Petasis boronic esters

R.A. Batey and co-workers developed a modification of the Petasis-boronic acid-Mannich reaction that occurs via N-acyliminium ions derived from A/-protected-2,3-dihydroxypyrrolidine and 2,3-dihydroxypiperidine derivatives. This method was utilized in the total synthesis of (+)-deoxycastanospermine. The formation of the A/-acyliminium ion was achieved by treating A/-Cbz-2,3-pyrrolidine with BF3-OEt2. ° Subsequent vinyl transfer from the alkenylboronic ester provided the product with excellent yield and diastereoselectivity. 

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 ... 

In its most general form, the boronic acid Mannich or Petasis reaction18 involves the reaction of boronic acid 22, a carbonyl compound 8, and an amine 23 to produce secondary amines 24. If one uses a-keto acid 25 for the carbonyl component then the corresponding product from the Petasis reaction was a-amino acid 26. The key mechanistic step was proposed to occur intramolecularly with alkyl migration from intermediate boronate ester 28 formed from aminol 27. 

Boronic acids bearing strong electron-poor aromatic groups (such as pyridinyl) were reported to lack reactivity in the Petasis-Akritopoulou reaction, using standard conditions (dichloromethane, room temperature) [54]. Boronic esters were also studied [57] and the authors reported that the mechanism of formation of the boronate species was different from that with phenylboronic acid derivatives. Piettre and coworkers considered the use of hexafluoro-iso-propyl alcohol (HFIP), which is an alcohol with higher ionizing power, as the solvent in the Petasis-Akritopoulou reaction with boronic esters (Scheme 6.43). Compared to the use of methanol as solvent and microwave-assisted irradiation (MW), the yields were much higher (a maximum of 99% yield was obtained ) [58]. 

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. 

Boronic esters will also react under appropriate circumstances. Petasis used bis(isopropyl) (2B)-bromoethenylboronic ester in a reaction with glyoicyUc acid and aminodiphenylmethane [34]. Scobie and co-workers have reported the coupbng of pinacolyl aryl and alkenylboronic esters with secondary amines (38). The reaction gave good yields with alkenylboronic esters (70-82%), but worked poorly with aryl-boronic esters (0-12%). In contrast to the above results, the reaction did not proceed with primary amines under the same conditions. 

The use of chiral boronic esters in the Petasis borono-Mannich reaction has been reported to result in low levels of enantioselectivity of the adducts at room temperature (6-15% ee) [48]. Auxiliaries used in this study by Scobie and co-workers included pinanediol and tartaric acid derived alkenylboronates. Morpholine was the only secondary amine used, with the primary amine ethyl glycinate failing to react. 

The dihydroxybiaryl 97 can be used to exchange with alkenylboronate esters, bringing chirality in close proximity to the reaction site when the boronates participate in a Petasis reaction to build ally lie amines/ ... 

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... 

The Petasis reaction is a multicomponent condensation occurring between boronic acids, amines and aldehydes. The asymmetric version of this reaction is very attractive for the synthesis of chiral a-amino acids.In this context, Schaus and Lou reported the use of chiral biphenols as organocatalysts for the asymmetric Petasis reaction of ( )-diethyl styrylboronate with secondary amines and ethyl glyoxylate. The corresponding a-amino esters were obtained in high yields and enantioselectivities of up to 97% ee by using a vaulted biaryl phenol such as (5)-VAPOL as the organocatalyst in the presence of 3-A molecular sieves (Scheme 2.59). 

Three-component Petasis reactions among salicylaldehydes, amines, and organo-boronic acids have been catalysed with a chiral thiourea BINOL catalyst to prepare alkylaminophenols with yields and ee values of up to 92% and 95%, respectively. Formation of amino esters Et02CCH(Ar)NR2 by Petasis combination of Et02CH0, R2NH, and ArB(OH)2, catalysed by Cu(I), is believed to involve transmetallation from boron to copper from which Ar is delivered intramolecularly to the iminium group of the coordinated intermediate. ... 

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