Boron conjugated addition

Electron-deficient acetylenes, silylformylation, 11, 483 Electron-deficient substrates, Pauson—Khand reaction, 11,353 Electron-deficient unsaturated bonds boron conjugate additions, 9, 214 cycloadditions to, 9, 314... 

Representative procedure for NHC-Cu-catalyzed enantioselective boron conjugate additions. Preparation of the desired NHC-Cu-0-t-BiP ... 

Boron Conjugate addition of alkenylboronic acids PhCH=CHB(OH)2 and alkynylboronic esters to ArCH=CHCOMe (Ar = unprotected indoles), carried... 

In 2010, Hoveyda and coworkers disclosed a Cu-catalyzed method for enantio-selective boronate conjugate additions to trisubstituted alkenes of acyclic a.P Unsaturated carboxylic esters, ketones, and thioesters, resulting in the formation of p-substituted quaternary carbon stereogenic centers (Scheme 3.65) [94]. By using 5 mol% of a chiral monodentate NHC 103 copper complex at low temperature, the products were obtained in good yields (up to 98%) and enantiose-lectivities (up to 96% ee). Moreover, transformations involving unsaturated thioesters gave the best enantiocontrol. 

The proposed model that explains the results for the NHC-copper-catalysed boronate conjugate addition reaction is represented in Fig. 20. Complex T provides a rationale for the levels and trends in selectivity. Alkene coordination likely occurs such that the Cu-B bond is aligned with the substrate ir, whilst the carbonyl moiety resides proximal to the NHC s monosubstituted N-Ar unit (vs U). 

Lee K, Zhugralin AR, Hoveyda AH. Efficient C—B bond formation promoted by N-heterocychc carbenes synthesis of tertiary and quaternary B-substituted carbons through metal-free catalytic boron conjugate additions to cyclic and acyclic a,p-unsaturated carbonyls. J Am Chem Soc. 2009 131 7253-7255. 

Wu H, Radomkit S, O Brien JM, Hoveyda AH. Metal-free catalytic enantioselective C—B bond formation (pinacolato)boron conjugate additions to a,p-unsaturated ketones, esters, Weinreb amides, and aldehydes promoted by chiral N-heterocychc carbenes. J Am Chem Soc. 2012 134 8277-8285. 

Conjugate additions of alkylcopper- boron trifluoride to enoates of sulfonamide-shielded alcohols (6 and 7) quite generally proceeded with >99% de and >90% yield30. The following general trend has emerged from the reactions of 6 and 7. 

The asymmetric 1,4-conjugate addition of phenyl boronic acids to cyclohex-2-enone was catalysed by the Pd complex 141 (Fig. 2.25). Good to excellent yields and high ee (90-97%) were obtained under mild conditions and low catalyst loadings (rt, 3 mol%)... 

Fig. 2.25 Palladium catalysts and postulated intermediates in the asymmetric conjugate addition of phenyl boronic acids to cyclohex-2-enone...

The medicinal chemists subsequently discovered an improved route to racemic acid 9 that started with 2-bromo-2-cyclopente-l-one 11 (Scheme 7.2) [5]. Suzuki-Miyaura cross-coupling of 11 with 4-fluorophenyl boronic acid 12 provided 13 in 67% yield. Conjugate addition of cyanide furnished ketone 14 in 71% yield. Reduction of 14 with NaB H4 gave a 2.8 1 mixture of desired 15 and undesired 16 which were separated by silica gel chromatography. The observed diastereoselec-tivity with the cyano group was similar to ester 6. Hydrolysis of 15 with 5 M NaOH in MeOH gave racemic acid 9 in 91% yield, which was resolved as outlined in Scheme 7.1. 

Keywords Atom transfer reactions Boron C C bond formation Conjugate addition Radical initiators Radical reaction Tin-free... 

