Preparation of polyfunctional arylmagnesium reagents bearing a triazene moiety. A new carbazole synthesis

[reaction: see text] The reaction of iodo- or bromo-substituted aryltriazenes with i-PrMgCl.LiCl generates the corresponding magnesiated derivatives which react with various electrophiles (acid chlorides, 3-iodoenones, allylic halides, aldehydes) affording polyfunctional triazenes. They can be readily converted to the corresponding polyfunctional aryl iodides. This new synthetic strategy was applied to prepare functionalized carbazoles.     

Trans-hydrometalation of alkynes by a combination of InCl3 and DIBAL-H: one-pot access to functionalized (Z)-alkenes

[reaction: see text] Triethylborane-induced hydrometalation of alkynes proceeds in an anti manner to afford the corresponding (Z)-alkenylmetal compounds stereoselectively, where dichloroindium hydride would play a key role. A variety of functional groups including hydroxy, carbonyl, and carboxy groups were tolerant under the reaction conditions. Following iodolysis and cross-coupling reaction of the (Z)-alkenylmetal species show the usefulness of this strategy.     

Synthesis of 2-mercaptobenzothiazoles via DBU-promoted tandem reaction of o-haloanilines and carbon disulfide

An efficient strategy for the synthesis of a variety of 2-mercaptobenzothiazole derivatives has been developed. The reaction proceeded from o-haloaniline derivatives and carbon disulfide via a tandem reaction in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to afford the corresponding 2-mercaptobenzothiazole derivatives in good to excellent yields.     

A protocol to 2-aminobenzimidazoles via copper-catalyzed cascade addition and cyclization of o-haloanilines and carbodiimides

An efficient strategy for the synthesis of a variety of 2-animobenzimidazole derivatives has been developed. The reaction proceeded from o-haloanilines and carbodiimides via copper(I)-catalyzed domino reaction in the presence of tert-butoxide to afford the corresponding 2-animobenzimidazole derivatives in good to excellent yields. o-Haloanilines could be o-iodoaniline, o-bromoaniline, and o-chloroaniline derivatives. Carbodiimides could be symmetrical and unsymmetrical substrates with aryl or alkyl substituents. The reaction exhibited a good regioselectivity when unsymmetrical carbodiimides were employed.     

An efficient synthesis of cyanamide from amine promoted by a hypervalent iodine(III) reagent

In a one-pot strategy we have achieved an efficient method for the synthesis of organic cyanamides starting from dithiocarbamic acid salts/amines. In this strategy the in situ generated alkyl or aryl isothiocyanates, obtained by the desulfurization of dithiocarbamic acid salts with diacetoxyiodobenzene (DIB) react with aqueous ammonia forming alkyl or aryl thiourea which on subsequent oxidative desulfurization with DIB led to the formation of corresponding cyanamide in good yields. Mild reaction conditions, shorter reaction time, an environmentally benign protocol, and easy isolation of the desired product make the present methodology a suitable alternative for the preparation of various organic cyanamides.     

Convenient asymmetric synthesis of beta-trifluoromethyl-beta-amino acid, beta-amino ketones, and gamma-amino alcohols via Reformatsky and Mannich-type reactions from 2-trifluoromethyl-1,3-oxazolidines

The stereoselective syntheses of beta-trifluoromethyl-beta-amino ester, beta lactams, and beta-amino ketones starting from an oxazolidine derived from trifluoroacetaldehyde hemiacetal and (R)-phenylglycinol are reported. The Mannich-type reaction involving a chiral fluorinated iminium ion occurred in a good yield and with a higher stereoselectivity (dr up to 96:4) than that of the Reformatsky-type reaction. This straightforward strategy was applied to the short syntheses of (R)-3-amino-4,4,4-trifluorobutanoic acid, a series of novel enantiopure unprotected fluorinated beta-amino ketones, and their corresponding gamma-amino alcohols.     

