Ester alkenyl boronic

Alkenylboronic acids, alkenyl boronate esters, and alkenylboranes can be coupled with alkenyl halides by palladium catalysts to give dienes.223... 

The first example of a stable 1,1-bidentate Lewis acid based on boron and zirconium has been reported [35]. The synthesis of 22 is outlined in Scheme 7.12. Treatment of hex-l-yne with HBBr2 Me2S followed by conversion of the dibromoboronic ester to the corresponding alkenyl boronic acid and esterification with propane-1,3-diol provided the alkenyl boronic ester. Hydrozirconation of this compound with 3 equivalents of the Schwartz reagent, Cp2Zr(H)Cl [57], afforded the desired product 22 in 86% yield. 

For both 1 and 2, the synthesis started with the alkenyl amide 3. Salen-mediated conjugate addition proceeded with remarkable induction, to give S in 92% as a mixture of diastereomers. Reduction and cyclization followed by deprotonation and kinetic quench delivered the enantiomerically-enriched cis dialkyl piperidine 6. Homologation of the two sidechains then gave the alkenyl boronic ester 8. 

The major improvement compared to the Rh(I) catalysts was the ability of the Cu(I)/RB (OR )2 system to also carboxylate alkenyl-boronic esters in very good yield, under similar conditions. Interestingly, the system functioned better under ligandless conditions, producing the corresponding unsaturated carboxylic acids in good yields. 

Bromoboration of terminal alkynes 4 into the /J-bromo-l-alkenyl-boronic esters 5 [26], followed by a palladium-catalyzed displacement of the /J-halogen with organozinc reagents [27] is a known strategy for the preparation of metalated diene 6 (Scheme 3). An additional approach is the diboration of symmetrically disubstituted alkynes 7 with bis(pinacolato)diboron 8, followed... 

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>. 

Ni/PCys can catalyse cross-couplings of aryl cyanides with atyl or alkenyl boronic esters in the presence of KOtBu as base and CuFa as additive. The reaction exhibits a wide substrate scope and gives moderate to good product yields (Scheme 14.42). ° ... 

Competition with Heck reaction, q.v., when using an alkenyl boronate ester A. R. Hunt et al, Tetrahedron Letters 34, 3599 (1993). Alternative palladium catalysts G. Marck et ah, ibid. 35, 3277 (1994) T. I. Wallow, B. M. Novak, J. Org. Chem. 59, 5034 (1994). Reviews A. Suzuki, PureAppl. Chem. 63,419-422 (1991) A. R. Martin, Y. Yang, cra Chem. Scand. 47, 221-230 (1993). Cf. Hvdroboration Reaction Stille Coupling. 

Alkenyl boronic esters can also be used to trap nucleophilic carbon-centered radicals, which can be generated by the tin hydride method or by decomposition of an organomercurial derivative. The influence of the olefin and boron substituents on the reactivity and regioselectivity has been determined. Vinyl-9-BBN displayed significantly better reactivity than the boronic ester while the directing effect of the boronic ester group is weaker than that of an ester function. The Barton radical chain procedure furnished very stable adducts due to an intramolecular complexation between boron and nitrogen (Scheme 9.12) [29]. Radical additions of various xanthates also occurred smoothly in the presence of lauroyl peroxide [30]. Intermolecular ver-... 

The adjunction of a P-electron-withdrawing group significantly increased the reactivity of alkenyl boronic esters [54]. The resulting electron-deficient dienophdes were more reactive towards simple 1,3-dienes than simple vinylboronic esters (Scheme 9.23). For instance, the sulfonyl derivative in the presence of cyclopentadiene reacted... 

Alkenyl boronic esters have been shown to be good dipolarophiles in a range of 1,3-dipolar cydoadditions, thus giving access to boron functionalized heterocydes, which can be further engaged in various transformations. 

Scheme 3.57 Synthesis of functionalized alkenyl boronic esters by transmetallation of an alkenyl Crignard reagent with MeO)jB.

Witulski has reported the first hydroboration of 1-alkynylamides. Thus, the hydroboration of ynamide 112 with catechol borane in THF proceeded chemo- and regioselectively yielding only the monohydroboration product, alkenyl boronic ester 113 [90]. However, the isolation of the boronic ester 113 was complicated due to its instability and difficulties of storage and purification. Therefore, it was directly subjected to Suzuki-Miyaura cross-coupling yielding (E)-y3-arylenamide and 3-(2 -amidovinyl)indoles such as 114 (Scheme 3.58). 

Scheme 3.58 Alkenyl boronic esters by hydroboration of functionalized acetylenes.

Synthesis of Functionalized Alkenyl Boronic Esters by Cross-metathesis... 

Danishefsky has applied the cross-metathesis reaction for the synthesis of highly functionalized alkenyl boronate precursor 118 from the terminal olefin 119 and vinyl pinacol boronate in the presence of first generation Grubbs-catalyst 121 [95]. The metathesis reaction was driven to completion by increasing the amount of vinyl boronate ester 120 affording the polyfunctional boronic ester 118 in 93% yield and with exclusive trans-stereochemistry. The alkenyl boronic ester 118 was subsequently used in the synthesis of epothilone 490 via intramolecular Suzuki macrocydization (Scheme 3.62). 

Danishefsky has reported the total synthesis of epothilone 490 (129) via an intramolecular Suzuki macrocyclization of alkenyl boronic ester 130 bearing a terminal alkenyl iodide group [104]. The corresponding alkenyl boronate fragment was prepared by alkenyl boronate cross-metathesis as reported by Grubbs (Scheme 3.69) [105,106]. 

Pietruszka has reported the synthesis of stable enantiomerically pure functionalized cyclopropyl boronic esters via highly diastereoselective cyclopropanation of the respective alkenyl boronic esters with diazomethane catalyzed by Pd(OAc)2(119]. The enantiomerically pure alkenyl boronic esters were prepared by direct hydroboration of the respective alkynes with the chiral 1,3,2-dioxaboro-lane (144). The ter-butyldimethylsilyl protecting group in the boronic ester could be selectively deprotected and the resulting hydroxymethyl alkenyl boronate was also cyclopropanated to give hydroxymethylcyclopropyl boronic esters with good diastereoselectivity (Scheme 3.78). 

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