3- alkenylboronic esters

The synthesis of 1-alkenylboronic acids from l-alkenylmagnesiums or -lithiums suffers from difficulty in retaining the stereochemistry of 1-aikenyl halides, but the palladium-catalyzed coupling reaction of diboron 82 with 1-aikenyl halides or tri-flates directly provides 1-alkenylboronic esters (Scheme 1-43) [157, 158]. Although the reaction conditions applied to the aryl coupling resulted in the formation of an... 

The methods for stereocontrolled synthesis of cyclopropylboronic esters have been studied (Scheme 29). The palladium-catalyzed reaction of diazoalkanes (method A), Simmons-Smith reaction (method B), or asymmetric Simmons-Smith reaction using chiral diamines such as 270 (method C) for chiral or achiral 1-alkenylboronic esters... 

The radical addition to 1-alkenyl or 1-alkynylboronic esters or amides took place extremely smoothly because the boron atom stabilizes the resulting ct-radical intermediates. Bu3SnH and PhSH predominated the trans-addition products 287 in the addition to 1-alkynylboronic amides at 90 °G, whereas Bu3SnH and Ph2Ph produced the m-addition products 288 at 0°C (>98% Equation (82)).455 Intramolecular addition to 1-alkenylboronic esters has been demonstrated in boron-tethered radical cyclization that provided 1,3- or 1,4-alkanediols 290 via oxidative workup (Equation (83)).456 Inter- and intramolecular additions of alkyl radical457 and sulfonyl radical458 have also been studied. 

The boron-Wittig reaction has been carried out by bis(boryl)methyllithium 309 generated in situ from tris(boryl)-methane 308 (Equation (91 )).469 The geminal dichromium reagent 3 12470 was found to be an excellent alternative yielding 1-alkenylboronic esters 313470-472 with high //w/ -selectivity (Equation (92)). 

Use as a Chiral Auxiliary Synthesis of Cyclopropylboronic Acids. The chiral dioxaborolane unit can also be used as an effective chiral auxiliary in the synthesis of enantiomerically enriched cyclopropylboronic acids. For example, 1-alkenylboronic esters bearing the tetramethyltartramide group undergo diastereoselec-tive cyclopropanations to afford the cyclopropylboronic acid (eq 11). These products can be used for in situ Suzuki coupling reactions or can be oxidized to produce 2-substituted cyclopropanols. 

The vicinal diol cyclic sulfate from dimethyl tartrate undergoes nucleophilic opening to give substituted malate esters., However, for this application diethyl and diisopropyl L-tartrates give superior yields and selectivities. The asymmetric cyclopropana-tion of the 1 -alkenylboronic ester derived from dimethyl L-tartrate (eq 5) is another example where other tartaric acid derivatives surpass the performance of dimethyl tartrate. ... 

However, the application of these classical procedures for 1-alkenylboronic acid or ester synthesis may suffer from the formation of small amounts of the opposite stereoisomers, or from bis-alkenylation leading to the boronic acid derivatives. Also, formation of trialkylboranes may occur. A recent useful variant utilizes organolithium reagents and triisopropyl borate, followed by acidification with HCl to give directly alkyl-, aryl-, 1-alkynyl-, and 1-alkenylboronic esters in high yields, often over 90% (Scheme 2-6) [27]. Triisopropyl borate was shown to be the best of the available alkyl borates to avoid multiple alkylation of the borates. 

Takahashi, K., Takagi, J., Ishiyama, T., Miyaura, N. Synthesis of 1-alkenylboronic esters via palladium-catalyzed cross-coupling reaction of bis(pinacolato)diboron with 1-alkenyl halides and trifiates. Chem. Lett. 2000,126-127. 

Terminal 2,2-diorgano-1-alkenylboronates (9) are prepared by bromoboration of a terminal alkyne to the /3-bromo-1 -alkenylboronic ester (8) [22], followed by palladium-catalyzed displacement of the /3-halogen with organozinc reagents, which proceeds strictly with retention of configuration [23] (Scheme 2-4). 