Stereoselective synthesis of 2-dienyl-substituted piperidines using an eta4-dienetricarbonyliron complex as the stereocontrolling element in a double reductive amination cascade

In the presence of NaBH(OAc)(3), a 1,5-keto-aldehyde, contained within a side-chain of an eta(4)-dienetricarbonyliron complex, undergoes a double reductive amination sequence with a series of primary amines, to provide the corresponding piperidine products in good to excellent yield. The dienetricarbonyliron complex functions as a powerful chiral auxiliary in this cascade process, exerting complete control over the stereoselectivity of the reaction, with the formation of a single diastereoisomeric product. The sense of stereoinduction has been confirmed by X-ray crystallography. Removal of the tricarbonyliron moiety can be effected with CuCl(2) to afford the corresponding 2-dienyl-substituted piperidine in excellent yield. Attempted extension of this cyclisation strategy to the corresponding azepane ring system using a 1,6-keto-aldehyde as the cyclisation precursor was unsuccessful; in this case, the reaction stopped after a single reductive amination on the aldehyde to provide an acyclic keto-amine product.     

Assembly of 3-substituted isocoumarins via a CuI-catalyzed domino coupling/addition/deacylation process

An efficient strategy for the synthesis of a variety of 3-substituted isocoumarins has been developed. The reaction proceeded from o-halobenzoic acids and 1,3-diketones via a copper(I)-catalyzed domino reaction in DMF under the action of K(3)PO(4) at 90-120 °C without a ligand to afford the corresponding 3-substituted isocoumarin derivatives in good to excellent yields. o-Halobenzoic acids could be o-iodobenzoic acid, o-bromobenzoic acid, and o-chlorobenzoic acid derivatives. 1,3-Diketones could be alkyl- and aryl-substituted 1,3-diketones.     

Synthesis of polyketides via diastereoselective acetalization

[reaction: see text] Diastereoselective acetalization of pseudo-C(2)-symmetric 1,3,5-triol systems is a general strategy for the rapid generation of polyketides. The oxidative acetalization reaction shown above was studied under both kinetic and thermodynamic conditions, using synthetic 1,3,5-triol units. In addition, all possible stereochemical variants of a 1,3,5-triol system were prepared from the corresponding acetal to expand the synthetic versatility of this method.     

Catalytic Enantioselective Quick Route to Aldol‐Tethered 1,6‐ and 1,7‐Enynes from ω‐Unsaturated Aldehydes

An effective asymmetric route to functionalized 1,6‐ and 1,7‐enynes has been developed based on a direct cross‐aldol reaction between ω‐unsaturated aldehydes and propargylic aldehydes (α,β‐ynals) promoted by combined α,α‐dialkylprolinol ether/Brønsted acid catalysis. This synergistic activation strategy is key to accessing the corresponding aldol adducts with high stereoselectivity, both enantio‐ and diastereoselectivity. The aldol reaction also proceeds well with propargylic ketones (α,β‐ynones) thus enabling a stereocontrolled access to the corresponding tertiary alcohols. The utility of these adducts, which are difficult to prepare through standard methodology, is demonstrated by their transformation into trisubstituted bicyclic enones using standard Pauson–Khand conditions.     

Total synthesis of ciguatoxin and 51-hydroxyCTX3C

Ciguatoxins, the principal causative toxins of ciguatera seafood poisoning, are large ladder-like polycyclic ethers with the 13 ether rings ranging from five- to nine-membered. In this paper, we describe the total synthesis of the two most toxic members of the ciguatoxin family, ciguatoxin 1 and 51-hydroxyCTX3C 2, based on a unified synthetic strategy. The key features in our syntheses were (i) direct construction of the O,S-acetal from the corresponding left and right wing fragments (3, 4, 14); (ii) stereo- and chemoselective radical reaction of the alpha-oxyradical with pentafluorophenyl acrylate to achieve cyclization of the seven-membered G-ring; (iii) ring-closing metathesis reaction to build the nine-membered F-ring; and (iv) an efficient protective group strategy using the oxidatively removable 2-naphthylmethyl groups.     

Rearrangement of epoxynitriles: a convenient homologation of acyclic and cyclic ketones to carboxylic acids

A convenient two-step homologation of both aliphatic and aromatic ketones to the corresponding carboxylic acid has been developed. First ketones were converted to epoxynitriles with the Darzens reaction. Second, a Lewis acid mediated rearrangement of these epoxynitriles with lithium bromide was achieved to give homologated secondary alkanoic acids (as well as aryl-alkanoic) in good yields. The mechanism and the scope of the rearrangement reaction were investigated. This strategy constitutes a two-step homologation of ketones to secondary carboxylic acids.     

'Double asymmetric induction' as a novel tool for high stereocontrol in Baylis-Hillman reaction

The strategy of double asymmetric induction was utilized in Baylis-Hillman reaction for the first time by the coupling of chiral aldehydes with chiral acrylate (1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose-3-acrylate) to obtain corresponding adducts with high syn diastereoselectivities (de >90%) in moderate to good yields.     

