Boronic esters rearrangements

S,S)-Diisopropylethanediol and (/ ,/ )-2,3-butanediol are also effective chiral directors in boronic ester rearrangements. Both of these vicinal diols are C symmetric and the butanediolboronic esters are readily hydrolyzed to boronic acids, which can then be reesterified if a change in chiral direction is required. 

As a conseqnence of their superior stability, many types of allylic boronates can be isolated and purified. It should be noted that most pinacol allylic boronic esters and other bnlky esters are stable to hydrolysis and can be conveniently pnrified by chromatography on silica gel. A potential pitfall of all allylic boron componnds is their stereochemical integrity, and snbstituted allylic boranes are known to nndergo reversible borotropic rearrangements at temperatures above —45° (see Eq. 12, M = Eor this reason, allylic boranes are nor-... 

Addition of anhydrous zinc chloride and warming to 20 C causes rearrangement of the borate complex 3 to the x-chloro boronic ester 4. If an (S,5)-diol boronic ester 1 or 2 as illustrated is used, the product is generally — 99 % (a/ )-a-chloro boronic ester 4 based on NMR analyses. The enantiomeric (/ ,/ )-diol boronic ester yields the (aS)-a-ehloro boronic ester4. 

Reaction of an (S, S )-diol (a/ )-0 -chloro boronic ester 4 with a Grignard or lithium reagent leads to an intermediate borale complex30 5 which rearranges to a secondary alkyl boronic ester 6. One use of the secondary alkyl boronic ester 6 is oxidation with alkaline hydrogen peroxide, which is known to proceed with retention of configuration31, to form the corresponding chiral secondary alcohol. 

S)-Pinanediol boronic esters 2 with (dichloromethyl)lithium produce (aS)-a-chloro boronic esters 3. The first experiments provided diastereomerie ratios in the range 75 25 to 98 2. The best results (>94 6) were obtained with phenyl, ethenyl, or 1-phenylethyl attached to the boron atom39 40. The diastereomerie ratios were estimated from the rotations of esters of derived secondary alcohols. It was subsequently found that zinc chloride catalysis of the rearrangement of the intermediate borate complexes 2 improved the yields, usually to 85-95%, with diastereo-meric ratios often >99 1 when R1 = alkyl, as shown by NMR measurements15,43. 

Before preparation of any a-halo boronic ester is undertaken, it should be noted that two sets of model conditions are outlined in what follows. If the group R1 of the boronic ester 1 is a typical alkyl group, then the rearrangement of the derived borate complex 2 requires a number of hours at 20 C, but if R1 is aryl or alkenyl, then shorter times and lower temperatures are required in order to avoid epimerization of the product 3 catalyzed by zinc chloride and lithium... 

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. 

Alkylbromoborancs (1) can also be used to provide frans-alkenes by hydroboration of a 1-bromo- 1-alkyne. The adducts rearrange with sodium methoxide to (trans-l-alkyl-l-alkcnyl)boronate esters (3), which can be converted into either tran.v-alkenes (4)or ketones (5), as shown inequation III.7... 

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... 

Allylic alcohols may be derived from alkenes by metallation to give the allylpotassium species, followed by treatment with fluorodimethoxyborane. Oxidation of the resultant boronic ester with hydrogen peroxide gives the allylic alcohol (Scheme 15). ° - ° Some allylic rearrangement may be observed for example, metallation of a-pinene with potassium r-butoxide in petroleum ether solution and subsequent boration and oxidation gave myrtenol (42%) and /rons-pinocarveol (1%) (equation 24), while treatment of the allylpotassium with oxirane gave the alkylated prc ucts in a ratio of ca. 2 1. ° ... 

When 18 is treated with acetone, boronic ester 20 with a cyclooctatriene structure is cleanly obtained indicating the valence tautomerism between 18 and 19. In fact, 19 appears to be the kinetic product in the borylation of lithium or potassium cyclononatetraenide with alkylboron dihalides which rearranges quickly to 18 due to the comparatively high thermodynamic stability of the latter.1819 Acetaldehyde,... 

Asymmetric Ireland-Claisen Rearrangements. Chiral enolates derived from the boron complex (5) and allyl esters rearrange with excellent selectivity upon warming to —20 °C for a period of 1-2 weeks (eqs 9 and 10). As discussed above, the geometry of the intermediate enolate can be controlled by appropriate choice of base and solvent, thus allowing access to either syn or anti configuration in the product The reaction can be completed in 2-4 days with little erosion in selectivity when run at 4 °C. 

