Boronate intermediates

The mechanism of these alkylations involves a tetracoordinate boron intermediate formed by addition of the enolate of the a-bromo ester to the organoborane. The migration then occurs with displacement of bromide ion. In agreement with this mechanism, retention of configuration of the migrating group is observed.23... 

Several methods for stereoselective alkene synthesis are based on boron intermediates. One approach involves alkenylboranes, which can be prepared from terminal alkynes. Procedures have been developed for the synthesis of both Z- and E-alkenes. 

Boron intermediate standard solution, 20 pg B mM - Pipette 20 ml of the boron stock standard solution into a 100 ml volumetric flask and make up to the mark with water and mix. 

Conversion of the 6-bromoquinazolinone 177 to the 6-hydtoxy derivative 178 has been achieved through the oxidation of a boron intermediate <2004HCA1333>. 

This sequence does not use the Matteson boronate intermediate however, was referenced as the method for the conversion. 

Step c Diethanolamine is added to sequester boron from the boron intermediates. 

We anticipated that Johnson et al. would file in the PCT countries within the permitted one year period expiring September 16, 1993. We needed to see what Johnson et al. would claim in Europe. In Europe, in contrast to the United States, the patent prosecution file is open to public inspection. It was thus possible to find out that Johnson et al. had indeed filed a corresponding patent application8 in Europe and to see what patent claims they were pursuing. We found that the claims being pursued were essentially the same as those in the United States. Thus, only the claims to boron intermediates were a potential impediment to our planned European manufacture. Could Johnson et al. obtain valid claims to such intermediates ... 

In considering this question, we noted the following. It seemed to us that Choi, in his earlier 1991 disclosure of the lithium borohydride reduction of diethyl 2-phenylmalonate, may well have produced boron intermediates falling within the Johnson et al. intermediate patent claims. If this were so, then the Johnson et al. patent claims to boron intermediates would be invalid if they were the same as the boron intermediates previously produced by Choi. In short, the Johnson et al. claims would be open to attack as lacking novelty. We investigated. We undertook a boron NMR analysis of the following fully reduced solutions ... 

All three solutions showed the presence (NMR) of the same boron intermediates. In light of this evidence, it was clear that Johnson et al. could not obtain a grant in Europe of valid patent claims to boron intermediates that would be an impediment to us. (Incidentally, for the same reason, Schering could not obtain such intermediate claims.) On the other hand, the Johnson et al. methyl tropate reduction process was patentable over the disclosed Choi diethyl phenylmalonate reduction process and Schering s formyl phenylacetate process was patentable over both the disclosed Choi and Johnson et al. processes. Both were novel and both had a basis for showing nonobviousness. 

Finally, as shown by Kabalka and Yao [131] bis(pinacolato)diboron can be applied in a sequential Pd-catalyzed Miyaura borylation and Suzuki coupling to a (bromomethylene)cyclobutane furnishing an efficient synthesis of the (dicyclobutylidene)-ethane derivative 184, whereas the presumed boronate intermediate 185 was only obtained in trace amounts (Scheme 72). 

S.M.A. Elgendy etal, US Patent 5,596,123 (January 21, 1997) Assignee Thrombosis Research Institute Utility Chiral Boron Intermediates... 

Stereoselective reduction of a y-hydroxy ketone. Reaction of the y-liydroxy ketone 1 with LiAIHj. ZnBHi. or NaBHj yields about equal amounts of the two possible diols. However, reduction 4 ith Li(C,H,),BH (2 cquiv.) yields only one product (2) in yield. The high stereoi-icicctivity is attributed to formation of a chelated boron intermediate that favors attack by the hydride from the (3-facc. The diol (2) is converted by TsCI into ancistrofuran (3), a ddfensive secretion of certain termites. 

Reaction of the organoborane R- BY2 with "OH forms a nucleophilic boron intermediate that transfers an alkyl group from boron to palladium in Step [3]. 

The latter method has also been applied to one substrate with an equatorial hydroxy group at C-3, i.e., /ra .s-4-/err-butyl-3-hydroxycyclohexanone43. It was rather less successful, probably because intramolecular hydride delivery has to occur through a boat conformation of the boronated intermediate, and this is sufficiently slow to allow some intermolecular reaction. The use of acetone/acetic acid as solvent improved the selectivity, presumably by suppressing the intermolecular reaction, although this resulted in a rather low yield. 

Cationic tricoordinate boron intermediates, including N-heterocychc carbenes as stabilizing Hgands for borenium salts 12CRV4246. 

The use of milder base potassium 2,6-di-f-butoxide to alkylate ethylbromo-acetate in THE results in the drop of yield to 0%. This is reasoned owing to the slow protonolysis of the rearranged boron intermediate, so that it is capable of reacting competitively with freshly formed a-bromo carbanion. 

---