Direct azidation of unprotected carbohydrates with PPh3/CBr4/NaN3. Modulation of the degree of substitution

We describe herein a modified procedure for the direct and regioselective synthesis of polyazido-sugars, that currently requires multistep syntheses. This protocol allows to modulate the degree of azidation obtained when the reagents to substrate ratio is changed.     

A benzyloxy group migration under Mitsunobu reaction conditions

When compounds 3a and 3b were subjected to a Mitsunobu reaction with benzoylthymine, the expected substitution products were formed together with the regioisomers corresponding to benzyloxy group migrations.     

Direct glycosylation of unprotected and unactivated carbohydrates under mild conditions

Ligand exchange acetalization of acetals in the presence of catalytic amounts of mandelic acid and titanium tert-butoxide is reported. This transformation is successfully extended to glycosylation of unprotected and unactivated pentoses. Even unreactive pentoses such as D-arabinose or D-lyxose can be transformed by this new methodology into corresponding isopropyl glycosides.     

O-Alkylation versus C-alkylation under Mitsunobu conditions

A comparative study of the Mitsunobu reaction at C1 and C6 positions of mannose using bis(2,2,2-trifluoroethyl) malonate as nucleophile is disclosed. While C-alkylation was predominant at the C6 position, only O-alkylation occurred at the anomeric position of the carbohydrate. Some factors playing a role in the selectivity of the reaction are discussed and an inverse mechanism of the Mitsunobu reaction for the anomeric position is proposed.     

O-Alkylation of 3-hydroxyisoxazoles predominates under Mitsunobu conditions

Regiochemical control in the functionalization of ambident nucleophiles is of particular interest in organic chemistry. Herein, we demonstrate that O-alkylation of ambident 3-hydroxyisoxazoles, which are heterocyclic bioisosteres of carboxylic acids, predominates under Mitsunobu conditions. In several cases, excellent O-regioselectivity (?95%) was observed. It is noteworthy that reactions were complete within 15 min at room temperature. Furthermore, the conditions are compatible with a range of alcohols that cover all of the typical protecting groups for the 3-hydroxyisoxazole motif, providing milder, simpler and less hazardous protocols to those commonly followed in the literature.     

Ab initio study of hydrazoic acid

SCF and CI calculations were carried out on the ground^1A state of HN₃. The equilibrium geometry and vibration frequencies were computed. The results point to a planar structure (groupC _s) but to a non-linear (170 °) N-N-N conformation. The calculated vibration frequencies are in fair agreement with experimental assignments.The dissociation path of the molecule to NH and N₂ products was investigated and compared to the isoelectronic reaction of diazomethane. The dissociation energy of hydrazoic acid is estimated to be about –8 kcal/mole, with a potential barrier to dissociation of about 30 kcal/mole.Boursier IRSIA     

Intermolecular cyclocondensation reaction of 3,4-dihydropyrimidine-2-thione under the Mitsunobu reaction conditions

A self-intermolecular cyclocondensation reaction of 3,4-dihydropyrimidine-2-thione(DHPM) to give a novel tricyclic structure containing DHPM core in the presence of diethyl azodicarboxylate(DEAD) and triphenylphosphine(TPP) at room temperature is reported.     

Mitsunobu reactions of nucleoside analogs using triisopropyl phosphite-DIAD

Herein, we report the use of triisopropyl phosphite (TIP) as an effective substitute for triphenylphosphine in the Mitsunobu reaction of nucleoside analogs. In addition, the use of triphenyl phosphite as an alternative reagent for the expensive hexamethylphosphorous triamide (HMPT) in the Véliz-Beal bromination protocol is reported.     

Facile preparation of thiophene C2-ethers using the Mitsunobu reaction

The preparation of thiophene ethers generally requires forcing conditions thus limiting the choice of alkyl substituent. Herein, we report the first successful generally applicable conditions for the selective O-alkylation of 2(5H)-thiophenone.     

Synthesis of soft alkyl phenolic ether prodrugs using Mitsunobu chemistry

The synthesis of soft alkyl phenolic ether prodrugs in excellent yields has been reported by coupling a phenol with a hydroxymethylimide using Mitsunobu chemistry. The imides used in this study include saccharin, phthalimide, succinimide and two other compounds containing acidic imide-like N-H groups, benzotriazole, and imidazole.     

