Protection of boronic acids

The phenyl group became a practical protective group for carboxylic acids when Sharpless published a mild, effective one-step method for its conversion to a carboxylic acid. It has recently been used in a synthesis of the amino acid statine, where it served as a masked or carboxylic acid equivalent.  

The furan group also serves as a protected carboxylic acid. It is more readily converted to an acid in most cases. 

Boronic esters are easily prepared from a diol and the boronic acid with removal of water either chemically or azeotropically (see Protection of Diols). Sterically hindered boronic esters such as those of pinacol can be prepared in the presence of water. Boronic esters of simple unhindered diols are quite water-sensitive and readily hydrolyze. On the other hand, those very hindered esters such as the pinacol and pinanediol derivatives are very difficult to hydrolyze and often require rather harsh conditions to achieve cleavage. 

phenylboronic acid. Cleavage occurs by transesterification. 

CH2CI2, 8 h, 83% yield. BBri has also been used but also results in BOC cleavage.  

---

Although boronates are quite susceptible to hydrolysis, they have been useful for the protection of carbohydrates. Note that as the steric demands of the diol increase, the rate of hydrolysis decreases. For example, pinacol boronates are rather difficult to hydrolyze in fact, they can be isolated from aqueous systems with no hydrolysis. The section on the protection of boronic acids should be consulted. 

A synthetic procedure 33 has been developed for the preparation of boronic acids with a protected aldehyde side chain, 2-(l,3-dioxolan-2-yl)ethyl, which is readily converted into boroOrn peptides similar to 30. Peptides containing boroLys were prepared by a series of reactions analogous to those used for the preparation of 30 except 4-bromobut-l-ene was used as starting material in place of 3-bromoprop-l -ene 36 ... 

As a consequence of the mild reaction conditions in the sequence to 3-halo furans 55 the palladium catalyst should be still intact to trigger another Pd-catalyzed coupling in the sense of a sequentially Pd-catalyzed process [31]. As a consequence, a sequential Sonogashira-deprotection-addition-cyclocondensation-Suzuki reaction, where the same catalyst system is applied in two consecutive significantly different cross-coupling reactions in the same reaction vessel should be feasible. Therefore, upon consecutive reactions of (hetero)aroyl chlorides 7 and THP-protected propargyl alcohols 54, Nal and PTSA, and finally, addition of 1.05 equiv of boronic acids 60 and sodium carbonate, the substituted 3-aryl furans 61 can be obtained in decent yields (Scheme 35). 

Emergency protection All CPS control rods (48) are inserted into the core by gravity when their drives are deenergized by a protection system signal. System of emergency injection of boron acid solution... 

Recently, Woodward s group [22] reported that bis-sulfamoyl imines are potentially ideal substrates for the Rh-catalyzed asymmetric additions of boronic acids because of (i) near-perfect enantioselectivities (11 examples, 98% to 99% ee), (ii) good-to-excellent diastereoselectivities (10-32 1 r c/meso )> and (iii) high functional group tolerance in the removal of the protecting group via mild heating in aqueous pyridine (Scheme 6.17). 

Figurel.43 Examples of the use of boronic acids forthe protection of diol compounds.

The combination of rhodium catalysts and organoboronic acids has emerged recently as a powerful and ideal catalytic system in carbon-bond forming reactions. This tremendous system overcomes the functional group protection issue, but can also apply to catalytic asymmetric synthesis, which can provide much chiral product using a small amount of a chiral catalyst. This chapter reviews the development and scope of the rhodium-catalyzed addition of boronic acids to organic electrophiles [1]. 

Differendy from the above-described strategies, Montgomery and collaborators [86] disconnected aigialomycin D at the C7 -C8 double bond to propose a nickelalternative approach to RCM. The synthesis commenced with the preparation of boronic acid 213, which was next engaged in a Suzuki coupling with iodide 211. Selective monodesilylation of the protected diol 214 followed by Dess-Martin oxidation afforded the key aldehyde 210a, which was cyclized with Ni(COD)2 and IMes to provide a mixture (1 1) of diastereomers. Global deprotection followed by the separation of isomers finally... 

Sibi and co-workers described an easy access to enantioenrichied (3-amino acids through a rhodium-catalyzed 1,4-addition of boronic acids 76a-c to A-protected a-aminomethylmethacrylate 75 in the presence of Difluorophos as a chiral ligand.The corresponding p-amino acids derivatives 77a-c could be obtained in up to 95% yield with 91% ee (Scheme 31.27). 

The solid appears to be a mixture of the complexes CH,COOH.BF, and 2CH COOH.BF,. The latter appears to be a liquid and is alone soluble in ethylene dichloride the former is a solid. The solid moiioocetic acid complex is obtained by saturating an ethylene dichloride solution of acetic acid with boron trifluoride, filtering and washing the precipitate with the solvent it is hygroscopic and should be protected from moisture. It may be used as required 0-75 mol is employed with 0-26 mol of ketone and 0 6 mol of anhydride. 

The Suzuki coupling of arylboronic acids and aryl halides has proven to be a useful method for preparing C-aryl indoles. The indole can be used either as the halide component or as the boronic acid. 6-Bromo and 7-bromoindolc were coupled with arylboronic acids using Pd(PPh3)4[5]. No protection of the indole NH was necessary. 4-Thallated indoles couple with aryl and vinyl boronic acides in the presence of Pd(OAc)j[6]. Stille coupling between an aryl stannane and a haloindole is another option (Entry 5, Table 14.3). 

Thioketals are readily formed by acid-catalyzed reaction with ethane-dithiol. Selective thioketal formation is achieved at C-3 in the presence of a 6-ketone by carrying out the boron trifluoride catalyzed reaction in diluted medium. Selective protection of the 3-carbonyl group as a thioketal has been effected in high yield with A" -3,17-diketones, A" -3,20-diketones and A" -3,l 1,17-triones in acetic acid at room temperature in the presence of p-toluenesulfonic acid. In the case of thioketals the double bond remains in the 4,5-position. This result is attributed to the greater nucleophilicity of sulfur as compared to oxygen, which promotes closure of intermediate (66) to the protonated cyclic mercaptal (67) rather than elimination to the 3,5-diene [cf. ketal (70) via intermediates (68) and (69)]." " ... 

---