Boronic esters synthesis

An alternate strategy was utilized in the synthesis of a potential thyroid receptor ligand [30]. Electrophilic bromination was followed by the Miyaura boronic ester synthesis to yield 49 [31]. Suzuki coupling between 49 and 2-bromothiazole was then accomplished to provide 50, a precursor to the derivative 51. Unfortunately, the presence of the thiazole at C(3), in 51 resulted in a decrease in binding affinity and selectivity as compared to the lead compound. 

An alternative synthesis of (Z)-l-halo-l-alkenes involves hydroboration of 1-halo-l-alkynes, followed by protonolysis (246,247). Disubstituted ( )-and (Z)-a1keny1 bromides can be prepared from ( )- and (Z)-a1keny1 boronic esters, respectively, by treatment with bromine followed by base (248). 

Aldehydes aie conveniendy synthetized by the reaction of boronic esters with dichloromethylhthium or (phenylthio)methoxymethylhthium (336,337). The synthesis of medium-ting boracyclane stmctures by stepwise ring enlargement is based on the reaction of B-methoxyboracycles with chloromethylhthium (338). 

Synthesis of OC- and P-Ghiral Ketones, Esters, and Nitriles. Chiral boronic esters are convenient precursors of a-chiral ketones (R COR ), which can be prepared via the dialkylborinic ester or dialkylthexyl route (524,525). 

Boronic esters, RB(OR )2 react with methoxy(phenylthio)methyllithium, LiCH(OMe)SPh, to give salts, which, after treatment with HgCl2, and then H2O2, yield aldehydes.This synthesis has been made enantioseiective, with high ee values (>99%), by the use of an optically pure boronic ester, for example ... 

The protocol offers a direct and efficient method for the synthesis of the boronic ester in the solid phase, which hitherto met with little success using classical methodology (Scheme 1-42). A solid-phase boronate (113 [155], 114 [156]) is quantitatively obtained by treating a polymer-bound iodoarene with the diboron (82). The subsequent coupling with haloarenes furnishes various biaryls. The robot synthesis or the parallel synthesis on the surface of resin is the topic of further accounts of the research. 

Scheme 32 summarizes Matteson s synthesis of serricornin [(4S,6S,7S)-21], the female sex pheromone of the cigarette beetle (Lasioderma serricorne) via boronic esters [55]. Due to the highly stereoselective nature of boronic ester chemistry, this synthesis of 21 was quite efficient. 

Scheme 11.8 Synthesis of the triflate and boronic ester coupling partners...

In 2011, Hartwig and coworkers reported the total synthesis of taiwaniaquinol B (55, Scheme 11.9), a member of a family of diterpenoids that are derived from the abietane skeleton [36]. A key aspect of the Hartwig synthesis of taiwaniaquinol B was the use of the iridium-catalyzed borylation reaction to accomplish the C(5) functionalization of resorcinol derivative 53. This regioselectivity for the overall bromination is complementary to that which would be obtained using a standard electrophilic aromatic substitution (EAS) reaction. In the transformation of 53 to 54, a sterically controlled borylation was first accomplished, which was then followed by treatment of the boronic ester intermediate with cupric bromide to... 

Similarly, we anticipate that boronic ester 52 should prove highly useful for the synthesis of other lycodine-derived Lycopodium alkaloid pseudodimers including complanadines D and E (see Scheme 11.2) as well as unnatural analogues for biological studies. This is the direction of our ongoing research in this area. 

Scheme 11.14 Application of boronic ester 52 to the synthesis of lycopladines F and G...

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. 

Sulfonylhydroxylamines and hydroxylamine O-sulfonic acid have found wide apph-cation in synthesis of amines from achiral or chiral organoboranes and boronate esters and the hydroboration-amination methodology is successfully used for direct amination of alkenes. 0-Sulfonyloximes were also found to be good reagents for synthesis of amines from organomagnesium, -copper and -zinc reagents. 

Addition reactions of allylic boron compounds have proven to be quite general and useful. Several methods for synthesis of allylic boranes and boronate esters have been developed.36 37 The reaction has found some application in the stereoselective synthesis of complex structures. 

Scheme 9.3 illustrates some examples of synthesis of allylic carbinols via allylic boranes and boronate esters. 

The synthesis in Scheme 13.31 also relies on me.so-2,4-dimethylglutaric acid as the starting material. Both the resolved aldehyde employed in Scheme 13.30 and a resolved half-amide were successfully used as intermediates. The configuration at C-2 and C-3 was controlled by addition of a butenylborane to an aldehyde (see Section 9.1.2). The boronate ester was used in enantiomerically pure form so that stereoselectivity was enhanced by double stereodifferentiation. The allylic additions carried out by the butenylboronates do not appear to have been quite as highly stereoselective as the aldol condensations used in Scheme 13.30, because a minor diastereomer was formed in the boronate addition reactions. 

The synthesis by K. C. Nicolaou and co-workers is summarized in Scheme 13.43. Diels-Alder reactions are prominent in forming the early intermediates. The formation of the A ring in steps A and B involves use of z-cli loroacrylonitrile as a ketene synthon. In step C, the pyrone ring serves as diene. This reaction is facilitated by phenylboronic acid, which brings the diene and dienophile together as a boronate ester, permitting an intramolecular reaction. 

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