Boron tethers

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. 

An intramolecular version of olefin cross-metathesis has been demonstrated in cyclization of a,u -alkadienes 293462 (Equation (85)), cyclization of enyne to provide 1,3-dienylboronic esters 297406 (Equation (86)), and in cyclization of boron-tethered enynes obtained from 1-alkynylboronates and allylic alcohols (298 463 (Equation (87)) or allyl boronates and propargyl alcohols.464... 

The use of a boron atom as a covalent template for intramolecularizing the Diels-Alder reaction has been relatively little investigated [20-22]. However Narasaka et al. have reported the use of a boronate template to control regio- and stereoselectivity in an IMDA reaction between anthrone 50 and methyl 4-hydroxybut-2-enoate 3 [20a]. Formation of the boronate tether was achieved by simply heating an equimolar mixture of phenylboronic acid with the diene and dienophile at reflux in pyridine with azeotropic removal of water. After 5 h, a single cycloadduct 51 was obtained in 81% yield. The tether was readily removed oxidatively affording the corresponding diol 52 in excellent yield (Scheme 10-19). 

Scheme 10-19 A boronate tether has been used to control the regio- and stereoselectivity of a Diels-Alder reaction.

Although the boronate-tethered triene intermediate was not isolated, its formation can be implied by the lack of any reaction under the same conditions in the absence of PhB(OH)2. The tether also enforces a complete reversal in the regioselectivity of the reaction compared with the analogous intermolecular reactions of acrylates with anthrone [23]. 

Scheme 10-20 Linking the benzocyclobutane and dienophile through a boron tether to form 55 allows interception of the reactive diene formed on ring opening for use in a regioselective IMDA reaction.

Inspired by these results, Nicolaou et al. used a temporary boronate tether to overcome the undesired regiochemical bias in the intermolecular Diels-Alder reaction of diene 56 and dienophile 57, required for their approach to the C-ring of taxol 58 [21a, b, 24], Thermolysis of a benzene solution of 56 and 57 in the presence of PhB(OH)2 under dehydrating conditions provided the cycloadduct 59 in 79% yield (77% conversion) after transacetalization of the boron tether with 2,2-dimethylpropane-l,3-diol and intramolecular acyl transfer to the less strained [4.3.0]bicyclic system. This was further elaborated to an advanced intermediate in the ultimately successful synthesis of taxol (Scheme 10-21) [21c]. 

Scheme 10-21 Nicolaou et al. used a boron-tethered cycloaddition to construct the C-ring of taxol.

A boron-tethered (C-B-O) intramolecular Diels-Alder (IMDA) approach has been used to prepare cyclic alkenyl boronic esters 140 (Scheme 19). Thus, reaction of 2equiv of the dienyl alcohol 138 with 137 in THF, in the presence of molecular sieves, provides the corresponding IMDA precursors 139. The IMDS reaction was then accomplished at 190 °C in a toluene solution, with 5 mol% of 2,6-di-fer7-butyl-4-methylphenol as a free radical inhibitor. Transformation of the carbon-boron bond in 140, using standard organoborane reactions, can then afford a variety of functionalized cyclohexene derivatives <1999JA450>. 

The selective oxidative phenolic orf/io-coupling reaction of simple methyl-substituted phenols turned out to be challenging [12]. When 2,4-dime thy Iphenol (1) is treated by conventional or electro-organic methods, not only the desired biphenol (2) is formed but rather a plethora of polycyclic architectures (Scheme 2) is observed. The major product is Pummerer s ketone (3) and related compounds with a wide structural diversity [13-16]. Application of a boron tether ameliorated the situation tremendously, and biphenol (2) was obtained as the major product [17, 18]. This templated anodic oxidation of 1 represents a multistep process but is suitable for the electro-organic synthesis of (2) on larger scale (see entry Electrosynthesis Using Template-Directed Methods ) [19]. 

In a related process, boron-tethered radical cyclizations are a useful alternative to the widely used silicon versions. In some cases, rearranged products were produced as a result of an intramolecular S i reaction of a carbon-centered radical at boron (Scheme 9.13) [31]. 

DAB= Me02C- N=N— COgMe Scheme9.13 Boron-tethered radical cyclizations. 

Schemc9.22 Boron-tethered intramolecular Diels-Alder reactions.

Chemo- and regioselective ruthenium-catalyzed cyclotrimerization of alkynes was accomplished through a temporary boron tether. Crude aryl boronates were obtained in a one-pot procedure in which they were subjected to a Suzuki-Miyaura coupling with aryl halides (Scheme 9.50) [103]. 

Scheme 2.51 Ru-catalyzed cycloaddition using a temporary boron tether.

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