Triisopropyl borate ester

Racemic l-methyl-2-butenylboronates (E)- and (Z)-3 may be prepared selectively via reactions of the l-methyl-2-butenyl Grignard reagent with the appropriate borate ester. Use of triisopropyl borate provides a 96 4 mixture of (E)-3l(Z)-3 on a 0.36 mol scale15. Use of a bulkier borylating agent, such as 2-isopropyloxy-4,4,5,5-tetramethyl-l,3,2-dioxaborolane, reverses the selectivity, enabling a 91 9 mixture of (Z)-3/( )-3 to be obtained on a 0.5 mol scale. The diastereomeric purity of this mixture may be enhanced to 95 5 by treatment with 0.15 equivalents of benzaldehyde, since ( )-l-mcthyl-2-butenylboronatc ( )-3 is more reactive than (Z)-3. Repetition of this process provides (Z)-3 that is 98% isomerically pure. 

As first described by Krizan and Martin,6 the in situ trapping protocol, i.e., having the base and electrophile present in solution simultaneously, makes it possible to lithiate substrates that are not applicable in classical ortho-lithiation reactions.7 Later, Caron and Hawkins utilized the compatibility of lithium diisopropylamide and triisopropyl borate to synthesize arylboronic acid derivatives of bulky, electron deficient neopentyl benzoic acid esters.8 As this preparation illustrates, the use of lithium tetramethylpiperidide instead of lithium diisopropylamide broadens the scope of the reaction, and makes it possible to functionalize a simple alkyl benzoate.2... 

Finally, compound (iv) is condensed with either trimethyl(6-methyl-3-pyridyl)tin or the boronate ester by means of Pd(PPh3)4 to afford etoricoxib. The metallated pyridine (vii) is obtained by esterification of 3-hydroxy-2-methylpyridine with triflic anhydride to give the corresponding triflate, which is treated with a tin reagent to yield the target tin intermediate. The boron lithium salt (viii) is prepared by treatment of 5-bromo-2-methylpyridine with butyllithium followed by addition of triisopropyl borate. 

An alternate synthesis is outlined in Scheme 2.1 2 Diisopropyl dichloromethylboronate (6) is readily prepared by reacting triisopropyl borate with dichloromethyllithium prepared in situ. 20 Transesterification with a suitable C2 symmetric diol gives an ester 7 that can be treated with an alkylmagnesium bromide to yield chloride 8 and then, after transesterification with pinanediol (see Section 15.1.7.2) a product 9 which is analogous to 3. 

SYNS BORIC ACID, TRIISOPROPYL ESTER TRIISOPROPYL BORATE (DOT)... 

However, the application of these classical procedures for 1-alkenylboronic acid or ester synthesis may suffer from the formation of small amounts of the opposite stereoisomers, or from bis-alkenylation leading to the boronic acid derivatives. Also, formation of trialkylboranes may occur. A recent useful variant utilizes organolithium reagents and triisopropyl borate, followed by acidification with HCl to give directly alkyl-, aryl-, 1-alkynyl-, and 1-alkenylboronic esters in high yields, often over 90% (Scheme 2-6) [27]. Triisopropyl borate was shown to be the best of the available alkyl borates to avoid multiple alkylation of the borates. 

The transmetallation of (R 0)3B with R—M (M=Li, MgX) at low temperature (usually at -78 C) proceeds by initial formation of a relatively unstable teracoordinat-ed complex [RB(OR0i]M, which is in equilibrium with RB(OR )2 and R OM. If the monoalkyl(trialkoxy)borate can be cleanly formed, and if equilibrium favors this complex, the boronic ester will be formed selectively. Otherwise, successive steps will give rise to the di-, tri-, or tetraalkylborates (eq (7)). Triisopropyl borate is shown to be the best of the available alkyl borates to prevent such side reactions thus allowing the syntheses of a number of alkyl, aryl. 1-alkenyl [9]. and 1-alkynylboronates [10] in high yields, often over 90% (eq (8)). 

A variety of alkyl- and arylboronic acids can be obtained in large quantity by the above general procedure. The reaction of organolithiums with triisopropyl borates at -78 °C is an alternative and convenient method to achieve high yields of boronic acids or their esters [9, 10] (eq (8)). 

Almost 40 years after the Lilly procedure was disclosed, a crystalline borate ester was prepared by an analogous method. Dissolution of 3-bromopyridine and triisopropyl borate in toluene-THF followed by the addition of n-BuLi in hexanes at 0°C delivered the borate ester in good yield (Scheme... 

Boric acid, octyidodecyl triester. See Trioctyidodecyl borate Boric acid, sodium salt. See Sodium metaborate Sodium perborate Boric acid, tributyl ester. See Tributyl borate Boric acid, triisopropyl ester. See Triisopropyl borate... 

The use of triisopropyl borate is the most popular nowadays since it generally allows to carry out the reactions at common reaction temperatures, between -25 and 0 °C. The acid catalysed hydrolysis of the arylboronic esters is affected by adding dilute aqueous hydrochloric, acetic acid or even water, at 0 to room temperature, to the reaction mixture containing the crade arylboronic ester, to produce the corresponding... 

Simple (halomediyl)boronic esters are not accessible by methods used for higher homologs. The discovery that (chloromethyl)lithium can be generated at -78 C from chloroiodomethane by treatment widi butyllithium in the presence of triisopropyl borate and captured immediately to form the (chloromethyl)borate salt and, after acidification, the boronic ester has provided practical access to these useful reagents [33]. The less expensive reagent dibromomethane under similar conditions generates (bromomethyl)lithium and yields (bromomethyl)(triisopropyl)borate anion (42), which is converted into diisopropyl (bromomethyl)boronate (43) by treatment with anhydrous hydrogen chloride or, more conveniently, methanesulfonic acid while the reaction mixture is still cold (Scheme 8.8) [34]. 

In the aromatic and heterocyclic series, no hydroboration is possible. In general, an organoalkali intermediate is prepared by metalation or halogen/metal permutation before being treated with a boric acid derivative such as trimethyl borate or, because of its cleaner reaction, triisopropyl borate. The resulting ate complex sets free the oxidizable boronate upon addition of water or a stoichiometric amount of diluted hydrochloric acid. The boronate can be accessed directly when fluorodimethoxyborane is used instead of a boric acid ester as the adduct eliminates lithium fluoride spontaneously. The oxidation relies on the same procedures and principles as outlined above. 

Synonyms Boric acid, triisopropyl ester Boric acid, tris (1-methylethyl) ester Boron isopropoxide Boron triisopropoxide Isopropyl borate... 

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