Diborane as a reducing agent - VI the novel reduction of indole-1-carboxaldehydes to 1-methyl- indoles,di(indolyimethyl) ethers and indolylmethyl indolines

Reduction of the indole-1-carboxaldehydes ($\text{1a}$-$\text{1f}$) with borane /THF gives the 1-methylindoles ($\text{4}$) in 42-91-% yields together with the di(indolylmethyl)ethers ($\text{8}$), the indolyl-methyl indolines ($\text{7}$), the unsymmetric ether($\text{10}$) and the indolenine ($\text{11}$) as the minor products, except $\text{7a}$. This appears to be the first report on the formation of symmetric ethers in the borane/THF reduction of an oxygen function. The formation of $\text{7a}$ and $\text{7b}$ from $\text{1a}$ and $\text{1b}$ implies that electrophilic substitution takes place primarily at position 3 of 3-substituted indoles, $\text{1c - 1f}$ did not form the corresponding $\text{7}$ probably because of steric hindrance. These results are discussed in relation to the mechanisms of borane/THF reduction, origin of the different products and electrophilic substitution in 3-substituted indoles.     

BH3 THF reduction of 3-methylisoxazolo [4,5-c]pyridines

3-Methylisoxazolo[4,5-c]pyridine $\text{1}$ on reduction with BH₃:THF gave, via the isolable complex $\text{4}$, the tetrahydroisoxazolopyridine $\text{5}$. The presence of two chlorine atoms at the 4 and 6 positions directed borane attact to the isoxazole ring, yielding the aminoethylpyridine $\text{8}$. Both types of reduction were obtained with 6-chloroisoxazolo[4,5-c]pyridine $\text{7}$.     

Backbone rearrangements of methyl (-)-kaur-9(11)-en-19-oate and its epoxide: structures of two diterpenes of a new skeletal type

cleavage of the epoxide ($\text{2}$) of methyl (-)-kaur-9(11)-en-19-oate ($\text{1b}$) with boron trifluoride-ether in benzene and in acetic anhydride yielded ($\text{3a}$) and ($\text{3b}$), respectively. On epoxidation with $\text{m}$-chloroperbenzoic acid in the presence of $\text{N}$-nitrosomethyl urea, ($\text{1b}$) suffered a backbone rearrangement to form ($\text{6}$).     

Efficient heterocyclisation via 2-aza-cope rearrangements of α-acyliminium intermediates. Formation of pyrrolizidines and somel thia-analogues

HCOOH-ring closures of OH-lactams $\text{7}$ possessing an allyl substituted alkene function solely afford pyrrolizidines $\text{8}$ and $\text{9}$ in high yield via 2-aza-Cope rearrangement and ensuing α-acyliminium cyclisation.     

Rearrangement of allyl hexafluoroisopropyl sulfides [1]

The rearrangement of terminal allylic hexafluoroisopropyl sulfides to the internal olefinic sulfide occurs under either photochemical or thermal conditions. In the case of the formation of $\text{E}$ and $\text{Z}$ isomers, the $\text{E}$ isomer was predominant. The rearrangement is suggested as a unimolecular, associative radical mechanism, $\text{via}$ kinetic studies, use of inhibitors, or radical initiator.     

Acetoxyphenylketene. Reaction with biacetyl

The generation of acetoxyphenylketene (4) in the cold in the presence of biacetyl yields the single β-lactone $\text{12B}$, which undergoes a novel rearrangement to the tricyclic orthoester lactone $\text{11}$ above 130°.     

HMPA-Mediated conjugate addition of alkyl- and phenylthioallyl anions to cyclopentenone

One equivalent of HMPA induces 1,4-addition of the title anions predominantly through the $\text{α}$-position to cyclopentenone in THF at ?78°. In THF alone irreversible addition takes place to give mixtures comprising largely $\text{α}$ and $\text{γ}$-1,2 products.     

A highly efficient and general N-monomethylation of functionalized primary amines via formylation--borane:methyl sulfide reduction

Formylation of functionalized primary aromatic and aliphatic amines with acetic formic anhydride (AFA) followed by borane:methyl sulfide reduction in the same pot affords the corresponding $\text{N}$-methylamines in excellent isolated yields, uncontaminated bybis alkylation; the reaction sequence is applicable to even very weakly basic and sterically hindered amines.     

