Boronic ester homologation

Reaction of boronic esters, RB(OR )2, with dichloromethyllithium, LiCHCl2, inserts the CHC1 unit into the carbon-boron bond of the boronic ester. This is known as boronic ester homologation. If boronic esters derived from homochiral alcohols are used in this reaction, then new homochiral centres may be generated as will be illustrated below. 

Many boronic ester homologation reactions have been performed using pinanediols as chiral auxiliaries. These are readily available from (+)- and (-)-a-pinene by osmium tetroxide-catalyzed oxidation reactions (Equations B6.1 and B6.2). 

Boronic ester homologation has been used to synthesize specifically deuterated phenylalanine by the pathway shown in Figure B6.3. 

Recently, Matteson and his co-workers have demonstrated interesting boronic ester homologation with very high chiral selectivity and its use in syntheses of natural products 220 . 

Boronic ester homologation. (R,R)-2,3-Butanediol- and (-(- )-pinanediol have been used as the chiral adjuncts in a diastereoselective homologation of dichloromethaneboronic esters (1) to the (aS)-a-chloroboronic esters (2). Reaction of 1 with an alkyllithium produces a borate complex (a), which rearranges diastereoselectively in the presence of ZnCl, to 2 with introduction of a chiral center adjacent to boron. The reaction permits... 

An important feature of the boron ester homologation reaction is that the boronic ester product E can itself be used as a starting boronic ester so that the cycle can be repeated to introduce a second chiral center. Matteson has used this methodology to synthesize insect pheromones and sugars. 

The conversion of chiral boronic esters iato optically pure B-aIkyl-9-BBN derivatives followed by reaction with a-bromoketones, a-bromoesters, or a-bromonitriles leads to the homologated P-chiral ketones, esters, and nitriles, respectively (526). 

Diastereoselective homologation of chiral alkylboronates (cf. 12, 80-81). Investigations of this reaction have been carried out mainly on boronic esters (1)... 

Homologation, of boronic esters, 23 671 Homologous enzyme structures, 10 337 Homologous promoters, 22 453 Homologous recombination, 22 459-460 Homologous temperature, 23 487 Homology, of proteins, 20 833-834... 

An efficient process for one-carbon homologation to aldehydes is based on cyclic boronate esters.17 These can be prepared by hydroboration of an alkene with dibromobor-ane, followed by conversion of the dibromoborane to the cyclic ester. The homologation step is carried out by addition of methoxy(phenylthio)methyllithium to the boronate ester. The migration step is induced by mercuric ion. Use of enantioenriched boranes and boronates leads to products containing the groups of retained configuration.18... 

Chloromethyl)lithium, generated by addition of butyllithium to chloroiodomethane in the presence of a boronic ester, is efficiently captured to form a (chloromethyl)borate, which rearranges to the homologous boronic ester with full retention of the configuration of the stereocenter as shown by oxidation to a known alcohol48. For a related synthesis of (chloromethyl)boronic esters, see Section 1.1.2.1.3.2. 

For both 1 and 2, the synthesis started with the alkenyl amide 3. Salen-mediated conjugate addition proceeded with remarkable induction, to give S in 92% as a mixture of diastereomers. Reduction and cyclization followed by deprotonation and kinetic quench delivered the enantiomerically-enriched cis dialkyl piperidine 6. Homologation of the two sidechains then gave the alkenyl boronic ester 8. 

Homologation of boronic esters. The reagent 1 can be formed in situ by reaction of CH2C12 with lithium 2,2, 6,6 -tetramethylpiperidide (LiTMP) or even LDA. The product obtained on reaction of 1 with alkylboronic esters, an a-chlo-roboronic ester, is reduced by potassium triisopropoxyborohydride (KIPBH) to the homologated boronic ester.1... 

Chloromethylation of 2-alkyl-1,3,2-dioxaborinancs with dichloromethyllithium followed by reduction with potassium triisopropoxyborohydride yields one-carbon-homologated boronic esters. The homologation can be repeated and the homologated esters transformed into the corresponding at-, j7- or -/-chiral alcohols, aldehydes and acids13. 

This homologation method with chiral boronic esters has wide application and its synthetic potential has been reviewed16. 

Both Brown and Matteson have made substantial contributions concerning the one-carbon homologation of boronic esters e.g (146) using either LiCf Cl or LiCHC - Both research groups have now reported additional progress in the area and new procedures have been... 

Cyclomethylenation of ketones The combination of CH Ij with MeLi LiBr generates iodomethyllithium, which converts carbonyl compounds into epoxides (4 examples, 88-90%). The reagent is also used for the one-carbon homologation of a boronic ester. 

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