of the nucleophilic attack by the S-atom. The formation of thiocarbonylium ions as intermediates is supported by Wagner–Meerwein-type rearrangements. Enolized thioketones react with oxiranes to give enesulfanyl alcohols, which undergo an acid-catalyzed cyclization to yield 1,3-oxathiolanes.     

Zinc triflate-catalyzed intermolecular hydroamination of vinylarenes and anilines: scopes and limitations

Intermolecular hydroamination of vinylarenes and anilines was studied using zinc triflate as catalyst. NMR experiments supported a Lewis acid activation of the CC double bond. Electronic/steric effect study indicated that Lewis acidity of the catalyst as well as the coordination property of the amine were the governing factors for successful hydroamination of the substrates. More nucleophilic amine would bind more tightly to the central metal, leading to an unproductive coordination. Approach of bulky amine to CC bond would be hindered, and an alternative electrophilic substitution on benzene ring of the amine would become the major reaction. Electrophilic substitution would become predominant when strong electron-donating group is presented on aniline benzene ring.     

Alumazene adducts with pyridines: synthesis, structure, and stability studies

Lewis acid-base adducts of the alumazene [2,6-(i-Pr)2C6H3NAlMe]3 (1) with pyridine (py) and 4-dimethylaminopyridine (dmap) were synthesized and structurally characterized: 1(py)2 (2), 1(py)3 (3), 1(dmap)2 (4), and 1(py)(dmap) (5). The bisadducts 2, 4, and 5 form the trans isomers. The trisadduct 3 exhibits an unexpected cis-cis isomer and can be prepared only in the presence of excess py. The planarity of the alumazene ring is lost upon coordination of the Lewis base molecules. A comparison of the Al-N(base) bond distances and pyramidality at Al suggests the higher basicity of dmap. NMR spectroscopy confirms stability to dissociation of the bisadducts in solution while the trisadduct 3 is labile and converts to 2. The thermodynamics of the adduct formation has been investigated experimentally and theoretically. Thermodynamic characteristics of the 1(py)n (n=2, 3) dissociation reactions in the temperature range 25-200 degrees C have been derived from the vapor pressure-temperature dependence measurements by the static tensimetric method. In all experiments, excess py was employed. Quantum chemical computations at the B3LYP/6-31G* level of theory have been performed for the 1(py)n and model complexes [HAlNH]3(py)n (n=1-3). Obtained results indicate that for the gas phase adducts upon increasing the number of py ligands the donor-acceptor Al-N(py) distance increases in accord with decreasing donor-acceptor bond dissociation energies.     

Total synthesis of brevetoxin B

The convergent total synthesis of brevetoxin B (1) has been achieved. The intramolecular allylation of the O,S-acetal 20, prepared from the alpha-chlorosulfide 17 and the alcohol 5, was carried out using AgOTf as a Lewis acid to give the diene 21, predominantly. Ring-closing metathesis of 21 with the Grubbs catalyst 23 afforded the hexacyclic ether 25 which was converted to the A-G ring segment 2 through several steps. The intramolecular allylation of the alpha-acetoxy ether 42, prepared from 2 and the J-K ring segment 3, followed by ring-closing metathesis provided the polycyclic ether framework 44. A series of reactions of 44, including oxidation of the A ring, deprotection of the silyl ethers, and selective oxidation of the resulting allylic alcohol, furnished 1.     

Titanium tetrachloride mediated reductive ring opening of C-aryl pseudoglycals

A facile reductive ring opening of C-aryl pseudoglycals is reported for the first time. The combination of titanium tetrachloride (Lewis acid) and triethylsilane (reducing agent) at −78 °C in dichloromethane is a mild and efficient reagent system for this transformation. The reagent system was successfully tested on various C-aryl pseudoglycal substrates to yield the corresponding ring opened products containing two asymmetric hydroxyls and a cis-double bond.     

1,4-Zwitterionic intermediates formed by cleavage of a cyclobutane ring and their cycloaddition reactions

Cycloaddition reaction is an efficient organic reaction because all of the substrate components are introduced into a product skeleton. Recently, more than six-membered rings have been synthesized by Lewis acid-promoted ring cleavage of a cyclobutane ring followed by addition to an unsaturated bond. Typical examples in the literature of these types of reactions using 1-donor–2-acceptor cyclobutanes and 3-donor cyclobutanones with Lewis acids are presented in this Letter.     

