Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• ’-difluorobipyridinium salts and N,N’-difluoro-1,4-diazoniabicyclo[2.2.2]octane salts, and their many derivatives and analogs, including chiral N-F reagents such as optically active N-fluoro-sultam derivatives, N-fluoro-alkaloid derivatives, DABCO-based N-F derivatives, and N-F binaphthyldisulfonimides. The synthesis

• ketones, as is illustrated with representative in Scheme 65. In addition, the Takeuchi group reported a spiro-type analogue, (2'S,3R,5'R)-2-fluoro-2'-methylethyl-5'-methyl-2H,4H-spiro[benzo[e][1,2]thiazine-3,1'-cyclohexane]-1,1-dione (28-7a) [94], as their third chiral reagent in this sultam series. As

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• )amine (TTTA) as ligand, and THF as solvent at 50 °C. The obtained sulfonamide-tethered 5-iodo-1,2,3-triazoles 103 were then cyclized upon heating in the presence of Cs2CO3 to give triazole-fused sultams 104. A good to excellent yield of sultam derivatives 104 containing aryl and alkyl substituents on

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• results with α-bromocarboxylic acid derivatives 167 substituted with Oppolzer’s camphor sultam, which provided carboxylated products 168 in good yield (80%) and excellent diastereomeric ratio (98:2) (Scheme 53). The same group reported an electrocatalytic Michael addition of chiral acetoacetic derivatives

• acetoacetates of Oppolzer’s sultam and Evans’ oxazolidin-2-ones afforded the best yields and diastereomeric ratios of addition products 170 relative to what was achieved with other chiral auxiliaries [98]. As a part of studies on the effects of chiral auxiliaries on the stereoselectivity in electrochemical

• resulted in the corresponding 2-phenylsuccinate esters 172 and 172' in satisfactory yields. The best diastereoselectivities were obtained using Oppolzer’s camphor sultam (172f + 172f') and 4R-(diphenylmethyl)oxazolidin-2-one (172c + 172'c) as chiral auxiliaries (Scheme 55). Martens and his group

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• diastereoselectivities of 1,3-dipolar cycloadditions which allow to control stereochemistries at C3 and C5 [79][80]. To illustrate this concept the E/Z mixture of nitrone 70 was reacted with acrylamide 71 prepared from (2S)-bornane-10,2-sultam to afford mainly (20:1) the isoxazolidine (3S,5S)-72 easily separable from

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• by Fujii, Otaka and co-workers, which showed that the sultam moiety is a useful chiral auxiliary to control the stereochemistry during the incorporation of the lateral chain (see Scheme 15) [37]. The copper-mediated reduction of 3,3-difluoropropene 40 bearing a sultam (Xs) as a chiral auxiliary

• ) afforded the final dipeptide isosteres 79a and 79b. The sultam Xs moiety has also been used as chiral auxiliary for the synthesis of Xaa-[CF=CH]-Xaa [37]. Otaka and co-workers developed a one-pot methodology to access amide isosteres at the C-terminal (Scheme 15) [47]. Cyanide-mediated reductive

• . Interestingly, different amino acids, such as H2N-Gly-OEt, H2N-Val-OMe and H2N-Pro-OMe, could be used instead of the sultam 81 to access tripeptide isosteres in a racemic manner (not shown). Fujii and co-workers also used the sultam Xs as a chiral auxiliary but started their synthesis with 3,3-difluoropropenes

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• , the tertiary analogue 5 underwent cyclization smoothly and rapidly (1 h) under the same conditions to furnish the benzannelated sultam 6 in 78% yield (Scheme 2). Thus, in order to enable the preparation of arene-annelated tertiary sultams of type 6 along this route, an effective and versatile access

• equivalents of NaH. Although full conversion of 8a was achieved and the NMR-determined yield of sultam 10a was 89% (Table 1, entry 1), attempts were made to further improve the reaction conditions by testing different bases such as potassium tert-butoxide and sodium methoxide in dioxane and potassium

• carbonate in dioxane as well as in DMAA (Table 1, entries 2–5). Unfortunately, in all cases the yields of the target sultam 10a were poorer. Since NaH in dioxane had given the best results, various parameters of these conditions were tested. With a reduced amount of NaH (2.5 instead of 4.0 equiv) the

