Alkoxy-substituted Boronic Esters

Although B-0 bonds are much stronger than B-C bonds and thermodynamics favors boron-oxygen elimination from B-C-C-0 linkages to form B-0 + C=C, such elimination from (P-alkoxyalkyl)boronic esters is not normally observed unless the compounds are heated above 50-60 °C. This kinetic stability has allowed the synthesis of a wide variety of alkoxy substituted boronic esters. Synthetic targets are usually hydroxy compounds, for which benzyloxy, (p-methoxybenzyl)oxy, and trityloxy groups are useful precursors. 

Schenie8.11 Preparation of (S)-pinanediol (R)-[l -(benzyloxy)penty(]boronate. 

The roundabout route to 57 via 56 was required because attempted direct replacement of a-halide by hydroxide or (trimethylsilyl) oxide had failed in a model compound. In view of the instability of (a-aminoalkyl)boronic esters toward deborona-tion, described in a subsequent section, it is plausible that an (a-hydroxyalkyl)boronic ester might deboronate similarly if the hydroxyl group was deprotonated by base, though (a-hydroxyalkyl)boronic ester 57 and related compounds are stable under neutral or acidic conditions. (Trimethylsilyl)oxide apparently failed because the pinanediol oxygens migrated faster than the silyloxide from boron to carbon [41]. 

Methylation of 70 provided 72, which contains all of the remaining carbon atoms of 79. Dichromate oxidation of the secondary alcohol from debenzylation of 72 resulted in low yields and partial oxidation of the DICHED. Hydrolysis of 72 to the cyclic borate 73 proved feasible, and oxidation yielded ketone 74 (-35% yield from 69). 

Conversion of 74 into a boron enolate 75 and aldol condensation with 71 to form postulated intermediate 76 was followed by appropriate steps to yield 77, the first intermediate that was normally purified by chromatography in the sequence. Debenzyla-tion resulted in the first crystalline sample of stegobiol (78), a minor component of the natural pheromone. However, tests of pure 78 by Wendell Burkholder showed no attractant activity [48], in contrast to the low activity previously reported for oily natural samples. Perruthenate-catalyzed oxidation of 78 with N-methylmorpholine N-ox-ide yielded pure crystalline stegobinone (79) having very high attractant activity. 

---

In addition to trialkylboranes, various alkoxyboron compounds have prominent roles in synthesis. Some of these, such as catecholboranes (see. p. 340) can be made by hydroboration. Others are made by organometallic or related substitution reactions. Alkoxyboron compounds are usually named as esters. Compounds with one alkoxy group are esters of borinic acids and are called borinates. Compounds with two alkoxy groups are called boronates. Trialkoxyboron compounds are borates. 

Syntheses of simple diols are described first, followed by a multistep synthesis of ribose. These syntheses illustrate the compatibility of alkoxy substituents on boronic esters with their reaction with (dihalomethyl)lithium. The limitations of this compatibility, as well as failure of a (chloro-allyl)boronic ester to undergo substitution by alkoxides, are also noted. Retention of configuration of the migrating group is a consistent and repeated feature of these syntheses. 

Benzoxathiolium salts have proven to be effective masked acylating agents (79S223). 2-Substituted 1,3-benzoxathiolium tetrafluoroborates have now been utilized in the preparation of esters. Reaction of the salt (334) with two equivalents of an alcohol gave the 2-alkoxy-2-alkyl-benzoxathiole (335). Hydrolysis of (335) with red mercury(II) oxide and boron trifluoride etherate in aqueous THF delivered ethyl benzoate in excellent yield (Scheme 72). 

---