Studies on organophosphorus compounds XLVII preparation of thiated synthons of amides,lactams and imides by use of some new p,s-containing reagents

The thionation properties of 2,4-bismethylthio-1,3,2,4-dithiadiphosphetane 2,4-disulfide, $\text{1}$, 2,4-bis(4-phen-oxyphenyl)-1,3,2,4-dithiaphosphetan is that $\text{2}$, $\text{3}$ and thionate most amides and lactams In THF at room temperature (reaction time 5 min) to give the corresponding thionated compounds. Imides are easily thionated by $\text{2}$, $\text{3}$ and $\text{4}$ In DME at 60 °C. The reactions of $\text{1}$ with amides, imides and most lactams are run at 60°C to give good yields of the corresponding thionated compounds.     

An approach to the enantiocontrolled synthesis of pseudomonic acids via a novel mono—claisen rearrangement

A short, efficient approach to a key chiral intermediate for the synthesis of pseudomonic acids A and C is delineated.Pseudomonic acids A($\text{1a}$), B($\text{1b}$), and C($\text{2}$) are members of a novel of “C-glycopyranoside” antimicrobial agents which have recently attracted synthetic attetion.² Presently, we wish to report a short efficient stratedy towards the total synthesis of opticaly active pseudomonic acids. The sequence is highlighted by a novel controlled mono-Claisen rearrangement and a highly regioselective π-allylpalladium mediated displacement.Diacetyl-(L)-arabinal ($\text{3}$)³ was converted to the bis-ketenesilylacetal $\text{4}$ and warmed to 60°C according to the Ireland ester-enolate Claisen rearrangement method.⁴ Over a period of ≈5h, smooth conversion to a major rearranged product $\text{5}$ was observed by 300 MHz NMR. The identity of $\text{5}$ was confirmed by direct desilylation and methylation (KF, KHCO₃, H₂O, HMPA, CH₃I). After flash chromatography, compound $\text{7}$ was isolated in 55% overall yield from $\text{3}$. Careful inspection of the crude methylation product revealed the presence of ≈5% doubly rearranged product $\text{6}$.The rearrangement of $\text{4}$ to $\text{5}$ is a unique example of a selective mono-Claisen rearrangement in which the rate of a second similar Claisen rearrangement ($\text{5}$ → $\text{6}$) is much slower under the reaction conditions. Although the reasons for this interesting selectivity are unclear at this time,⁵ in practice, the mono-Claisen rearrangement obviates the need for selective differentiation of the two hydroxyl groups, a difficult task at best, in this case.Palladium mediated allylic acetate displacement provided an ideal method for introduction of a second chemodifferentiated side chain with allylic retention and retention of stereochemistry. Alkylation of $\text{7}$ with sodiothylmalonate using 5 mole % Pd(O)dppe₂⁶ was unusually facile (<45 min, 25°C, THF). After semi-preparative HPLC, essentially a single regio- and stereoisomer was isolated in 96% yield.⁷ Structure $\text{8}$ was confirmed by extensive ¹H-NMR decoupling, as well as an off-resonance ¹³C-NMR experiment. In particular, H₁ (δ 4.53) was coupled vicinally to H₆ and H₆′ (5 Hz, 8 Hz) and H₂ (1.5 Hz), and allylically to H₃ (2 Hz). In contrast, H₄ (δ 2.78) was coupled to H₇ (10 Hz), H_5e and H_5a (1.8 Hz, 4 Hz), H₃ (5 Hz), and H₂ (<1 Hz). In addition, H₁ and H₄ exhibited a small long range coupling constant (J = <1 Hz). The coupling constants rule out

regioisomer $\text{9}$ and are fully consistent with the indicated conformation, which minimizes 1,3-diaxial-like interactions.Finally, catalytic osmylation of $\text{8}{}^8$ gave a single cis-diol $\text{10}$ in nearly quantitative yield. Appending of suitably functionalized side chains to provide an enantiocontrolled synthesis of pseudomonic acids A($\text{1a}$) and C($\text{2}$) is in progress.^9,10     

Preparation of alcohols from sulfones and trialkylboranes

The reaction of sulfone anions with trialkylboranes followed by thermal isomerization of the obtained boron compounds in the presence of excess borane-methyl sulfide complex and by alkaline hydroperoxide oxidation yields primary alcohols.     

The stereochemistry of the hydroboration rearrangement.

