Allylic Boronic Acids

Because of their tremendous utihty as carbonyl aUylation agents (Section 1.5.3.2), several methodologies have been developed for synthesizing allyHc boronic acids and their various esters. The preparation and reactions of aUylic boronic esters are discussed in detail in Chapter 6. 

Chemoselective Transformations of Compounds containing a Boronic Add (Ester) Substituent 

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Allyl tetrafluoroborates are also useful allylboration reagents. They can be made from allylic boronic acids and are stable solids.63 The reaction with aldehydes is mediated by BF3, which is believed to provide the difluoroborane by removing a fluoride. The addition reactions occur with high stereoselectivity, indicating a cyclic TS. 

The cross-coupling reaction of bis(pinacolato)diborane(4) [(Me4C202) B-B(02C2Me4)] with allyl acetates provided the pinacol esters of allyl-boronic acids with common structure 74 with regio- and fi-stereoselectively in high yields as 75-84 have been reported (Scheme 15). The reaction was efficiently catalyzed by Pd(dba)2 in DMSO at 50 °C.66... 

Theoretical support was obtained to explain the experimental results observed with a-chloro- or a-bromo-substituted pinacolboronates (5)6 (Scheme 3.IX). When calculations were performed on the reaction between the a-fluoro-substituted allyl-boronic acid and formaldehyde, transition state A, in which fluorine atom occupies an axial position, was found to be more stable than transition state B by 3.5 kcal/mol. 

A less extensive study of the reaction of boronic acids with different structural characteristics - aryl, vinyl, allyl, and alkyl- with iodobenzene on Pd-KF/Al203 was also undertaken (eq. 3) (Table 4), Only the allylic boronic acid, 3-propenylboronic acid, did not undergo the Suzuki coupling although it was largely consumed. 

The central catalytic cycle is characterized by the use of the pincer complex XVII. The authors supposed that the boronate group is transferred from diboronate XIII to catalyst XVn, affording the jj -boronato complex XVIII. The boronato group substitutes the activated hydroxyl group in XV to give allyl boronic acid XVI and boric acid. Importantly, this step ensures that the waste product of the reaction is non-toxic boric acid. 

The combination of metal tuning and double stereodifferentiation helps to prepare chelation and nonchelation products in the imine series7. In the case of an alkoxy substituent adjacent to the aldimino, the chelation product 10 is predominantly obtained with allylmagnesium chloride, chloromagnesium allyltriethylaluminate or allylzinc bromide, while the use of allyl-boronates or allyltitanium triisopropoxide, which lack the requisite Lewis acidity for chelation, gives 11 with good Cram selectivity. 

Petasis reported an efficient addition of vinyl boronic acid to iminium salts.92 While no reaction was observed when acetonitrile was used as solvent, the reaction went smoothly in water to give allyl amines (Eq. 11.54). The reaction of the boron reagent with iminium ions generated from glyoxylic acid and amines affords novel a-amino acids (Eq. 11.55). Carboalumination of alkynes in the presence of catalytic Cp2ZrCl2 and H2O affords vinylalane intermediates, which serve as nucleophiles in the subsequent addition to enantiomerically enriched... 

The use of tartrates as chiral auxiliaries in asymmetric reactions of allenyl bor-onic acid was first reported by Haruta et al.69 in 1982. However, it was not for several years that Roush et al.,70 after extensive study, achieved excellent results in the asymmetric aldol reactions induced by a new class of tartrate ester based allyl boronates. 

Starting from substituted allyl bis-(2,4-dimethyl-3-pentyl)-L-tartrate boronic acid, synthesis of a,/l-disubstituted tetrahydrofurans (134, n = 1) or tetrahydropyrans (134, n = 2) can be accomplished with high enantioselectivity (Scheme 3-46).79... 

The allyl boronate esters (R,R)- and (S,S)-1 are prepared by reaction of allylboronic acid, CH2=CHCH2B(OH)2 with l- and D-diisopropyl tartrate.1... 

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 addition of allylic boron reagents to carbonyl compounds first leads to homoallylic alcohol derivatives 36 or 37 that contain a covalent B-O bond (Eqs. 46 and 47). These adducts must be cleaved at the end of the reaction to isolate the free alcohol product from the reaction mixture. To cleave the covalent B-0 bond in these intermediates, a hydrolytic or oxidative work-up is required. For additions of allylic boranes, an oxidative work-up of the borinic ester intermediate 36 (R = alkyl) with basic hydrogen peroxide is preferred. For additions of allylic boronate derivatives, a simpler hydrolysis (acidic or basic) or triethanolamine exchange is generally performed as a means to cleave the borate intermediate 37 (Y = O-alkyl). The facility with which the borate ester is hydrolyzed depends primarily on the size of the substituents, but this operation is usually straightforward. For sensitive carbonyl substrates, the choice of allylic derivative, borane or boronate, may thus be dictated by the particular work-up conditions required. 

