Project description:The dearomative functionalization of aromatic compounds represents a fascinating but challenging transformation, as it typically needs to overcome a great kinetic barrier. Here, a catalyst-free dearomative rearrangement of o-nitrophenyl alkyne is successfully established by leveraging the remote oxygen transposition and a weak N-O bond acceleration. This reaction features high atom-, step- and redox-economy, which provides a divergent entry to a series of biologically important benzazepines and bridged polycycloalkanones. The reaction is proposed to proceed through a tandem oxygen transfer cyclization/(3 + 2) cycloaddition/(homo-)hetero-Claisen rearrangement reaction. The resulting polycyclic system is richly decorated with transformable functionalities, such as carbonyl, imine and diene, which enables diversity-oriented synthesis of alkaloid-like polycyclic framework.
Project description:Aromatic [5,5]-rearrangement can in principle be an ideal protocol to access dearomative compounds. However, the lack of competent [5,5]-rearrangement impedes the advance of the protocol. In this Article, we showcase the power of [5,5]-rearrangement recently developed in our laboratory for constructing an intriguing dearomative sulfonium specie which features versatile and unique reactivities to perform nucleophilic 1,2- and 1,4-addition and cyclization, thus achieving dearomative di- and trifunctionalization of easily accessible aryl sulfoxides. Impressively, the dearomatization products can be readily converted to sulfur-removed cyclohexenones, naphthalenones, bicyclic cyclohexadienones, and multi-substituted benzenes. Mechanistic studies shed light on the key intermediates and the remarkable chemo-, regio- and stereoselectivities of the reactions.
Project description:Sulfones are fascinating and highly used functional groups, but current syntheses still have limitations. Here, a regiodivergent transition metal-free approach towards sulfones [(E)-allylic sulfones and α-sulfonyl-methyl styrenes] is reported. The method employs commercially available olefins, bases, additives, solvents, and sodium sulfinates (RSO2Na) and produces adducts in good yields. Considering that up to 4 reactions (bromination, dearomative rearrangement, E2, and SN2) are happening, this approach is very efficient. The structures of key adducts were confirmed by X-ray crystallography.
Project description:There is a significant need to develop more rapid and efficient routes to styrene derivatives, since they are extensively used in polymer sciences. This manuscript reports a one-pot synthesis of an array of α-alkyl styrene derivatives from readily available natural products (i.e., estragole and safrole). This method is regioselective, producing a rearranged adduct, under transition metal-free conditions. This methodology has broad nucleophile scope, even tolerating sterically hindered nucleophiles; it is general for carbon, nitrogen, oxygen, and sulfur nucleophiles.
Project description:The Mislow-Braverman-Evans rearrangement, the reversible [2,3]-sigmatropic rearrangement of allylic sulfoxides to allylic sulfenate esters, finds widespread applications in organic synthesis and medicinal chemistry. However, the products of this powerful strategy have primarily been limited to derivatives of allylic alcohols. In contrast, access to structurally similar benzylic alcohols has not yet been established. Described herein is an unprecedented dearomative Mislow-Braverman-Evans rearrangement of aryl sulfoxides to afford benzylic alcohols. A variety of heteroaryl sulfoxides as well as α-naphthyl sulfoxides could be tolerated, and a diverse range of primary, secondary, and tertiary alcohols possessing either alkyl or aryl substituents can be prepared by our protocol with broad functional group tolerance. A patented bioactive molecule could be prepared using our protocol as the key step with exclusive diastereoselectivity, highlighting its potential utility in organic synthesis. Key to the success of the transformation is the dearomative tautomerization to shift the reactive alkene to the exocyclic position enabled by the reversible deprotonation of the benzylic C-H bond, setting the stage for the subsequent [2,3]-sigmatropic rearrangement. Density functional theory (DFT) calculations reveal that protonation of the α-carbon of the sulfoxide is the stereocontrolling step, generating the intermediate that undergoes [2,3]-sigmatropic rearrangement. The full reaction profile is outlined, showing the reversible nature of each step, which causes the observed erosion of the enantiopurity.
