Mitsunobu reactions, and

A number of different reaction conditions were investigated for the Mitsunobu reaction and DIAD/PPh3 proved to be the most efficient combination of reagents. The dendronized support was then compared with the conventional TentaCel resin keeping the scaffold on the resin constant (glycine and 4-hydroxyphenylacetic acid) and employing four different alcohols. Much better yields were obtained... 

Sulfahydantoins 87 and 88 are analogues of hydantoins and provide heterocyclic scaffolds with a great potential for the construction of bioactive compounds. A total of 28 derivatives, with crude purity generally higher than 85%, were prepared by parallel synthesis using an oxime resin as a solid support (Scheme 46) . The results constitute the first report of successful Mitsunobu reactions and reductive alkylations on the oxime resin. 

In a follow-up communication,26 similar chemistry was used for the production of 2-substituted benzofurans beginning not with an anthranilic acid derivative, but with a resin-bound ortho-hydroxy aryl iodide 3. In the solid-phase work, depicted in Scheme 5, the relevant carboxylic acid was linked to TentaGel via a Mitsunobu reaction, and after deprotection was seen to undergo smooth Heck coupling and cyclization, giving essentially pure compounds in 40-70% overall yield after cleavage. 

Novel nor-seco baccatin 99 was synthesized in 92% yield through oxidative cleavage of the A ring of 14-OH-DAB (75) with periodic acid via the hydroxy ketone intermediate 100 (Scheme 19). Protection of the 7-hydroxyl of 99 as TES ether followed by reduction of the aldehyde with sodium borohydride yielded nor-seco baccatin alcohol 101 in 80% yield. Nor-seco 13-amino-baccatins 102 and 103 were synthesized from 101 and 99a via the Mitsunobu reaction and reductive amination, respectively, in high yields (Scheme 20). 

The utilization of the Mitsunobu reaction and Dieckmann condensation has been demonstrated for the highly efficient and enantioselective synthesis of loracarbef, starting from the unnatural amino acid (2.V,J .y)-2-amino-3-hydroxy-6-heptenoic acid <2000T5667, 2003TL5991> (Scheme 30). The cyclization step from monocyclic... 

The pyrimidine moiety of 31 was nitrosated and then reduced to give amino derivative 46, which was transformed into 25a as described in Section 14.05.2.6 (Scheme 4). Deprotection of the ribose moiety in acid medium led to 47. The same acidic deprotection conducted on intermediates 31 and 46 led to the pyrimido-l,3-diazocines 48 and 49, respectively (Scheme 8). Starting from xanthosine 42, through isopropylidene protection, the Mitsunobu reaction and deprotection sequence derivative 6 was also synthesized <2004W0013300, 2005TL2825>. 

This type is a one-pot reaction widi all components present fix>m the beginning. The alcohol is first converted into an 5N-activated (HGA) species (43), which undergoes an OX displacement with the carboxylic acid to form the ester (equation 18). Two methods are known to fit into this general scheme the Mitsunobu reaction and die Vorbriiggen-Eschenmoser reaction. ... 

The architecturally novel macrolide (+)-zampanolide was synthesized in the laboratory of A.B. Smith. The C8-C9 ( )-olefin moiety was constructed using the Kocienski-modified Julia oleHnation. The required PT-sulfone was prepared from the corresponding primary alcohol via a two-step protocol employing sequential Mitsunobu reaction and sulfide-sulfone oxidation. The primary alcohol and two equivalents of 1-phenyl-1 H-tetrazolo-5-thiol was dissolved in anhydrous THF at 0 °C and treated sequentially with triphenylphosphine and DEAD. The desired tetrazolo sulfide was isolated in nearly quantitative yield. 

Kodaka, M., Tomohiro, T., Okuno, H. The mechanism of the Mitsunobu reaction and its application to carbon dioxide fixation. J. Chem. 

A novel route for the synthesis of piperazin-2-ones on a solid support relies on an intramolecular Mitsunobu reaction [111]. First, commercially available amino alcohols are attached to an aldehyde resin by reductive ami-nation. The alcohol function is protected and the secondary amine obtained is acylated with an amino add. Sulfonamide activation of the free amino group allows intramolecular alkylation through a Mitsunobu reaction, and thereby the formation of a derivatized ring. 