Brown proposed a mechanism where the enolate radical resulting from the radical addition reacts with the trialkylborane to give a boron enolate and a new alkyl radical that can propagate the chain (Scheme 24) [61]. The formation of the intermediate boron enolate was confirmed by H NMR spectroscopy [66,67]. The role of water present in the system is to hydrolyze the boron enolate and to prevent its degradation by undesired free-radical processes. This hydrolysis step is essential when alkynones [68] and acrylonitrile [58] are used as radical traps since the resulting allenes or keteneimines respectively, react readily with radical species. Maillard and Walton have shown by nB NMR, ll NMR und IR spectroscopy, that tri-ethylborane does complex methyl vinyl ketone, acrolein and 3-methylbut-3-en-2-one. They proposed that the reaction of triethylborane with these traps involves complexation of the trap by the Lewis acidic borane prior to conjugate addition [69]. 

Several attempts to take advantage of the intermediate boron enolate to achieve tandem conjugate addition-aldol reaction have been proposed [71]. Recently, Chandrasekhar [72] reported the addition of triethylborane to methyl vinyl ketone followed by the in situ trapping of the enolate by aromatic aldehyde (Scheme 26). 

Tandem processes mediated by triethylborane involving conjugate addition to enones followed by aldol reaction are reported (Scheme 52, Eq. 52a). More recently, a tandem process involving addition of an isopropyl radical to an o ,/3-unsaturated oxime ether afforded an azaenolate intermediate that reacts with benzaldehyde in the presence of trimethylaluminum. The aldol product cyclizes to afford an isopropyl substituted y-bulyroloaclonc in 61% overall yield (Scheme 52) [116]. In these reactions, triethylborane is acting as a chain transfer reagent that delivers a boron enolate or azaenolate necessary for the aldolization process. 

Recent theoretical studies of reductive elimination from MeaCu-S in the presence of BF3 suggest that reaction rate of the conjugate addition can increase if one of the Me groups is detached from the copper(III) to bind with a boron atom (Scheme 10.12) [129]. 

When the metallic additive to the intermediate 374 was zinc dihalide (or another Lewis acid, such as aluminum trichloride, iron trichloride or boron trifluoride), a conjugate addition to electrophilic olefins affords 381 . In the case of the lithium-zinc transmetallation, a palladium-catalyzed Negishi cross-coupling reaction with aryl bromides or iodides allowed the preparation of arylated componnds 384 ° in 26-77% yield. In addition, a Sn2 allylation of the mentioned zinc intermediates with reagents of type R CH=CHCH(R )X (X = chlorine, bromine) gave the corresponding compounds 385 in 52-68% yield. ... 

Hayashi and co-workers established the catalytic cycle of the asymmetric conjugate addition in 2002 [16]. An example is outlined in Scheme 3.4 for the reaction of phenylboronic acid 2m with 2-cyclohexenone la. The reaction has three main intermediates hydroxo-rhodium (A), phenylrhodium (B), and oxa- j-allylrhodium (C) complexes. They are related in the catalytic cycle by (1) transmetallation of a phenyl group from boron to hydroxo-... 

Oi and Inoue recently described the asymmetric rhodium-catalyzed addition of organosilanes [35]. The addition of aryl- and alkenyltriaUcoxysilanes to u,y9-unsaturated ketones takes place, in the presence of 4 mol% of a cationic rhodium catalyst generated from [Rh(COD)(MeCN)2]BF4 and (S)-B1NAP in dioxane/H20 (10 1) at 90°C, to give the corresponding conjugate addition products (Eq. 3). The enantioselectivity is comparable to that observed with the boronic acids, as the same stereochemical pathway is applicable to these reactions (compare Scheme 3.7). 

Scheme 3.18 Rhodium-catalyzed asymmetric conjugate addition of 6-Ph-9BBN forming boron enolate [37].

The addition of Rh-Csp a-bonds to enones is a well-studied process. Lee s reaction is predicated on the idea that rhodium-catalyzed conjugate addition of boronic acids to enones can be interrupted by 1,1-insertion into an alkyne. Thanks to the high reactivity of rhodium toward alkynes and the effects of tethering, a partly intramo-... 

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