Vinylboronic acid

The utility of the Suzuki reaction in the challenging arena of natural product total synthesis has been explored. The constitution of bombykol (106) (see Scheme 26), a well-known pheromone, lends itself to a Suzuki coupling. Indeed, in a short stereospecific synthesis of 106, Suginome et al. demonstrated that ( )-vinylboronic acid ( )-104 can be smoothly cross-coupled with (Z)-l-pentenyl bromide [(Z)-105] 44 the configurations of both coupling partners are preserved in the C-C bond forming process. 

The adducts derived from catechol borane are hydrolyzed by water to vinylboronic acids. These materials are useful intermediates for the preparation of terminal vinyl iodides. Since the hydroboration is a syn addition and the iodinolysis occurs with retention of the alkene geometry, the iodides have the -configuration.214... 

Through the use of arenediazonium salts, the straightforward transformation of amines into cross-coupling products can be realized. Whenever the diazonium salts do not tolerate bases and strong nucleophiles (e.g., phosphines), base- and phosphine-free protocols have to be used. Heterocyclic carbene ligands serve well in cross-coupling of Aryl- and vinylboronic acids, or alkylboronates with arenediazonium salts.369,370 Several convenient phosphine-free protocols have been developed for the same purpose.371-373... 

A series of remarkable stoichiometric CH functionalization reactions have been employed, including transmetalla-tion with a vinylboronic acid moiety, to synthesize the core of teleocidin B-4 (Equation (200)).1... 

The Mannich reaction of secondary amines with paraformaldehyde and vinylboronic acids gives excellent yields of pure (E)-allylamines, e.g. equation 63181. 

Kabalka and co-workers reported the direct cross-coupling of cinnamyl alcohols with aryl- and vinylboronic acids using simple rhodium salts in an environmentally benign ionic liquid medium (Eq. 6) [30]. The ability to utilize allylic alcohols, without activation, is significant from the viewpoint of atom economy, yet challenging due to the poor leaving group ability of hydroxide. 

When vinylboronic acids are used as reactants, bases, especially Tl(OH)3, can accelerate the reaction.143 Scheme 8.11 gives a number of examples of coupling using organoborane reagents. 

The Heck reactions of thiophenes, particularly in the 2-position are well documented. In a recent example 2-bromothiophene was converted into a thienyl-vinylboronic acid derivative using a conventional palladium-triphenylphosphine catalyst and tributylamine as base (6.59.),... 

Vinylboronic acids have found use in a multicomponent one-step synthesis of a-amino acids (see question 24). The HOMO and LUMO of the parent compound, CH2=CHB(OH)2, from an SHMO calculation are... 

With the TES protected alcohol at C-19 and the free alcohol at C-15 the subsequent reactions could be performed. Hydroboration of the triple bond and aqueous work-up creates vinylboronic acid 10, which is the other coupling partner with 6. 

Cross-coupling reactions with vinylboronic acids can yield either the normal product (ipso-substitution of boron) or a regioisomer formed via a Heck-type reaction (cine-substitution Scheme 8.17) [135]. Formation of the normal product (1-phenylhexene in Scheme 8.17) requires a base capable of binding to the boronic acid, thereby increasing the nucleophilicity of the boron-bound carbon atom (typically ROM, MOH, M2C03, M3P04, where M= alkali metal [136]). Products of cine-substitution result when tertiary amines are used as bases, i.e. under Heck-type reaction conditions. 

Scheme 8.17. Regioselectivity of cross-coupling reactions with vinylboronic acids and vinylstannanes [9, 144].

Z,E)-2-Bromo-l,3-dienes. 1,1-Dibromoalkenes and E-vinylboronic acids couple to (Z,E)-2-bromo-1,3-dienes in the presence of this Pd(0) catalyst and TlOH as base, conditions developed earlier for coupling of vinyl bromides with vinyl-... 

Dihydro-277-thiopyran-6-yl trifluoromethanesulfonate undergoes a carbonylative Suzuki-Miyaura coupling with vinylboronic acids to give substituted 1 -(3,4-dihydro-2//-thiopyran-6-yl)prop-2-cn-l -ones together with minor amounts of the non-carbonylated coupled products <2007EJ02152>. 

Silver salts are also common activators in numerous Suzuki coupling reactions. The earliest example could probably be found in the Kishi s palytoxin synthesis. Silver oxide as well as thallium hydroxide provided dramatic rate enhancements in the couplings of vinylboronic acids (Scheme 10.41).69 Both thallium and silver ions are most probably abstracting halide in palladium intermediates, but silver is clearly the most efficient. Moreover, with the right counterion, the silver salt also acts as a mild base and activator. 

Radioiodination of vinylboronic acid derivatives has been applied443-445 for the synthesis of 17 tf-iodovinylestradiol derivatives443 (equations 206) and (E)-1 -[123I]iododecene, 306 (equation 207). In the iodination of a vinylboronic acid, chloramine-T has been found to be the most efficient oxidant under both carrier-added and NCA conditions and has been applied in reaction 207. 

Vinylboronic acids react with iodine927 or iodine supported on alumina (equation 136)928. 

This is an indirect method to obtain an anti Markovnikov addition of HI to terminal acetylenes. Chlorination929 and bromination930 (with bromine or with sodium bromide931) of vinylboronic acids results in inverted vinyl halides. This allows the three-step stereospecific inversion of ( )vinyl bromide into the [Z] isomer (equation 137)932. 

Trialkylboranes were converted into alkyl phenyl selenides and alkyl phenyl tellurides by reactions with PhSeSePh and PhTeTePh in the presence of stoichiometric amounts of air.550 Vinyl selenides and tellurides were synthesized by treating vinylboronic acids or esters with phenylselenyl chloride in ionic liquids (Equation (114))551 or by palladium-catalyzed coupling reaction of diorgano ditellurides (Equation (115)).552... 

Multi-component procedures based upon the Mannich reaction and boron reagents were reported in 1993 as a reaction between vinylboronic acids and the adducts of secondary amines and paraformaldehyde (Table 5, entries 1 and 2).558... 

The boron-Mannich condensation was assisted by a hydroxy group adjacent to the aldehyde moiety. The products derived from salicylaldehydes and vinylboronic acids underwent cyclization to 2H-chromene derivatives with elimination of the amine upon heating (Equation (119)).566... 

Based on our experience in using A1203 as base in the iodination15 and bromination16 of vinylboronic acids, we hoped that this solid would likewise function as base in the Suzuki reaction. To simplify the reaction, we hoped to use ligandless palladium black [Pd(0)] as catalyst, thus alleviating the need for expensive or custom-made phosphine ligands. 

The cross-coupling of allyl alcohols with aryl- and vinylboronic acids has been accomplished in [C4Ciim][BF4] and [C4Ciim][PF6] with rhodium catalysts.1"31 While no reaction takes place in polar solvents such as water or DMF, good results were obtained in [C4Ciim][PF6], see Scheme 6.12, and rhodium(I) as well as rhodium(III) compounds worked well in the latter solvent. The presence of copper salts as well as acids led to an increase of the reaction rate. 

---