The hydroboration of 3-butenyl derivatives with 9-borabicyclo[3.3.1]nonane

The hydroboration of 3-butenyl derivatives, CH₂CHCH₂CH₂X where X represents OH, OMe, OAc, Cl, as well as the related carboxylic ester, CH₂CHCH₂COOEt, and the nitrile CH₂CHCH₂CN, with 9-borabicyclo[3.3.1]nonane (9-BBN) proceeds with remarkably high regio-selectivity. The boron is placed essentially on the terminal carbon (?98%), yielding stable organoboranes which can be readily oxidized to alcohols or subjected to other reactions. The yields of alcohols in the hydroboration-oxidation procedure are satisfactory, in the range of 82–99%. The hydroxy group liberates hydrogen rapidly and quantitatively but no further reaction is observed and hydroboration of the carboncarbon double bond then proceeds normally. The chloro and methoxy groups are not affected by 9-BBN, whereas, the ester and nitrile groups are slightly (1.5–4.0%) reduced by the reagent at 25°C. Even this small amount of reduction can be circumvented or minimized by carrying out the hydroboration at 0°C. Although this procedure requires somewhat longer reaction times, the products are cleaner and the yields are higher.     

Unique stereochemistry of 3-borabicyclo[3.3.1]nonane derivatives

The conformational equilibrium in solution was examined by NMR spectroscopy for a series of 7-phenyl-3-borabicyclo[3.3.1]nonane derivatives containing various substituents at the boron atom. The structures of these derivatives were studied in the crystalline state (X-ray diffraction analysis) and by quantum-chemical calculations (B3Pw91/6-31G*). The B...Ph transannular interactions corresponding to charge transfer from the system of the phenyl group to the vacant p-orbital of the B atom were demonstrated to be responsible for unique stability of the chair-chair conformation of these derivatives.Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1884–1896, September, 2004.     

Conformational analysis of 3-borabicyclo[3.3.1]nonane derivatives

Conformations of 3-borabicyclo[3.3.1]nonane derivatives have been studied by means of ¹H and ¹³C NMR spectroscopy. With the aid of the coupling constants ³J(HH) and ¹³C chemical shifts it has been shown that all the derivatives of 3-borabicyclo[3.3.1]nonane with the trigonal boron atom studied are in a flattened double-chair conformation. In 3-borabicyclo[3.3.1]nonane derivatives with the tetra-coordinated boron atom and substituents at the 7α-position, the chair-boat conformation predominates, the boat conformation being characteristic of the cyclohexane ring; exceptions are the compounds with the internal donor—acceptor bond between the boron atom an 7α-substituent.     

Palladium-catalyzed cross-coupling of B-benzyl-9-borabicyclo[3.3.1]nonane to furnish methylene-linked biaryls

[reaction: see text] Benzylboranes are noticeably uncommon partners within Suzuki-Miyaura coupling reactions. B-Benzyl-9-BBN was successfully coupled to a range of aryl/heteroaryl bromides, chlorides, and triflates to give pharmacologically important methylene-linked biaryl structures. Activated, deactivated, and sterically hindered substrates were successfully coupled in high yield using Pd(PPh(3))(4) or Pd(OAc)(2) with SPhos as the catalyst system.     

Facile and convenient synthesis of B-amino-9-borabicyclo[3.3.1]nonanes. Aminoboration of lsocyanates

The reaction of 9-borabicyclo[3.3.1]nonane (9-BBN) with aliphatic and aromatic primary and secondary amines in tetrahydrofuran (THF) at 65°C proceeds rapidly and quantitatively with evolution of hydrogen and the formation of the corresponding B-amino-9-borabicyclo[3.3.1] nonane (B-amino-9-BBN). Simple evaporation of THF from the reaction mixture gives the B-amino-9-BBN derivatives in high yield and purity. These B-amino-9-BBN derivatives are reactive towards alkyl and aryl isocyanates. Consequently, the aminoboration of various isocyanates has been studied using B-phenylamino-9-BBN. Thus, two equivalents of isocyanates react with one equivalent of B-phenylamino-9-BBN to afford, following the hydrolysis of the intermediate with ethanolamine, N, N'-disubstituted-N -(phenylamido)-ureas in excellent yields. A plausible mechanism for this aminoboration reaction of isocyanates is also presented.     