Hydroboration of 1,2-dimethylcyclopentene with BH₃·THF affords a product in which boron migrates $\text{stereospecifically}$ at low temperature into the cyclopentane ring. At higher temperatures subsequent (non-stereospecific) isomerisation occurs via a competing reaction mechanism.     

Stereospecific preparation of 1,2-epoxyalkyllithium reagents via the generalized lithiation of a-heterosubstituted epoxides1

A variety of α-heterosubstituted epoxides bearing triphenylsilyl, trimethylsilyl, diethoxyphosphinyl, phenylsulfonyl, phenyl, ethoxycarbonyl and cyano groups was found to undergo stereospecific α-lithiation by use of such bases as $\text{n}$-butyllithium, $\text{t}$-butyllithium or lithium diisopropylamide in solvent combinations of hexane with THF, ethyl ether or TMEDA at temperatures ranging from ?78° to ?110°C. The formation and stereochemistry of the resulting1,2-epoxyalkyllithium reagents were ascertained by quenching with deuterium oxide, methyl iodide or chloro(trimethyl)silane and analyzing the NMR spectra of the products isolated in 50–100% yields.     

Studies in azide chemistry. Part 12. One-pot conversion of 4-azidotetrafluoropyridine to 1,3,4-trifluoro-7,9-dimethyl-11H-pyrido[4,3-c]benzo[1,2]diazepine

Thermolysis of 4-azidotetrafluoropyridine in the presence of an excess of mesidine at 170 °C yields tetrafluoro-4-(2,4,6-trimethylphenylazo)- pyridine, which undergoes intramolecular dehydrofluorination $\text{in situ}$ to provide 1,3,4-trifluoro-7,9-dimethyl-11$\text{H}$-pyrido[4,3-$\text{c}$]benzo[1,2]diazepine.     

Photodecomposition of selenosulfonates and their facile photoaddition to alkenes 1

Phenyl areneselenosulfonates ($\text{1}$) are very photosensitive and easily undergo photodecomposition via initial homolysis of the SeS bond. In the presence alkenes this facile photodissociation of $\text{1}$ can be used to initiate a free radical chain reaction (eq 6) that leads to addition of $\text{1}$ to the alkene to form β-phenylselenosulfones ($\text{2}$). The photoaddition requires much shorter reaction times than the non-photolytic addition of $\text{1}$ to alkenes described recently.²     

Substituent directive effects in 1,2-benzodiazepine synthesis via electrocyclic aromatic substitution by the diazo-group: a rearrangement of 9- to 7-substituted 3H-1,2-benzodiazepines

The directive effect of aryl-substituents on the site of ring closure in the electrocyclisation of 1-aryl-3-diazoalkenes has been investigated. At 80°C the product ratio is determined by kinetic control but for some substituents the kinetically favoured 9-substituted 3$\text{H}$-1,2-benzodiazepines undergo a new rearrangement to their more stable 7-substituted isomers.     

Synthesis of bromodifluoromethyl phenyl sulfide,sulfoxide and sulfone [1]

Sodium thiophenoxide reacts with dibromodifluoromethane to give bromodifluoromethyl phenyl sulfide. Peracid oxidation of the sulfide gives the corresponding sulfoxide and sulfone. The formation of the sulfide is suggested to proceed $\text{via}$ attack of thiophenoxide on halogen to produce difluorocarbene. Capture of carbene by thiophenoxide followed by a second positive halogen abstraction reaction yields the sulfide, PhSCF₂Br. The use of excess sodium thiophenoxide yields difluorobis(thiophenyl)methane, (PhS)₂CF₂, $\text{via}$ a similar mechanistic scheme.     

Molecular rearrangements of 5-azido substituted 1,2,3-triazoles

5-Azido-4-methoxycarbonyl-1-phenyl-1,2,3-triazole ($\text{8a}$) and its phenyl substituted derivatives $\text{8b}$,$\text{c}$ rearrange at 60–80°C to give tetrazolyldiazoacetates $\text{9}$, which have been isolated. When the reactions are allowed to go to completion, products derived from the diazo compounds are obtained; i.e. norcaradienes ($\text{10}$) from benzene solutions and imidazotetrazoles ($\text{12}$) from nitrite solutions. The latter decompose photochemically into diazacyclopentadienonimines ($\text{13}$). A kinetic study of the rearrangement $\text{8}$ → $\text{9}$ has been carried out and the mechanism (Scheme VI) is discussed in comparison with the Dimroth rearrangement.