In this section, we refer to some Stille reactions that serve as representative examples. As noted before, the Stille reaction is compatible with boronic esters. " Therefore, the Stille cross-coupling provides a simple method for homologation of aryl-and 1-alkenylboronic esters (Scheme 5-60). Since the carbon-boron bond is inert to transmetalation in the absence of a base and oxidative addition of the carbon iodide bond is faster than that of the carbon bromine bond, the arylation of iodoboranes with arylstannanes selectively occurs at the carbon iodo bond without affecting the other onej l In addition. Scheme 5-60 also shows a Stille reaction having a multitude of functional groups such as being present in a modified nucleotide. ... 

The organoborate intermediates can also be generated from alkenylboronic esters and alkyllithium or Grignard reagents, or from ttialkylboranes and alkenyllithium compounds. Conjugated symmetrical and unsymmetrical diynes (289—291), stereochemically pure 1,3-dienes (292,293), and 1,3-enynes (294) including functionali2ed systems can be prepared (289,295). 

Vinylboranes are interesting dienophiles in the Diels-Alder reaction. Alkenylboronic esters show moderate reactivity and give mixtures of exo and endo adducts with cyclopentadiene and 1,3-cyclohexadiene (441). Dichloroalkenylboranes are more reactive and dialkylalkenylboranes react even at room temperature (442—444). Dialkylalkenylboranes are omniphilic dienophiles insensitive to diene substitution (444). In situ formation of vinyl-boranes by transmetaHation of bromodialkylboranes with vinyl tri alkyl tin compounds makes possible a one-pot reaction, avoiding isolation of the intermediate vinylboranes (443). Other cycloadditions of alkenyl- and alkynylboranes are known (445). 

Alkenylboronic esters undergo regio- and stereoselective 1,3-dipolar cycloadditions with nitrones. These reactions lead to boronic ester-substituted isoxazolidines, which can be converted by oxidation with H202 to the corresponding 4-hydroxy derivatives (Eq. 8.48).69 The high selectivity could be the result of a favorable interaction between the boronic ester and the amino group. 

The alkenylboronic esters were synthesized according to a literature procedure [56], Hydrozirconation of alkenylboronic esters with zirconocene hydrochloride, Cp2Zr(H)Cl, prepared by Buchwald s procedure [57], took place smoothly in CH2C12, providing in each case the corresponding borazirconocene 1,1-alkane 18 [34], Addition of propargyl bromide and a catalytic amount of copper(I) cyanide was accompanied by the disappearance of the yellow color associated with these compounds and by carbon—carbon bond... 

To access anti-l,2-diols, indirect methods are required for the preparation of geometrically pure, chiral E-3-alkoxy reagents. To this end, the isomerization of alkenylboronic esters described above (Eq. 41), provides a reliable route to tartrate-derived E-3-siloxy allylboronate 99 (Fig. 7). The latter shows variable enantioselectivities in additions to aldehydes, with cyclohexanecarboxaldehyde affording the highest selectivity (Eq. 70). ... 

Third, chromium-based reagents prepared by reduction of 1,1-dihalo compounds with CrCl2 are suitable for the transformation of aldehydes to (i4)-iodoalkenes, (it)-alkenylsilanes, " and ( )-alkenylboronic esters with one-carbon homologation (Equation (8)). The amount of CrCl2 can be reduced to a catalytic amount by using manganese (or zinc) and MesSiCl. " ... 

In 2006, Ukai et al. proposed an interesting alternative with a rhodium(I)-catalyzed carboxylation of aryl- and alkenylboronic esters proceeding under mild conditions, and leaving ancillary reactive functional groups such as carbonyl- and cyano unreacted [51] (Scheme 5.13). Considering that organoboronic esters are easily available, and that various functional groups are tolerated, this reaction appeared to be particularly useful for the preparation of functionalized arylcarboxylic acids, such as benzoic and cinnamic acid derivatives. 