The Lewis acid catalyzed reactions expand the scope of aldehyde substrates with certain boronate reagents. For example, whereas cyclohexanecarboxalde-hyde is unreactive nnder thermal (nncatalyzed) conditions, it does react with allylic boronate 8 nnder Sc(OTf)3 catalysis at room temperature (Eq. 53, see also Eq. 6).26... 

The use of chiral Br0nsted acids is illustrated in Eq. 93 as a method for catalyst-controlled double diastereoselective additions of pinacol allylic boronates. Aside from circumventing the need for a chiral boronate, these additions can lead to very good amplification of facial stereoselectivity. For example, compared to both non-catalyzed (room temperature, Eq. 90) and SnCU-catalyzed variants, the use of the matched diol-SnCU enantiomer at a low temperature leads to a significant improvement in the proportion of the desired anti-syn diastereomer in the crotylation of aldehyde 117 with pinacolate reagent (Z)-7 (Eq. 93). Moreover, unlike reagent (Z)-ll (Eq. 91) none of the other diastereomers arising from Z- to E-isomerization is observed. 

A similar approach was taken for the synthesis of 45 by Miyaura. " Shaughnessy and Booth synthesized the water-soluble alkylphosphine 46, and found it to provide very active palladium catalysts for the reaction of aryl bromides or chlorides with boronic acids. The more sterically demanding ligand 47 was shown to promote the reactions of aryl chlorides with better results than 46. Najera and co-workers recently reported on the synthesis of di(2-pyridyl)-methylamine-palladium dichloride complexes 48a and 48b, and their use in the coupling of a variety of electrophiles (aryl bromides or chlorides, allyl chlorides, acetates or carbonates) with alkyl- or arylboronic acids very low catalyst loadings at Palladium-oxime catalysts 8a and 8b) have also been developed. In conjunction with... 

Pinacols (61) derived from a variety of aromatic aldehydes have been employed in enantio- and diastereo-selective allylations of aliphatic aldehydes.174 Their allyl-boronate derivatives react under Lewis acid conditions (SnCU) with a variety of aldehyde types, in good yield and ee. Even better results are obtained by addition of (61) as a I irons led acid (auto)catalyst, via coordination/activation of the tin catalyst. 

The same group developed an interesting intermolecular palladium-catalyzed alienation of aryliodide with N-tosyl o-iodoanilines with nucleophiles in combination with two palladium-coupling reactions [69]. In this reaction, the N-allyl(2-iodopalladium)aniline intermediate 52 underwent an intramolecular Heck reaction followed by a cross-coupling reaction with phenyl boronic acid to give the 3,3-disubstituted indoline 53 in 78% yield (Scheme 8.27). 

Jamison has reported the unprecedented nickel-catalyzed assembly of allylic amines 156 from three simple starting materials alkynes, imines, and trialkylbor-anes or boronic acids. The participation of boronic acids in this methodology greatly enhances its synthetic potential, owing to their greater availability (Scheme 8.68) [145]. An asymmetric version of the reaction has also been developed but gave only moderate enantiomeric excesses (33 to 42%). 

Recently, highly functionalized allyl boronates such as 150 were synthesized from allylic acetates 148 and pinacolatodiboron 149. These boronates were employed for the allylation of aldehydes, furnishing the borate esters 151 which undergo lactonization to furnish the a-methylene-7-butyrolactones in high yield and selectivity. The strength of Lewis acids as well as the substituents on the aromatic aldehydes have a profound influence on the stereochemical outcome of the reaction (Scheme 25) <20040L481>. 

Allyl boronates react very slowly with carbonyl compounds as compared to the corresponding allyldialkylboranes, due to the presence of two oxygen atoms on boron which diminish the Lewis acidity of boron. However, the activity of the allyl boronates can be enhanced by the addition of Lewis acid catalysts. There have been two complementary approaches described for the stereoselective allylation with allyl boronates, one involving the use of chiral Lewis acid, and the other involving chiral allyl boronates in conjunction with achiral Lewis acid catalyst. Several chiral fVsymmetric-based 1,2-diols 197 have been employed in combination with SnCLj as a Lewis acid and excellent level of enantioselectivity has been observed for the allylation to furnish homoallylic alcohols 198 with high ee (Equation 8) <2006AGE2426>. 

Alternatively, the allylboration of aldehydes 200 with chiral allyl boronates 199a-d (conveniently prepared from camphorquinone in four steps) also provided the optically active homoallylic alcohols 201a-d with high ee in the presence of achiral Lewis acid catalysts. These boronates are relatively unreactive with aldehydes at low temperatures in the absence of Lewis acid catalyst. However, they furnish low to moderate ee for the allylation at higher temperatures. Hall and co-workers were able to increase the reactivity of the allyl boronates at low temperatures by the addition of strong Lewis acids such as Sc(OTf)3 and obtained the homoallylic alcohols with high ee at low temperatures (Equation 9) <2003JA10160>. 

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