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• group and the sulfonylimine. One way to achieve this could be in the chemoselective reduction of the C=N group of oxoimide 3, addition of the alkynyl moiety to the carbonyl group, and re-oxidation of the sultam to the sulfonimide (see Scheme 4). There are a number of reductions of oxoimide 3 reported in

• (OiPr)3/iPrOH), a mixture of the 3-hydroxyimine, 3-oxocamphorsultam and 3-exo-hydroxycamphorsultam is produced. Prolonged reaction over several weeks eventually leads to 3-exo-hydroxycamphorsultam as the sole product. We now found that the sulfonylimine of 3 could be reduced selectively to the sultam 14

• in the presence of Zn/HOAc, as shown in Scheme 4. The product shows an IR stretching vibration at 1760 cm−1 and a 13C NMR signal at 209.7 ppm for the unreacted C=O group. The presence of the sultam can be deduced from the NH stretching vibration at 3180 cm−1, a 13C signal of the sulfonamide carbon at

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• of 3.3:1 with its diastereomer, not shown) in 45–50% overall yield. The camphor-derived nitroso agents 140a–d have also been used with great success in hetero-Diels–Alder reactions (Table 5). The sultam 140a gave the products with high stereoselectivity when reacted with both cyclopentadiene and

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• skeletally diverse bi-, and tricyclic sultam derivatives (sulfonamide analogs) using norbornenyl sultam 272 as a core unit assembled by an intramolecular Diels–Alder (IMDA) reaction via a domino ROM–RCM–CM cascade. Diversity has been incorporated by using various cross-metathesis partners (Scheme 56). Basso

• pyran derivatives. RRM of various functionalized oxanorbornene systems. RRM to assemble the spiro fused-furanone core unit. (i) 129, benzene, 55 °C, 3 days; (ii) Ph3P=CH2Br, n-BuLi, THF, 0 °C; (iii) 129, benzene, 40 °C, 24 h; (iv) catalyst 2 (10 mol %), CH2Cl2, 35 °C. RRM protocol to norbornenyl sultam

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• starting N-enoyl sultam and the product from the DCA reaction can be purified by recrystallization, and the auxiliary is easily removed. Another sultam-based chiral auxiliary that has been used is bicycle 5 [38]. The authors were able to demonstrate that use of auxiliary 5 in the DCA reaction of 11

• provided an increase in diastereoselectivity and a higher yield of the product after deprotection of the sultam group over the Oppolzer auxiliary (Scheme 3). The Evans auxiliary 6 has been used extensively in several asymmetric transformations such alkylations, allylations and most notably for aldol

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• reported the synthesis of highly functionalized pyrrolidines 77 in a MCR involving classical aliphatic aldehydes 74, chiral glycyl sultam 75 and activated alkenes 76 (Scheme 37) [96]. The Oppolzer’s camphorsultam, incorporated in the amine 75 by means of an amide linkage, plays two different roles. On the

Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach

• Andivelu Ilangovan and
• Shanmugasundar Saravanakumar

Beilstein J. Org. Chem. 2014, 10, 127–133, doi:10.3762/bjoc.10.9

• , (+)-grandiamide D, dasyclamide and gigantamide A, isolated from leaves of Aglaia gigantea, by making use of a common synthetic intermediate prepared by the Baylis–Hillman reaction. Asymmetric synthesis of the natural (+)-grandiamide D was accomplished from camphor sultam. Keywords: Baylis–Hillman reaction

• (+)-grandiamide D (5). We assumed that the asymmetric Baylis–Hillman reaction [15] would be an ideal way to introduce chirality. Reaction between acryloyl sultam 19, and 2-((4-methoxybenzyl)oxy)acetaldehyde (14) in DMF [12], afforded cyclic product 20, which was then treated as such with TEA in ethanol to afford

Facile synthesis of benzothiadiazine 1,1-dioxides, a precursor of RSV inhibitors, by tandem amidation/intramolecular aza-Wittig reaction