One-pot conversion of carboxylic acids to aldehydes through treatment of acyloxy-9-borabicyclo[3.3.1]nonanes with lithium 9-boratabicyclo[3.3.1]nonane

Carboxylic acids are readily reduced to the corresponding aldehydes in high yields by treatment of acyloxy-9-borabicyclo[3.3.1]nonanes with lithium 9-boratabicyclo[3.3.1]nonane (Li 9-BBNH) at room temperature.     

The reaction of B-alkyl-9-borabicyclo[3.3.1]nonanes with aldehydes and ketones. A facile elimination of the alkyl group by aldehydes

Certain B-alkyl-9-borabicyclo[3.3.1]nonanes (9-BBN) reduce benzaldehyde to benzyl alcohol under exceptionally mild conditions. Factors which contribute to a high rate of reaction include: an increase in the degree of substitution at the position β to the boron (isobutyl > 1-butyl >> ethyl), the ability of the alkyl group to form a syn-planar B—C—C—H conformation (cyclopentyl ? norbornyl > sec-butyl >> cyclohexyl), and the presence of an electron-withdrawing para-substituent on the benzaldehyde (p-Cl > p-H > p-CH₃O). The B-alkyl group is transformed into an olefin as the benzaldehyde is reduced. Elimination takes place predominantly if not exclusively towards the more highly substituted β hydrogen. The reaction obeys second order kinetics. The observations are consistent with a cyclic mechanism rather than a dehydroboration-reduction pathway.     

Conformational behavior of 3-borabicyclo[3.3.1]nonanes: 1. Study of molecular dynamics in 3-methoxy-7α-phenyl-1,5-dimethyl-3-borabicyclo[3.3.1]nonane

3-Methoxy-7α-phenyl-1,5-dimethyl-3-borabicyclo[3.3.1]nonane 5 in solution at room temperature exists in the double chair conformation, as shown by NMR studies. Increasing the temperature leads to an increase in the population of the chair–boat conformation. At decreased temperature hindered rotation around the B---O bond is observed for 5. Dissolving 5 in deuteropyridine leads to the reversible formation of complex 6, which exists in the chair–boat conformation. The chair–boat conformation is also the most stable one for chelate compound 7 with a tetracoordinated boron atom.     

Organoboron compounds : CCCXCIX. The matteson-pasto rearrangement in the series of 3-borabicyclo[3.3.1]nonane compounds

Bromination of 3-isopropyl-7-methyl- and 3-isopropyl-7-bromomethyl-3-borabicyclo[3.3.1]nonane leads to corresponding 3-(2-bromo-2-propyl) derivatives, which, on treatment with alcohols or pyridine as well as on heating, undergo the Matteson-Pasto rearrangement to convert into 3-X-4,4,8-trimethyl- and 3-X-4,4-dimethyl-8-bromomethyl-3-borabicyclo[4.3.1]decane (X = Br, OR). Interaction between triethylamine and 3-(2-bromo-2-propyl)-7-methyl-3-borabicyclo[3.3.1]nonane is accompanied by dehydrobromination leading to 3-isopropenyl-7-methyl-3-borabicyclo[3.3.1]nonane. Carbonylation of 3,4,4,8-tetramethyl-3-borabicyclo[4.3.1]decane at 140°C is accompanied by migration of two alkyl groups from the boron to the carbon atom, and subsequent oxidation with H₂O₂ produces 1-(2-hydroxy-2-methyl-1-propyl)-3-acetonyl-5-methyl-cyclohexane. Under more forcing conditions (180-195°C), the third alkyl group also migrates to give, after oxidation, a mixture of isomeric 3,4,4,8-tetramethylbicyclo[4.3.1]decan-3-ols. 3-n-Butoxy-4,4-dimethyl-8-bromomethyl-3-borabicyclo[4.3.1]decane, on treatment with Lì, undergoes cyclization to afford 4,4-dimethyl-3-borahomoadamantane, carbonylation and subsequent oxidation of which gave 4,4-dimethylhomoadamantan-3-ol.     

