Cyclopropylboron

In addition, if this reaction was run in the presence of trimethylborate, a usual zinc-boron exchange led to the cyclopropylboron derivative that could be used in Suzuki coupling to give rise to trisubstituted cyclopropanes (equation 64) . 

A very useful class of chiral auxiliaries has been developed for alkenes substituted with a heteroatom. These auxiliaries, attached to the heteroatom, allow for the preparation of enantiomerically enriched cyclopropanols, cyclopropylamines and cyclopropylboronic acids. Tai and coworkers have developed a method to efficiently generate substituted cyclopropanol derivatives using the cyclopropanation of a chiral enol ether (equation 78) . The reaction proceeds with very high diastereocontrol with five- to eight-membered ring sizes as well as with acyclic enol ethers. The potential problem with the latter is the control of the double bond geometry upon enol ether formation. A detailed mechanistic study involving two zinc centers in the transition structure has been reported. ... 

Chen, H. Deng, M.-Z. A novel Suzuki-type cross-coupling reaction of cyclopropylboronic esters with benzyl bromides./. Chem. Soc. Perkin Trans. 1 2000, 1609-1613. 

As before, nonsymmetric couplings could also be realized from boronic acids, but using a palladium catalyst instead of chromium(II) chloride. Silver oxide was used as an activator for the Pd-catalyzed coupling of cyclopropylboronic acids to allyl bromides (Scheme 10.6).20... 

The synthesis of medicinally relevant 4-substituted 2(5//)-furanones has been achieved by a coupling reaction of the triflate derived from p-tetronic acid with alkyl-and cyclopropylboronic acids (Scheme 10.8).22 This reaction was mediated by bis(acetonitrile)dichloropalladium and silver oxide. Interestingly, optically active cyclopropyl boronic acids were not racemized during this coupling reaction. 

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... 

Scheme 23. Cross-coupling reaction of cyclopropylboronic acids...

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. 

For cyclopropylboron compounds, the initial search for 7r-donation from cyclopropyl to boron using H, and FNMR as well as UV spectroscopy did not provide any evidence for a preference for a bisected conformation for the cyclopropyl. Furthermore, tricyclopropylboron was a stronger Lewis acid than triisopropylboron in the formation of complexes with amines and phosphines . This latter behavior would be favored not only on steric grounds due to the presumed smaller size of cyclopropyl but also due to flT-withdrawal by cyclopropyl, but Ti-donor effects of cyclopropyl would decrease the Lewis basicity. 

Interesting compounds, such as cyclopropylboronic acids and esters which are otherwise not easily accessible due to the apparent lack of convenient and versatile syntheses, can now be prepared by simple cyclopropanation with diazomethane. The carbene transfer to substituted and functionalized alkenes also takes place smoothly in the presence of palladium(II) acetate. Several 1-alkenylboronic acid esters 9 were converted to cyclopropylboronic acid esters 10 using this method. ... 

Pietruszka, J., and With A., Enantiomerically pure cyclopropylboronic esters. Auxiliary- versus substrate-control, J. Chem. Soc., Perkin Trans. 1, 4293, 2000. 

An analogous reaction using alkenyl boronic acids is one of the best processes for the A-alkenylation of pyridones and amides. Indoles can be A -cyclopropylated using cyclopropylboronic acid/cupric acetate. 

Aryl sulfones are synthesized from RS02Na and Ar B(OH)2 under oxidative conditions (DMSO, O2). Two similar procedures, both using Cu(OAc)2 as catalyst but different A-heterocycle addends, have been established. A-Cyclopropylation of indole is accompUshed, also by following a similar recipe, with the necessary changing the coupling partner to cyclopropylboronic acid. CycUzation of A-arylamidines to afford benzimidazoles involves activation of the o-C—H bond in a process realized by the action of Cu(OAc)2 in DMSO (containing 2.5 equiv. HOAc) under O2 at 100°. ... 

Cyclopropanes. Coupling of cyclopropylboronic acids with various activated halides, for example, benzylic, allylic, and acyl halides, leads to substituted cyclopropanes. 

Suzuki coupling. Unsymmetrical ambient temperature in A.A-dimeth Arylcyclopropanes are most amenable to 2 availability of cyclopropylboronic acids a... 

Suzuki coupling. Unsymmetrical biaryls are prepared by Suzuki coupling at ambient temperature in iV,lV-dimethylacetamide in the presence of TIOH. Arylcyclopropanes are most amenable to assembly by a Suzuki coupling, due to the ready availability of cyclopropylboronic acids and esters. 

Halopyridines or pyridinyl triflates take part in palladium-catalysed reactions -Heck, carbonylation, and coupling reactions, for example with alkynes, or in Suzuki reactions with arylboronic acids,and cyclopropylboronic acids. 

Coupling of chiral cyclopropylboronic acid 130 with benzoyl chloride catalyzed by PdCl2(dppf) was achieved by the combination of AgjO and K2CO3 as bases to provide the cyclopropyl phenyl ketone 131 with 92% ee in 77 % yield [56]. 

Pietruska and coworkers reported asymmetric cyclopropanation of chiral B-vinyl-l,3,2-dioxaborolanes with diazomethane in the presence of Pd catalyst 58) (Figure 14). The cyclopropylboronates were utilized for subsequent reactions, such as Suzuki coupling, Matteson homologation, etc. 

Alkenylboronic acids and esters are also very useful substrates (Equation 71, Figure 1.38) [405], in particular to access substituted olefins and dienyl moieties commonly encountered in several classes of bioactive natural products [282, 406]. To this end, Kishi and co-workers examined the influence of the base, and developed an optimal variant using thallium hydroxide [281]. Recently, allylic alcohols were found to couple directly with alkyl and alkenyl boronic acids without the aid of a base [407]. In rare cases, the Suzuki reaction has been applied to the use of alkylboronic acids [296, 408], including cyclopropylboronic acids [409]. Hitherto notorious for their tendency to undergo [3-hydride elimination, alkyl bromides are now suitable as electrophiles under carefully optimized conditions that even allow Csp -Csp couplings with alkylboronic acids (Equation 72) [410]. The Suzuki reaction has also been applied very successfully in solid-phase chemistry and combinatorial library synthesis [411]. It has been applied industrially [412], especially in medicinal chemistry, e.g. in the production of the antihypertensive drug losartan [195]. 

Scheme9.16 Asymmetric synthesis of cyclopropylboronates using a chiral director on the boron atom.

Further transformations of cyclopropylboronates by creation of a new carbon-carbon or carbon-oxygen bond have been largely developed, as well as the modification of the side-chain in the presence of the boronic ester functionality [46]. 

Scheme 23 Copper(I)-catalyzed enantioselective formation of trans- and cis-cyclopropylboronates by Sawamura and Ito...

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