• Krishna C. Majumdar and
• Sintu Ganai

Beilstein J. Org. Chem. 2013, 9, 503–509, doi:10.3762/bjoc.9.54

• yields and high purity, which is the core moiety of RSV inhibitors. Keywords: benzothiadiazine-3-one 1,1-dioxide; 3-ethoxy-1,2,4-benzothiadiazine 1,1-dioxide; intramolecular aza-Wittig reaction; sultam; Introduction Sultams have gained popularity in the scientific community especially among synthetic

• -dioxide 7, which can easily be obtained by simple hydrolysis of the benzothiadiazine 1,1-dioxide derivative 8. Construction of this six-membered sultam 8 was thought to be achieved by intramolecular aza-Wittig reaction of the o-azido derivative 9. The following retrosynthetic analysis led us to the

Exploring chemical diversity via a modular reaction pairing strategy

• Joanna K. Loh,
• Sun Young Yoon,
• Thiwanka B. Samarakoon,
• Alan Rolfe,
• Patrick Porubsky,
• Benjamin Neuenswander,
• Gerald H. Lushington and
• Paul R. Hanson

Beilstein J. Org. Chem. 2012, 8, 1293–1302, doi:10.3762/bjoc.8.147

• nucleophilic aromatic substitution (SNAr) diversification pathway is reported. Eight benzofused sultam cores were generated by means of a sulfonylation/SNAr/Mitsunobu reaction pairing protocol, and subsequently diversified by intermolecular SNAr with ten chiral, non-racemic amine/amino alcohol building blocks

• literature for the synthesis of 5-, 6- and 7-membered benzofused sultams, reports on the generation of 8-membered benzofused sultams have been sparse [20][21][22]. In this regard, our group has focused on the development of several methodologies and protocols for the generation of diverse sultam collections

• on multigram scale through the use of three efficient steps, namely sulfonylation, Mitsunobu alkylation and SNAr, to generate both stereoisomers of each core [37] (Scheme 2). The bridged benzofused sultam scaffolds were prepared by a sulfonylation intramolecular SNAr protocol, reported previously [32

Development of the titanium–TADDOLate-catalyzed asymmetric fluorination of β-ketoesters

• Lukas Hintermann,
• Mauro Perseghini and
• Antonio Togni

Beilstein J. Org. Chem. 2011, 7, 1421–1435, doi:10.3762/bjoc.7.166

• experiment. Structure of the chiral ansa-metallocene [(EBTHI)Ti(OTf)2]. Electrophilic fluorinating reagents of the N–F-type. F–TEDA [27]; NFTh = 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) [84]; NFSI = N-fluorobenzosulfonimide [85]; SaSu–NF = saccharine-sultam derived NF

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• , and catalytic Pd2(dba)3·CHCl3 led to the production of the desired sultams 42 upon heating at 110 °C. A series of sultam derivatives of bioactive, related isoindol-1-one amides 43 were also prepared by entering acrylic acid into the Heck–aza–Michael process and coupling a second amine derivative

• . Synthesis of pyrroles by cyclization of propargyl amines. Isoindolone and phthalazone synthesis by cyclization of acylhydrazides. Sultam synthesis by cyclization of sulfonamides. Synthesis of sulfonamides by aminosulfonylation of aryl iodides. Pyrrolidine synthesis by carbopalladation of allylamines

Synthesis of 5-(6-hydroxy-7H-purine-8-ylthio)- 2-(N-hydroxyformamido)pentanoic acid

• Yanmei Zhang,
• Greg Elliot,
• Adrian Saldanha,
• Igor Tsigelny,
• Dennis Carson and
• Wolf Wrasidlo

Beilstein J. Org. Chem. 2010, 6, 742–747, doi:10.3762/bjoc.6.93

• −78 °C. n-Butyllithium (2.5 M in hexane, 1.95 mL, 4.87 mmol) was added dropwise to a solution of sultam 2’ (1.0 g, 4.64 mmol) in dry THF (20.0 mL) at −78 °C. The solution was stirred at −78 °C for 10 min, and then transferred, via a cannula, to the solution of the mixed anhydride prepared above. The

• sultam, then acidified with 2 N HCl (until pH 2). The cloudy aqueous solution was then extracted with ethyl acetate (3 × 25 mL). The combined ethyl acetate solution was dried with sodium sulfate and concentrated. The residue was purified by column chromatography with DCM–MeOH–AcOH (120:20:1) as eluent to