Mannich borono

Petasis (borono-Mannich) condensation (Scheme 91) [353] To piperazinetrityl resin (32 mg, 0.030 mmol, loading 0.95 mmol g ) weighed out in a 10-mL Teflon fritted vessel was added a solution of glyoxylic acid monohydrate (0.032 mmol) in dry THE (2 mE). The suspension was allowed to mix under N2 at r. t. for 2 h. An excess of DEAM-PS boronic ester (120 mmol) was then added, followed by THP/EtOH 8 3 (v/v) (1.5 mE). The suspension was mixed under N2 at 55 °C for 48 h and then cooled at r.t. The resin mixture was filtered and washed as follows ... 

Candeias NR, Montalbano F, Cal PMSD et al (2010) Boronic Acids and Esters in the Petasis-Borono Mannich Multicomponent Reaction. Chem Rev 110 6169-6193... 

A series of functionalized 2,5-dihydrofurans was efficiently synthesized via an amine-promoted Petasis borono-Mannich reaction and a... 

The preparation of such dihydropyrans derivatives 21-23 modified at the C-6 position by a hydrophobic substituent (zsopentyl side chain) analogous to the oseltamivir side chain is summarized in Scheme 7. It uses the borono-Mannich Petasis reaction between an amine, ot-hydro)yaldehyde 25 and boronic acid 26. This reaction proceeds with remarkably high stereocontrol, producing 1,2-aminoalcohols with an a tf-configuration. The resulting acyclic aminoalcohol 24 is the key precursor to the functionalized cyclic dihydropyrans 21-23 with the proper functionality and stereochemistry at C4. 

Organoboron compounds have gained special attention and importance in the last years due to their use in different processes, but one of the most important and efficient protocols is the multicomponent Petasis-borono-Mannich (PBM) reaction [17-19]. In this approach, an amine, an aldehyde, and a boronic acid react to give access to a new amine... 

Asymmetric synthesis of anti-1,2-amino alcohols via the borono-Mannich reaction a formal synthesis of (-)-swainsonine. 

N. Selander, A. Kipke, S. Sebehus, K. J. Szab6, J. Am. Chem. Soc. 2007, 129, 13723-13731. Petasis borono-Mannich reaction and allylation of carbonyl compounds via transient allyl boronates generated by palladium-catalyzed substitution of aUyl alcohols. An efficient one-pot route to stereodefmed a-amino acids and homoaUyl alcohols. 

A. Yazici, Pure Appl. Chem. 2008, 80, 751-762. Exploiting the borono-Mannich reaction in bioactive alkaloid synthesis. 

PBM Petasis-borono-Mannich TMSCN trimethylsilyl cyanide... 

Scheme 6.39 General mechanism for the Petasis borono Mannich reaction [54].

In 2003, Portlock and coworkers [53a] demonstrated that the Petasis borono Mannich (three-component) condensation can be performed in tandem with the Ugi (four-component) condensation to provide access to six-dimensional libraries of compounds with application in the drug discovery area. 

Petasis Borono-Mannich Reaction Iminium Ions Lacking Neighboring Heteroatom Functionality... 

Scheme 7.1 Discovery of the Petasis borono-Mannich reaction using paraformaldehyde, amines and alkenylboronic acids.

Subsequent to this, there have been numerous reports of the use of this reaction using alkenyl, alkynyl and arylboronic adds or esters in reactions with a range of amines and aldehydes. This reaction has been variously named the boronic Acid Mannich , boronic Mannich , boro-Mannich , Petasis boronic acid-Mannich , Petasis borono-Mannich , and Petasis" reaction. The more indusive term of Petasis borono-Mannich reaction will be used throughout this chapter. 

Harwood and co-workers have reported the reaction of 3 and 2-furylboronic acid with aliphatic aldehydes (Scheme 7.2) [25,26). Adducts 4 were obtained in good yields and high diastereoselectivities, and are valuable intermediates for the formation of a-amino acids. This is an interesting reaction, since not only was it the first example of a stereoselective Petasis borono-Mannich reaction, but it also represents a rare example of the successfixl use of simple aliphatic aldehydes. Its success may be due to the... 

Scheme 7.2 Petasis borono-Mannich reaction of 2-furylboronic acid, aldehydes and secondary amines.

Synthetic Benefits of the Petasis Borono-Mannich Reaction... 

An inherent advantage of the Petasis borono-Mannich reaction is the ability to conduct reactions in a three-component fashion, since the imine or iminium ion intermediates can be formed in situ from the condensation of either primary or secondary amines with the corresponding aldehydes or ketones. The operational advantages of such a three-component coupling approach, combined with the practical benefits outlined above, render the Petasis borono-Mannich reaction particularly desirable for parallel synthesis applications and in the generation of combinatorial libraries. In-... 

There are no reports of detailed mechanistic studies on the Petasis borono-Mannich reaction. Nevertheless, some experimental observations have been made that provide a basic understanding of the reaction. These observations also provide some useful guidelines as to the types of substrates that are suitable for participation in the Petasis borono-Mannich reaction. 

Figure 7.3 Putative coordinated intermediates involved in Petasis borono-Mannich reactions of aldehydes possessing neighboring heteroatoms.

Microwave acceleration of reactions is a valuable tool for organic synthesis [39], and various specialized instruments are now commercially available. Tye and co-workers have reported the microwave-assisted Petasis borono-Mannich reaction of arylboron-ic acids and primary or secondary amines with either glyoxylic acid or salicylaldehyde [40]. Optimized reaction conditions employed didiloromethane as solvent, and microwave assisted heating at 120 °C for 10 min. Products were obtained in generally modest yields (10-83%), in part due to incomplete reaction conversion imder the reported conditions. 

A similar approach has been outlined by Petasis and Patel for the formation of piperazinones and benzopiperazinones, using either stepwise or one-pot" protocols (Scheme 7.5) [41], A sequential protocol was used for reactions of mono-Boc protected ethylenediamines, 1,2-cyclohexanediamines or 1,2-phenylenediamines 19. Standard conditions were used for the Petasis borono-Mannich reaction, followed by Boc... 

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