Two-Dimensional Chromatographic Analysis of Polystyrene-block-poly(methyl methacrylate) Copolymers Synthesized by Selective Oxidation of Polystrene-9-borabicyclo[3.3.1]nonane

Summary: The preparation of polystyrene block methyl methacrylate copolymers (PS-b-PMMA) is described. The polystyrene segment was prepared by anionic polymerization and the methylmethacrylate segment was prepared via free radical autoxidation of a borane agent attached to the styrene chain. 1 The chemistry involves a transformation of the anionic polymerization process to borane chemistry by firstly producing polystyrene with chain end unsaturated alkyl functional groups prepared using a n-butyllithium initiator and termination with allylchlorodimethylsilane. Secondly, the unsaturated macroinitiator end was hydroborated by 9-borabicyclo[3.3.1]nonane (9-BBN) to produce a borane terminated PS. Thirdly, the borane group at the chain end was selectively oxidized and converted to polymeric radicals in the presence of methyl methacrylate which then initiated radical polymerization to produce block copolymers. The polymer obtained was characterized using several chromatographic techniques including LC-CC (liquid chromatography under critical conditions) for the polystyrene segments and two-dimensional chromatography with LC-CC in the first dimension and SEC in the second. The results show that block formation was successful although significant homopolymerization of methyl methacrylate is also obtained.     

3-Azabicyclo[3.3.1]nonane Derivatives: IV. Synthesis of Amino Acids with 3-Azabicyclo[3.3.1]nonane Fragment

A series of 1.5-dinitro-3-azabicyclo[3.3.1]non-6-enes was prepared by reduction of 1-R-2,4- and 1-R-3,5-dinitrobenzenes with potassium borohydride followed by Mannich reaction with formaldehyde and amino acids. The molecular structure of (6-bromo-1,5-dinitro-3-azabicyclo[3.3.1]non-6-en-3-yl)acetic acid was studied by X-ray diffraction analysis. The mechanism of decomposition under electron impact was determined for (7-methoxy-1,5-dinitro-3-azabicyclo[3.3.1]non-6-en-3-yl)acetic acid.     

The synthesis of 7-hydroxy-3, 9-diazabicyclo[3.3.1]nonane

7-Hydroxy-3, 9-diazabicyclo[3.3.1]nonane is synthesized, starting from the dimethyl ester of the 4-hydroxypiperidine-2, 6-dicarboxylic acid, by preparing the N-benzyl derivative and cyclizing the latter with benzylamine to the benzylimide of the 1-benzyl-4-hydroxypiperidine-2, 6-dicarboxylic acid. On reduction of the given imide with lithium aluminum hydride and catalytic hydrogenolysis of the benzyl groups, the final 7-hydroxy-3,9-diazabicyclo[3.3.1]nonane is obtained, the three-dimensional structure of which (chair-chair type) is proved by comparison of its methyl derivative with a known compound of demonstrated three-dimensional structure.     

9-BBN还原1,7-辛二烯-3-醇的研究

本文报道了用9-BBN与1,7-辛二烯-3-醇进行硼氢化反应的结果。这个反应的区域选择性极低,除生成1-辛烯-3-醇(47％)外,同时还生成了7-辛烯-3-醇(41％)和辛醇-3(12％)。     

Several transformations of 3-benzyl-9-carbethoxymethyl-3,9-diazabicyclo[3.3.1]nonane

The transformations of 3-benzyl-9-carbethoxymethyl-3,9-diazabicyclo[3.3.1]nonane (I) were studied. The dichloride of 9-(-chloroethyl)-3,9-diazabicyclo[3.3.1]nonane, which is readily cyclized in the basic form to 3,9-diazatricyclo[3.3.1.2^3,9]undecane (V), was synthesized by reduction of I with LiAlH₄ and debenzylation with subsequent replacement of the hydroxy group, in the alcohol formed, by chlorine. An unusual cleavage of the carboxymethyl residue to form the nitrogen-unsubstituted dichloride of 3,9-diazabicyclo[3.3.1]nonane (XI) occurs on treatment with thionyl chloride of the acid obtained by saponification and debenzylation of I.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1372–1375, October, 1970.     

Synthesis of novel piperazine based building blocks: 3,7,9-triazabicyclo[3.3.1]nonane, 3,6,8-triazabicyclo[3.2.2]nonane, 3-oxa-7,9-diazabicyclo[3.3.1]nonane and 3-oxa-6,8-diazabicyclo[3.2.2]nonane

The preparation of four novel bridged piperazine building blocks is described: 3,7,9-triazabicyclo[3.3.1]nonane 1, 3-oxa-7,9-diazabicyclo[3.3.1]nonane 2, 3,6,8-triazabicyclo[3.2.2]nonane 3 and 3-oxa-6,8-diazabicyclo[3.2.2]nonane 4. The scaffold of 1 was synthesized from N,N′-dibromobenzenesulfonamide and ethyl acrylate. Compound 2 may be prepared from identical starting materials or alternatively from α,α′-diglycerol. Compounds 3 and 4 were identified as side products from possible aziridinium intermediates.