Project description:[reaction: see text] A facile route to the alpha-methyl ester of 2-methyleneglutarate via a three-step sequence from 3-hydroxymethylcyclopentene is described. Regioselective formation of the monoacid from a diester precursor proceeds via a novel fluoride-mediated, tandem deprotection/rearrangement of O-silyl 2-(hydroxymethyl)dimethylglutarate.
Project description:An efficient three-step protocol was developed to produce 2-(azidomethyl)oxazoles from vinyl azides in a continuous-flow process. The general synthetic strategy involves a thermolysis of vinyl azides to generate azirines, which react with bromoacetyl bromide to provide 2-(bromomethyl)oxazoles. The latter compounds are versatile building blocks for nucleophilic displacement reactions as demonstrated by their subsequent treatment with NaN3 in aqueous medium to give azido oxazoles in good selectivity. Process integration enabled the synthesis of this useful moiety in short overall residence times (7 to 9 min) and in good overall yields.
Project description:A study on the α-(difluoromethyl)styrene (DFMST) reactivity under conventional radical copolymerization conditions is presented. Although the homopolymerization of DFMST failed, its radical bulk copolymerization with styrene (ST) led to the synthesis of fluorinated aromatic polymers (FAPs). The resulting novel poly(DFMST-co-ST) copolymers were characterized by 1H, 19F and 13C NMR spectroscopies that evidenced the successful incorporation of DFMST units into copolymers and enabled the assessment of their respective molar percentages (10.4-48.2 mol%). The molar masses were in the range of 1900-17 200 g mol-1. The bulkier CF2H group in the α-position induced the lower reactivity of the DFMST comonomer. ST and DFMST monomer reactivity ratios (r DFMST = 0.0 and r ST = 0.70 ± 0.05 at 70 °C) were determined based on linear least-square methods. These values indicate that DFMST monomer is less reactive than ST, retards the polymerization rate, and thus reduces the molar masses. Moreover, the thermal properties (T g, T d) of the resulting copolymers indicate that the presence of DFMST units incorporated into poly(ST) structure promotes an increase of the T g values up to 109 °C and a slightly better thermal stability than that of poly(ST). Additionally, the thermal decomposition of poly(DFMST-co-ST) copolymer (10.4/89.6) was assessed by simultaneous thermal analysis coupled with Fourier-transform infrared spectroscopy and thermogravimetric analysis coupled with mass spectrometry showing that H2O, CO2, CO and styrene were released. The surface analysis was focused on the effects of the -CF2H group at the α-position of styrene comonomers on surface free energy of the copolymer films. Water and diiodomethane contact angle (CA) measurements confirmed that these copolymers (M n = 2300-17 200 g mol-1) are not exactly the same as polystyrenes (M n = 2100-21 600 g mol-1) in the solid state. The CA hysteresis for poly(ST) (6-8°) and poly(DFMST-co-ST) copolymers (3-5°) reflected these differences even more accurately.
Project description:The polycyclic core of the akuammiline alkaloids can be synthesized from simple tryptamine and tryptophol derivatives via a Ag(I)-catalyzed enantioselective dearomative cyclization cascade sequence. The complex tetracyclic scaffolds are prepared via a rapid, versatile, three-step modular synthesis from simple commercially available indole derivatives in high yields and enantiomeric excess (up to 99% yield and >99% ee).
Project description:Polyprenylated acylphloroglucinols (PPAPs) are structurally complex natural products with promising biological activities. Herein, we present a biosynthesis-inspired, diversity-oriented synthesis approach for rapid construction of PPAP analogs via double decarboxylative allylation (DcA) of acylphloroglucinol scaffolds to access allyl-desoxyhumulones followed by dearomative conjunctive allylic alkylation (DCAA).