Winterfeldf s synthesis of brefeldin A (Scheme 1.36) also entailed use of a Michael addition in an anti fashion to a 4-substituted cyclopentenone. Dithiane anion 217 was added in a 1,4 sense to enone 216 to give, after elimination of acetic acid, cyclopentenone 218. Addition of cuprate 219 to 218 in the expected anti manner cleanly afforded the trans cyclopentane 220. Hydride reduction gave the unnatural P-alcohol, which was inverted by a Mitsunobu reaction and the resulting ester cleaved to the desired a-alcohol 221. Protection of the alcohol... 

Walker et al. have described by tliis method a seven-step synthesis of 4-thio-2-deox-y-i3-eri f/7ro-pentosc (37) from 2-dcoxy-D-erir/ira-pentosc via dithioacetals 35 and 36, involving inversion at C-4 by Mitsunobu reaction and final cyclization of the dithioacetal, accompanied by further inversion at C-4. Secrist et al.- have synthesized 39 from the ribose derivative 38 using the same method. Similarly, Imbach et al. have prepared 1,4-dithio-D-ribofuranosides 39 from L-lyxose and from D-ribose,and 1,4-dithio-L-lyxofuranosides 40 from D-ribose. Mackenzie... 

The, 2 -seco-AZT 55 and its 3 R,4 S diastereomer 57 were prepared from coupling of thymine with 54 and 56, respectively, followed by deprotection, tritylation, azido formation via a Mitsunobu reaction, and detrityl-ation. The chiral acyclic side chains were derived from D-isoascorbic acid (92MI1). 

Zinc azide bis-pyridine complex (the more stable form of zinc azide) behaves as an excellent nucleophile in the Mitsunobu reaction and furnishes (R)-azidoester 96 in high yield with complete inversion at C-2 [38]. 

Mitsunobu reaction this was later applied widely in sugar chemistry by his collaborators Janusz Jurczak, Grzegorz Grynkiewicz, and Edward Grochowski. They discovered valuable new applications of the Mitsunobu reaction and explained mechanistic aspects. 

The oxorhenium(V) complex 80 has been prepared from 2, 3 -diamino-2, 3 -dideoxyadenosine, and exists as a 2 1 mixture of syn- and an/i-isomers. Both were inhibitors of purine-specific ribonuclease, with the 57/i-isomer being more effective. " The same group has described a route to 3, 5 -diamino-3, 5 -dideoxy-adenosine (82) from the /> xo-epoxide 81 (Vol. 25, p. 251-2), as outlined in Scheme 10. The Mitsunobu inversion using benzyl alcohol as nucleophile is noteworthy, and proved superior to other strategies. An oxorhenium(V) complex was also formed from 82." Thymidine can be converted into the anhydronucleo-side 83 by two successive Mitsunobu reactions, and 83 was converted into the aminoderivative 84 of AZT, and some phosphoramidates were produced from 84." Some 5 -deoxy-5 -sulfonylamido derivatives of AZT have also been produced by successive displacements at 0-5 and 0-3 by nitrogen nucleophiles." ... 

This reaction was initially reported by Fukuyama and co-workers in 1995. It is a two-step conversion of primary amines into secondary amines via ortho-nitrobenzenesulfonation in conjunction with the Mitsunobu Reaction and subsequent removal of the o-nitrobenzenesulfonyl group by thiophenol. Therefore, this reaction is generally known as the Fukuyama amine synthesis. In addition, it is also referred to as the Fukuyama-Mitsunobu A -alkylation," Fukuyama-Mitsunobu alkylation, Fukuyama-Mitsunobu condition, Fukuyama-Mitsunobu procedure, or Fukuyama-Mitsunobu Reaction. In this reaction, the o-nitrobenzenesulfonyl-protected amine is alkylated with alcohol in the presence of PPhs and diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD), and the deprotection occurs in a very mild condition (almost neutral ). The o-nitrobenzenesulfonyl group is simply called the Fukuyama sulfonamide protecting groupThis reaction has become a versatile method... 

The total synthesis of ditryptophenaline (651) used stereoisomer 637, which was oxidized (—> 645) and reduced to give diol 646 (Scheme 10.5). Analogous to the previously described synthesis, 646 was subjected to a Mitsunobu reaction and reduction to furnish cyclization product 647. Benzyl deprotection and coupling with a Fmoc-protected W-methyl-(5)-phenylalanine derivative yielded tetrapeptide 648. TMSE-deprotection, two oxidations (—> 650), Fmoc-deprotection, and DCC-mediated cyclization finally led to the natural product ditryptophenaline (651). 

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