Pummerer rearrangement using bis(p-nitrophenyl) phosphorazidate as an azidation reagent: A novel synthesis of azidomethyl sulfides

A novel method for the synthesis of azidomethyl sulfides by Pummerer rearrangement using bis(p-nitrophenyl) phosphorazidate (p-NO₂DPPA) as an azidation reagent was developed. Various methyl sulfoxides were converted into the corresponding azidomethyl sulfides. Importantly, this reaction enables the preparation of azidomethyl sulfides without the use of toxic or explosive azide sources.     

Reactions of Neomycin B under Mitsunobu Conditions: A Correction of the Literature

Reaction of N‐Boc neomycin with triphenylphosphine and diissopropyl azodicarboxylate in either toluene or THF results in an epoxide in ring IV, not an aziridine or azetidine as previously reported.     

Mitsunobu Reaction: A Powerful Tool for the Synthesis of Natural Products: A Review

The Mitsunobu reaction plays a vital part in organic chemistry due to its wide synthetic applications. It is considered as a significant reaction for the interconversion of one functional group (alcohol) to another (ester) in the presence of oxidizing agents (azodicarboxylates) and reducing agents (phosphines). It is a renowned stereoselective reaction which inverts the stereochemical configuration of end products. One of the most important applications of the Mitsunobu reaction is its role in the synthesis of natural products. This review article will focus on the contribution of the Mitsunobu reaction towards the total synthesis of natural products, highlighting their biological potential during recent years.     

An efficient, one-pot synthesis of trithiocarbonates from the corresponding thiols using the Mitsunobu reagent

A novel Mitsunobu-based protocol has been developed for the synthesis of a variety of symmetrical and unsymmetrical trithiocarbonates from primary, secondary and tertiary thiols using carbon disulfide, in good to excellent yields. This protocol is mild and efficient compared to other reported methods.     

Monoalkylation of dihydroxycoumarins via Mitsunobu dehydroalkylation under high intensity ultrasound. The synthesis of ferujol

Monoalkylation of natural dihydroxycoumarins was carried out by Mitsunobu dehydroalkylation under sonochemical conditions. Aesculetin (6,7-dihydroxycoumarin) was selectively alkylated in good yield with prenyl alcohols at position 7, as clearly shown by NOESY experiments; though less selectively, position 7 was also the most reactive in daphnetin (7,8-dihydroxycoumarin). The synthesis of the phytoestrogen ferujol is also reported for the first time.     

N-3 alkylation of uracils with unprotected amino alcohols using the Mitsunobu reaction

During our search for novel CGRP antagonists, we had great difficulty in accessing one of our key motifs. Herein, we communicate how we solved the problem by an unprecedented Mitsunobu alkylation using unprotected amino alcohols.     

Asymmetric synthesis of (−)-chicanine using a highly regioselective intramolecular Mitsunobu reaction and revision of its absolute configuration

First asymmetric synthesis of (−)-chicanine has been accomplished in 14 steps by employing the Evans asymmetric syn-selective aldol reaction, diastereoselective hydroboration and an regioselective, intramolecular Mitsunobu etherification. The absolute configuration of (+)- and (−)-chicanine has been revised to 2R,3S,4R,5R and 2S,3R,4S,5S, respectively, through CD analysis.     

Synthesis of new hyodeoxycholic acid thiosemicarbazone derivatives under solvent-free conditions using microwave

An efficient and simple method for synthesis of new hyodeoxycholic acid thiosemicarbazone derivatives under solvent-free conditions using microwave has been developed.Its main advantages are short reaction times,good conversions and the environmentally friendly nature of the process.The preliminary results indicate that some of these compounds possess inhibitory effects against E.coli.     

Microwave-assisted expeditious hydrolysis of isobenzofuranone derivatives using silica supported acid under organic solvent-free conditions

Silica sulfuric acid was found to be an efficient, reusable and environment-friendly catalyst for fast hydrolysis of various isobenzofuranone to corresponding 2-ketomethylquinoline derivatives in a high yield under solvent-free using microwave irradiation. As the activator of silica sulfuric acid the wet SiO₂ was chosen. The reactions in conventional conditions were compared with the microwave assisted reactions. This approach can prove beneficial since the recovery of solvents from conventional reaction systems always results in some losses.