Diastereoselective functionalisation of benzo-annulated bicyclic sultams: Application for the synthesis of cis-2,4-diarylpyrrolidines

• Susan Kelleher,
• Pierre-Yves Quesne and
• Paul Evans

Beilstein J. Org. Chem. 2009, 5, No. 69, doi:10.3762/bjoc.5.69

• vinyl bromide 24a in lithiation and Pd-coupling chemistry is described. In the case of the latter, hydrogenation of the styryl products afforded a single diastereoisomer. These compounds were then studied under dissolved metal reduction conditions, in which the cleavage of both N–S and C–S bonds takes

• vinyl bromides 24a and 24b in good yields, respectively (Scheme 7). Vinyl bromide 24a was then subjected to lithiation with t-BuLi, followed by a CO2 quench. The desired carboxylic acid recovered from this reaction was only formed in low yields possibly due to issues with competing directed ortho

• -lithiation [25]. Notwithstanding, this acid was transformed into the corresponding methyl ester 25 using a Steglich-type esterification. Alkenyl reduction of the α,β-unsaturated ester under standard conditions gave the product of hydrogenation as an undetermined 3:1 mixture of diastereoisomers. The likely

Synthesis of unsymmetrically substituted biaryls via sequential lithiation of dibromobiaryls using integrated microflow systems

• Aiichiro Nagaki,
• Naofumi Takabayashi,
• Yutaka Tomida and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2009, 5, No. 16, doi:10.3762/bjoc.5.16

• micromixers and four microtube reactors to obtain unsymmetrically substituted biaryl compounds. Keywords: dibromobiaryls; fast mixing; integrated microflow system; selective lithiation; unsymmetrically substituted biaryls; Introduction Unsymmetrical biaryls have received significant research interest

• lithiation of dibromobiaryls using an integrated microflow system. These observations may open a new aspect of the synthesis of unsymmetrically substituted biaryls (Scheme 1), and herein we report full details of this study. Results and Discussion Br-Li Exchange Reaction of 2,2′-Dibromobiphenyl First, we

Convenient methods for preparing π-conjugated linkers as building blocks for modular chemistry

• Jiří Kulhánek,
• Filip Bureš and
• Miroslav Ludwig

Beilstein J. Org. Chem. 2009, 5, No. 11, doi:10.3762/bjoc.5.11

• ′-bromobiphenyl intermediates necessary for the preparation of 4a–c were synthesized by the Suzuki–Miyaura cross-coupling of 1-bromo-4-iodobenzene with the corresponding boronic acids/esters 1a–c in the yields of 82, 84, and 91%, respectively. A routine procedure involving a lithiation and reaction with

• % yield). Since the Sonogashira reaction between bromo derivatives and trimethylsilylacetylene proved to be sluggish and low yielding (even with a large excess of acetylene and elevated temperature), the bromo derivatives were converted to the corresponding iodo derivatives by lithiation and quenched with

• . Overall 12 extended π-linkers have been easily synthesized (8 of them are new compounds) utilizing procedures such as a lithiation/reaction with triisopropyl borate/esterification with pinacol, Mizoroki–Heck coupling with vinylboronate pinacol ester, borylation with bis(pinacolato)diboron or Sonogashira

Enantiospecific synthesis of [2.2]paracyclophane- 4-thiol and derivatives

• Gareth J. Rowlands and
• Richard J. Seacome

Beilstein J. Org. Chem. 2009, 5, No. 9, doi:10.3762/bjoc.5.9

• by sulfinyl-directed ortho lithiation with n-butyllithium followed by reaction with tosyl azide. The resulting azo[2.2]paracyclophane was reduced in situ to give the amine (Rp,RS)-8 in good yield for the two steps (Scheme 2). Trichlorosilane-mediated deoxygenation proceeded uneventfully to furnished

Trifluoromethyl ethers – synthesis and properties of an unusual substituent

• Frédéric R. Leroux,
• Baptiste Manteau,
• Jean-Pierre Vors and
• Sergiy Pazenok

Beilstein J. Org. Chem. 2008, 4, No. 13, doi:10.3762/bjoc.4.13

• potassium tert-butoxide (KOR) in tetrahydrofuran at −100 °C. Upon trapping with molecular iodine, 3-iodo-4-trifluoromethoxybiphenyl was isolated in 90% yield [73]. Under the same conditions as employed with trifluoromethoxybenzene, 1- and 2-trifluoromethoxynaphthalene undergo selective lithiation at the 2

• lithiation next to the OCF3 substituent is favoured, probably due to steric reasons. In fact, 1-trifluoromethoxy-4-(trifluoromethyl)benzene (Scheme 15) affords 2-trifluoromethoxy-5-(trifluoromethyl)benzoic acid after lithiation and carboxylation [75]. When the OCF3 substituent is in competition with fluorine

Development of potential manufacturing routes for substituted thiophenes – Preparation of halogenated 2-thiophenecarboxylic acid derivatives as building blocks for a new family of 2,6-dihaloaryl 1,2,4-triazole insecticides

• John W. Hull Jr.,
• Duane R. Romer,
• David E. Podhorez,
• Mezzie L. Ash and
• Christine H. Brady

Beilstein J. Org. Chem. 2007, 3, No. 23, doi:10.1186/1860-5397-3-23

• -thiophenecarbonyl chloride 2 was developed from tetrachlorothiophene via either a lithiation reaction with n-butyllithium in MTBE solvent, or by a previously reported Grignard method using 1,2-dibromoethane as activator, followed by carbonation of the anion with CO2 to give the trichloro-2-thiophenecarboxylic acid

• with CO2, 3,4,5-trichloro-2-thiophenecarboxylic acid 23 was isolated and dried prior to its conversion to 2 with thionyl chloride. Thus, 2 can be prepared in two chemical steps from the inexpensive chlorinated thiophene 22 using either lithiation or Grignard chemistry. [28] A comparison of some key

• manufacturing issues surrounding the two proposed routes to 2 via 23 is summarized in Table 2. The two routes are dramatically different and lead to significantly different yields. At first glance, the lithiation route is clearly superior due to the 92% isolated yield, and the formation of only one equivalent