An Efficient Method for Sulfonylation of Amines,Alcohols and Phenols with N-Fluorobenzenesulfonimide Under Mild Conditions

A new and convenient procedure was developed for the preparation of sulfonamides and sulfonic esters using N-fluorobenzenesulfonimide(NFSI) as a novel phenylsulfonyl group transfer reagent. In this protocol, a broad range of functional groups were tolerated to give the corresponding sulfonamides or sulfonic esters in moderate to excellent yields. The synthetic strategy for sulfonamides formation proceeded efficiently even under base-, metal-and additive-free conditions with the advantages of operational simplicity, mild reaction conditions as well as short reaction time.     

Mimicking dihydroxy acetone phosphate-utilizing aldolases through organocatalysis: a facile route to carbohydrates and aminosugars

[reaction: see text] A practical and environmentally friendly organocatalytic strategy designed to mimic the DHAP aldolases has been developed and shown to be effective in the preparation of carbohydrates and aminosugars. (S)-Proline and (S)-2-pyrrolidine-tetrazole catalyzed the aldol reaction between dihydroxy acetone variants such as 1,3-dioxan-5-one and 2,2-dimethyl-1,3-dioxan-5-one with aldehydes to give the corresponding polyols in good yields with very high ees.     

Enantioselective 1,3-dipolar cycloadditions of diazoacetates with electron-deficient olefins

[reaction: see text] A general strategy for highly enantioselective 1,3-dipolar cycloaddition of diazoesters to beta-substituted, alpha-substituted, and alpha,beta-disubstituted alpha,beta-unsaturated pyrazolidinone imides is described. Cycloadditions utilizing less reactive alpha,beta-disubstituted dipolarophiles require elevated reaction temperatures, but still provide the corresponding pyrazolines with excellent enantioselectivities. Finally, an efficient synthesis of (-)-manzacidin A employing this cycloaddition methodology as a key step is illustrated.     

Lewis Acid Catalyzed Asymmetric Three‐Component Coupling Reaction: Facile Synthesis of α‐Fluoromethylated Tertiary Alcohols

A chiral dicationic palladium complex is found to be an efficient Lewis acid catalyst for the synthesis of α‐fluoromethyl‐substituted tertiary alcohols using a three‐component coupling reaction. The reaction transforms three simple and readily available components (terminal alkyne, arene, and fluoromethylpyruvate) to valuable chiral organofluorine compounds. This strategy is completely atom‐economical and results in perfect regioselectivities and high enantioselectivities of the corresponding tertiary allylic alcohols in good to excellent yields.     

Silver-catalyzed decarboxylative C–H functionalization of cyclic aldimines with aliphatic carboxylic acids

Silver-catalyzed decarboxylative C–H alkylation of cyclic aldimines with abundant aliphatic carboxylic acids has been realized under mild reaction conditions generating the corresponding products in moderate to good yields (32%–91%). In addition, a gram-scale reaction, late-stage modification of drug, synthetic transformation of the product, and further application of the catalytic strategy were also performed. Preliminary studies indicate that the reaction undergoes a radical process.     

Use of F-BODIPYs as a protection strategy for dipyrrins: optimization of BF(2) removal

We recently reported the first general method for the deprotection of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (F-BODIPYs) involving a microwave-assisted procedure for the removal of the BF(2) moiety, and liberation of the corresponding free-base dipyrrin. Further optimization of the reaction has resulted in a more convenient and accessible protocol. The availability of this new methodology enables BF(2)-complexation to be used as a dipyrrin protection strategy. Herein lies a detailed examination of the deprotection reaction, with a view to optimization and gaining mechanistic insight, and its application in facilitating a multistep synthesis of pyrrolyldipyrrins.     

An efficient synthesis of beta-C-glycosides based on the conformational restriction strategy: Lewis acid promoted silane reduction of the anomeric position with complete stereoselectivity

[reaction: see text] The reduction of glyconolactols having an anomeric carbon substituent by Et(3)SiH/TMSOTf proceeded with complete stereoselectivity to produce the corresponding beta-C-glycosides when the substrates were conformationally restricted in the (4)C(1)-chair form by a 3,4-O-cyclic diketal or a 4,6-O-benzylidene protecting group. Thus, the efficient construction of beta-C-glycosides was achieved on the basis of the conformation restriction strategy.