These boronic esters are easily hydrolyzed to give /ra .v-alkenylboronic acids with complete retention of their stereochemistry (C in Figure 16.15). Alkenylboronic esters and alkenylboronic acids are organometallic compounds that can be alkenylated and arylated in Pd-catalyzed reactions (Section 16.4.2). Aside from this, the iraws-alkenylboronic acid esters as well as the /rau.v-alkenylboronic acids are valuable precursors of haloalkenes (Figure 16.15). 

Haloboration of terminal alkynes yielded stereodefined (Z)-2-halo-l-alkenylboron compounds e.g., 114, 115 that allowed further functionalization of the resulting C-Br or G-B bond. 2,2-Disubstituted-l-alkenylboronic esters were stereoselectively obtained when the haloboration was followed by cross-coupling with 1-alkynylzinc chlorides (Equation (18)).192 The iodoboration-conjugate addition sequence gave alkenyl iodides that were used as intermediate for the total synthesis of deoxyepothilone derivatives (Equation (19)).193-195... 

The catalyzed hydrogenation of alkenylboronic esters was used for the diastereoselective synthesis of alkylboronic esters 276446 (Equation (75)). The hydrogenation of a pyrrolboronic acid provided a prolineboronic acid, which was then resolved by HPLC to give an optically active boronic ester 277447 (Equation (76)). 

Alkenylboranes were proved to be useful traps for nucleophilic alkyl radicals, thus opening attractive routes to diversely substituted alkyl- and alkenylboronic esters (Equations (191) and (192)).457... 

A vinyl halide with an alkenylboronate ester, preserving the stereochemistry of the reagents. 

Z)-vinyl halide ( )-alkenylboronate ester diene with (E, Z) stereochemistry... 

The boronate esters used for Suzuki reactions can be synthesized from commercially available alkyl-, vinyl-, and arylboronic acids. Alkyl and vinyl boronate esters are also synthesized by the hydroboration of double and triple bonds, similar to the hydrobora-tion of alkenes and alkynes in Chapters 8 and 9. Note that the boron atom generally adds to the less substituted end of a double or triple bond. Also, the B and H add to the same side of a triple bond (syn addition) to give a trans alkenylboronate ester. 

The most frequently used metallic catalysts for acyldiazo- and (alkoxycarbonyl)dia-zomethanes are complexes or salts of rhodium, palladium and copper. Alkenylboronic esters A-silylated allylamines and acetylenes are successfully cyclopropanat-ed with diazocarbonyl compounds under catalysis of one of those metal derivatives. Newly developed metallic catalysts for diazoacetic esters include polymer-bound, quantitatively recoverable Rh(II) carboxylate salts ", Cu(II) supported on NATION ion exchange poly-mer ruthenacarborane clusters, Rh2(NHCOCH3)4 which produces cyclopropanes with substantially enhanced trans (anti) selectivity as shown below and (rj -CsHs)... 

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. 

Takai, K., Shinomiya, N., Kaihara, H., Yoshida, N., Moriwake, T., Utimoto, K. Transformation of aldehydes into (E)-l-alkenylboronic esters with a geminal dichromium reagent derived from a dichloromethylboronic ester and CrC. Syn/ett 1995, 963-964. 

Dibromoborane-dimethyl sulfide exhibits high reactivity toward internal alkynes . The relative reactivity of 1-octene, 1-hexyne, (Z)-3-hexene and 3-hexyne is 100, 290, 20 and 5900, respectively. This makes possible selective hydroboration of internal alkynes in the presence of terminal unsaturation. With 1-bromoalkynes Br2HB SMe2 provides [Z]-l-dibromoalkenylboranes which can be transformed into [E]- or [Z]-l-alkenylboronic esters . 

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/ ... 

Hydroboration. Reaction of alkenylboronic esters with catecholborane in the... 

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