Boronic acids, carbonylation

Moderate yields of acids and ketones can be obtained by paHadium-cataly2ed carbonylation of boronic acids and by carbonylation cross-coupling reactions (272,320,321). In an alternative procedure for the carbonylation reaction, potassium trialkylborohydride ia the presence of a catalytic amount of the free borane is utilized (322). FiaaHy, various tertiary alcohols including hindered and polycycHc stmctures become readily available by oxidation of the organoborane iatermediate produced after migration of three alkyl groups (312,313,323). 

After these seminal studies, the use of NHC-Rh systems for the addition of aryl boronic acids to carbonyl compounds became a very fertile area and many groups have reported on variations of this catalytic system [22],... 

Enantioselective D-A reactions of acrolein are also catalyzed by 3-(2-hydroxyphenyl) derivatives of BINOL in the presence of an aromatic boronic acid. The optimum boronic acid is 3,5-di-(trifluoromethyl)benzeneboronic acid, with which more than 95% e.e. can be achieved. The TS is believed to involve Lewis acid complexation of the boronic acid at the carbonyl oxygen and hydrogen bonding with the hydroxy substituent. In this TS tt-tt interactions between the dienophile and the hydroxybiphenyl substituent can also help to align the dienophile.114... 

Carbonylation reactions can be carried out with a boronic acid as the nucleophilic component.251... 

This gives tautomeric mixtures119 when the tert-butyl group is removed. The methyl ether has been used to obtain 3-hydroxy-2-carbonyl derivatives in the selenophene series.120 The unsubstituted 2-hydroxyselenophene system has been prepared by hydrogen peroxide oxidation of 2-selenophene-boronic acid.121 However, in the 5-methyl-substituted system deboronation became such an important side reaction that 5-methyl-2-hydroxyselenophene had to be prepared by acid-catalyzed dealkylation of 5-methyl-2-fert-butoxy-selenophene. Both 2-hydroxy- and 5-methyl-2-hydroxyselenophene exist mainly as 3-selenolene-2-ones (93) and for the 5-methyl derivative it was possible to isolate the / ,y-unsaturated form (92) and follow the tautomeric isomerization. The activation parameters thus obtained were compared with those for the corresponding furan and thiophene systems. 

Ir(OH)(cod)]2 catalyzed a formal [3+2] cycloaddition of 2-formylphenylboronic acid and 1,3-dienes (Scheme 11.41) [50]. The transmetaUation of boronic acid with iridium would yield aryliridium, where the carbonyl group coordinates to the metal. An electrophihc attack of the diene terminus to formyl carbon would then... 

Allylic amine from the three-component reaction of a vinyl boronic acid, a carbonyl and an amine. Also known as boronic acid-Mannich or Petasis boronic acid-Mannich reaction. Cf. Mannich reaction. 

The boron-oxygen mesomeric effect described in the previous section explains the lower reactivity of allylic boronates towards carbonyl compounds compared to that of allylic boranes. The use of Lewis acids, however, allows boronate derivatives, including hindered ones, to react at temperatures comparable to the analogous boranes. As described above (see section Mechanism and Stereochemistry ), the most reactive allylic boronates are those with the most electrophilic boron centers.The nucleophilicity of the y-position of an allylic boron reagent (the position that forms the new C-C bond with the aldehyde) is also important to the reactivity of the reagent. For example, allylic boronates with... 

The concept that acetic acid can be prepared by carbonylation originated in use of routine acids. Carbonylation of methanol was first practiced in a high temperature and pressure process using boron trifluoride or phosphoric acid. A carbon monoxide pressure of 10,000 psi at 300 C was needed for the reaction (10). Metal salts came to replace acids as carbonylation catalysts. Carbonylation of methanol using a metal carbonyl catalyst was first discovered by Reppe and practised later by BASF. However, the process again required high pressure, 7500-10,000 psi, and the selectivity was low (11-14). 

The coupling of the same boronic acid was also achieved with 4-chlorobenzoyl chloride (6.5.), Running the reaction under anhydrous conditions the desired 2-(4 chlorobenzoyl)thiophene was obtained in good yield.7 The opening step in this process is the selective oxidative addition of the palladium into the carbonyl-chlorine bond giving an acylpalladium complex, which on subsequent transmetalation and reductive elimination gives the observed product. 

The enantioselective addition of ally organometallics to carbonyls has become one of the workhorses of organic synthesis. Dennis Hall of the University of Alberta reports (J. Am. Chem. Soc. 125 10160, 2003) the scandium triflate catalysis chiral allylboronic acids become more effective tools. The best of these, the Hoffmann camphor derivative 2, adds to aldehydes under Sc(OTf), catalysis with excellent enantiomeric excess. The reaction works equally well for methallyl, and for the E and Z crotyl boronic acids. The crotyl derivatives react with the expected high diastereocontrol. A limitation to the boronate additions is that branched chain aldehydes give low yields. 

The ketone carbonyl of a series of isatins (63) undergoes enantioselective addition of aryl- and alkenyl-boronic acids, using a rhodium catalyst and a chiral phosphine.180... 

While the above stepwise bimolecular process was well suited for reactions with paraformaldehyde, other aldehydes and ketones did not behave similarly, presumably because of incomplete reactions between the amine and the carbonyl components. To overcome these difficulties, we invented a three-component process (Scheme 7.6) based on the one-step reaction between various amines 38, carbonyls 39, and boronic acids or boronates 40 to give the corresponding amine derivatives... 

The one-step reaction among an amine, a carbonyl and a boronic acid derivative is a highly versatile multicomponent reaction that utilizes readily available compo-... 

The Suzuki coupling reaction of 2-haloselenophenes with boronic acids catalyzed by palladium salt is a new route to prepare 2-arylselenophenes and 2,5-diarylselenophenes in good yields. In addition, 2-arylselenophenyl ketones were also obtained by this protocol from 2-iodoselenophene and boronic acids via a carbonylative process [130],... 

Rhodium-catalyzed addition of boronic acids to enone moiety 89 led to a rhodium-enolate 90 which can be trapped by addition to the adjacent carbonyl function giving functionalized cyclopentanes or cyclohexanes 91. An important feature of this methodology is that this process allows the creation of three contiguous stereocenters with a high level of stereoselectivity. An asymmetric version of this reaction has also been realized with a chiral ligand (BINAP) giving excellent enantiomeric excesses (77 to 95%) (Scheme 34). 

Transition-state inhibitors stably mimic the transition state of the enzymatic reaction, and thereby interact with the substrate-bin-ding and catalytic machinery of the enzyme in a low-energy conformation. Transition-state analogs are competitive, reversible inhibitors, although some have extremely low Kj s and very slow off-rates. All proteases activate a nucleophile to attack a carbonyl, which leads to the formation of a tetrahedral intermediate that then collapses to form the enzyme products—two peptides. Thus, synthetic small molecules that mimic the tetrahedral intermediate of the protease reaction are attractive transition-state analogs. A classic class of protease transition-state inhibitors uses a boronic acid scaffold (4, 10). Boronic acid adopts a stable tetrahedral conformation in the protease active site that is resistant to nucleophilic attack. Boronic acid inhibitors, which are derivatized with different specificity elements, have been developed against every class of protease... 

---