Regioselective ring opening of alkylidenecyclopropanone silyl acetals

Alkylidenecyclopropanone silyl acetals are readily available from the reaction of an alkylidenemethyliodonium salt and ketene silyl acetals in the presence of triethylamine. The three different C-C bonds of the cyclopropane ring can be selectively cleaved with HCl, Lewis acid, or fluoride. The alkylideneallyl cation formed via the cleavage of C2-C3 bond with Lewis acids shows further selectivity in reacting with a nucleophile.     

Al/P- and Ga/P-Based Frustrated Lewis Pairs and Electronically Unsaturated Substrates: Ring Cleavage and Ring Closure,C−C and C−N Bond Formation

Al/P- and Ga/P-based frustrated Lewis pairs (FLPs) reacted with an azirine under mild conditions under cleavage of the heterocycle on two different positions. Opening of the C−C bond yielded an unusual nitrile–ylide adduct in which a C−N moiety coordinated to the FLP backbone. Cleavage of a C−N bond afforded the thermodynamically favored enamine adduct with the N atom bound to P and Al or Ga atoms. Ring closure was observed upon treatment of an Al/P FLP with electronically unsaturated substrates (4-(1-cyclohexenyl)-1-aza-but-1-en-3-ynes) and yielded by C−N bond formation hexahydroquinoline derivatives, which coordinated to the FLP through P−C and Al−C bonds. Diphenylcyclopropenone showed a diverse reactivity, which depending on steric shielding and the polarizing effect of Al or Ga atoms afforded different products. An AltBu₂/P FLP yielded an adduct with the C=O group coordinated to P and Al. The dineopentyl derivative gave an equilibrium mixture consisting of a similar product and a simple adduct with O bound to Al and a three-coordinate P atom. Both compounds co-crystallize. The Ga/P FLP only formed the simple adduct with the same substrate. Rearrangement resulted in all cases in C₃-ring cleavage and migration of a mesityl group from P to a former ring C atom by C−C bond formation. Diphenylthiocyclopropenone (evidence for the presence of P=C bonds) and an imine derivative afforded similar products.     

Total Synthesis of 1‐Hydroxytaxinine

1‐Hydroxytaxinine ( 1 ) is a cytotoxic taxane diterpenoid. Its central eight‐membered B‐ring possesses four oxygen‐functionalized centers (C1, C2, C9, and C10) and two quaternary carbon centers (C8 and C15), and is fused with six‐membered A‐ and C‐rings. The densely functionalized and intricately fused structure of 1 makes it a highly challenging synthetic target. Reported here is an efficient radical‐based strategy for assembling 1 from A‐ and C‐ring fragments. The A‐ring bearing an α‐alkoxyacyl telluride moiety underwent intermolecular coupling with the C‐ring fragment by a Et₃B/O₂‐promoted decarbonylative radical formation. After construction of the C8‐quaternary stereocenter, a pinacol coupling reaction using a low‐valent titanium reagent formed the B‐ring with stereoselective installation of the C1,C2‐diol. Subsequent manipulations at the A‐ and C‐rings furnished 1 in 26 total steps.     

Effect of Through‐Bond Interaction on Conformation and Structure in Rod‐Shaped Donor–Acceptor Systems. Part 2.

The crystal structures of seven N‐aryltropan‐3‐one (=8‐aryl‐8‐azabicyclo[3.2.1]octan‐3‐one) derivatives 1T1, 2T1, 2T2, 3T2, 5T2, 2T3 , and 3T3 are presented (Fig. 2 and Tables 1–5) and discussed together with the derivatives 1T2 and 4T2 published previously. The piperidine ring adopts a chair conformation. In all structures, the aryl group is in the axial position, with the plane through the aryl C‐atoms nearly perpendicular to the mirror plane of the piperidine ring. The through‐bond interaction between the piperidine ring N‐atom (one‐electron donor) and the substituted exocyclic C?C bond (acceptor) not only elongates the central C? C bonds of the piperidine ring but also increases the pyrimidalization at C(4) of the piperidine ring. Flattening of the C(2)–C(6) part of the piperidine ring decreases the through‐bond interaction.     

Kinetics and mechanism for CO(2) scrambling in a N-carboxyimidazolidone analogue for N(1)-carboxybiotin

The N-carboxyimidazolidone anion, 2(-), was prepared as an analogue for N(1)-carboxybiotin, and the kinetics of its CO(2)-dependent chemistry were studied in polar aprotic media. The objective was to assess the viability of unimolecular CO(2) elimination from N(1)-carboxybiotin as a microscopic step in biotin-dependent carboxyl transfer enzymes. The anionic 2(-) was prepared as its lithium salt by first deprotonating 2-imidazolidone with phenyllithium, followed by direct reaction with carbon dioxide. This procedure also permitted isolation of the (13)C enriched derivative 2(-)[(13)C] by reaction with (13)CO(2). Proton and (13)C NMR and isotope-dependent FTIR measurements confirmed that carboxylation had occurred at the nitrogen atom of 2-imidazolidone to give 2(-). Time-dependent FTIR spectroscopy showed that Li2 undergoes carboxyl exchange with free carbon dioxide, with kinetics indicative of rate-limiting unimolecular dissociation of the N-CO(2) bond. Under these conditions, the weak Lewis acid Mg(2+) catalyses the exchange of 2(-) with free CO(2), which appears to be related to the ability of the metal ion to coordinate to 2(-). Reaction of Li2 with carboxylic acids in DMSO results in acid-dependent decarboxylation of 2(-) with a rate that is dependent on the concentration of the acid and its pK(a). A common mechanistic framework is presented for both Lewis acid catalyzed carboxyl exchange and acid-dependent decarboxylation that involves initial interaction at the carbonyl oxygen and which has the effect of polarizing the nitrogen lone pair toward the imidazolidone ring rather than the carboxyl group. Lewis acid interaction with the carbonyl oxygen thus weakens the N-CO(2)(-) bond and functions as a trigger for dissociation of CO(2). In the context of biotin-dependent enzymes, this suggests a means by which the kinetically stable N(1)-carboxybiotin cofactor intermediate might be triggered for dissociation of CO(2).     

A facile synthesis of natural products chaetomellic acid A and 1,7(Z)- nonadecadiene-2,3-dicarboxylic acid

Synthesis of recently isolated bioactive natural products chaetomellic acid A anhydride (1) and a novel 1,7(Z)-nonadecadiene-2,3-dicarboxylic acid (2) have been described. Chemoselective carbon[bond]carbon S(N)2' coupling reactions of appropriate Grignard reagents with dimethyl bromomethylfumarate (7) in diethyl ether in the presence of HMPA at room temperature furnished the corresponding diesters 8 and 15 in 60-62% yields. The formed diesters 8 and 15 on hydrolysis gave respectively the corresponding desired diacids 9 and 2 in quantitative yields. Acetic anhydride induced ring closure of diacids 9 and 2 respectively gave the chaetomellic acid A anhydride (1) and isochaetomellic acid B anhydride (16) with 38-39% overall yields in five steps.     

Rhodium-catalyzed cyclization of 1,6-enynes triggered by addition of arylboronic acids

1,6-Enynes reacted with arylboronic acids in the presence of a catalytic amount of a rhodium(I) complex under mild conditions to give (Z)-1-(1-arylethylidene)-2-vinylcyclopentanes. The regioselective addition of an arylrhodium(I) species across the carbon-carbon triple bond triggered the cyclization process. Intramolecular carborhodation onto the pendent alkene in a 5-exo mode furnished a five-membered ring. Finally, the rhodium(I) methoxide generated by beta-methoxy elimination reacted with the arylboronic acid to promote the next catalytic cycle.     

A comparison of crystallographic and NMR data for thieno[2,3‐b:4,5‐b′]dipyridine and its monohydroperchlorate salt

X‐ray crystallographic studies of thieno[2,3‐b:4,5‐b′]dipyridine ( 1 ) and its monohydroperchlorate salt ( 1a ) show that 1 is protonated at N1 in ring A and not at N6 in ring C. In each compound individual rings are planar, but there is a small dihedral angle‐of‐twist between the A and C rings. On going from 1 to 1a the largest changes in bond angles and bond lengths occur in ring A. ¹H and ^l3C nmr spectra of 1 plus the ¹³C nmr spectrum of 1a are reported.