The plant bufadienolide scillarenin (500) has been synthesized. The starting material was 15a-hydroxycortexone (501), which was converted into the diketone ketal (502) by cupric acetate oxidation at C(21), followed by selective ketalization and tosylate elimination. Protection at C(3) as the dienol ether, oxiran formation at C(20) with dimethylsulphonium methylide, and regeneration of the C(3)- and C(21)-oxo-groups by acid hydrolysis then provided (503). Selective reaction at C(21) with the sodium salt of diethyl methoxycarbonyl-methylphosphonate, and boron trifluoride rearrangement of the epoxide ring to the aldehydo-unsaturated ester (504), was followed by enol lactonization to the bufadienolide (505). This was converted, in turn, to scillarenin (500) via the 14,15-bromohydrin, by standard reactions. Unsubstituted bufadienolides have also been prepared by the same method. 

The transfer of the allylic moieties from boron to the electrophilic carbonyl carbon proceeds via rearrangement to form intermediate boronic esters C and D (see below). The reaction is highly diastereoselective. The ( )-crotylboronate reacts to give the anfr-homoallylic alcohol and the (Z)-crotylboronate reacts to afford the syn-homoallylic alcohol.This behavior has been interpreted in terms of the Zimmerman-Traxler chair-type transition state model.Because of the double bond geometry, coordination of the (Ei-crotylboronic ester places the Me preferentially equatorial, whereas coordination of the (Z)-crotylboronic ester places the Me axial, as illustrated in the cyclohexane chair-form transition state conformations A and B, respectively. In both cases, the R moiety of the aldehyde must occupy a pseudo-equatorial position to avoid steric repulsion by one of the OR substituents on boron. 

Boronic esters (8) react with dichloromethyllithium to form intermediate borate complexes which then undergo rearrangement to form 2-haloboronic esters (9). When treated with a Grignard reagent, the 2-haloboronic esters (9) rearrange to secondary alkylboronic esters (10 Scheme 3). 

Boronic esters are not as reactive as triorganylboranes towards nucleophiles however, rearrangement does take place if the boronic ester is treated with an a-halocarbanion (equation 54). In this case, the I-chloroethylboronate (36) can be obtained in 95% de due to the diastereofacial influence of the chiral pinanediol. Similarly, chloro- or bromo-alkylboronic esters react with Grignards reagents, alkyllithiums and enolates leading to rearranged products. ... 

Chiral boronic esters react with organolithium reagents to form diorganylalkoxyboranes (borinic esters). Subsequent reaction with the anion of dichloromethyl methyl ether then yields chiral ketones by rearrangement of both of the groups on boron (Scheme 42). No racemization is observed in this sequence and alkyl-, aryl- or alkynyl-lithium reagents can be used. 

Most [3,3]-sigmatropic rearrangements take place thermally, and the Cope, oxy-Cope and Claisen rearrangements are among the most important rearrangements in this class. Important variants of the Claisen rearrangement include the Johnson modification via orthoesters, the Eschenmoser modification via ketene N,O-acetals, the Ireland modification via ketene silylacetals and the Corey modification via boron ester enolates [696], The aza-Claisen rearrangement has also seen... 

Finally, the etiojervane analogue of corticosterone (236) has been synthesized from jervine (231), through the known intermediate (232). The unsaturated a-hydroxy-ester (233) was prepared from (232) by a Darzens reaction, followed by boron trifluororide rearrangement. Selective catalytic hydrogenation and lithium aluminium hydride reduction gave a tetraol, isolated as its acetonide (234), which by oxidation at C-3 gave the ajS-unsaturated ketone (235). The last steps of the sequence, which involved modifications of the side-chain, entailed acid hydrolysis, acetylation of the primary alcohol, and oxidation at C-20 to give (236)." ... 

Alkene synthesis (4, 37, 110). Evans et al. have developed variations of the Zweifel boron-mediated olefination reaction that lead to improved results. Boronic ester ate complexes (a) and (b) were used for the rearrangement, which... 

Allylic alcohols may be derived from alkenes by metallaticHi to give the allylpotassium species, followed by treatment with fluorodimethoxyborane. Oxidation of the resultant boronic ester with hydrogen peroxide gives the allylic alcohol (Scheme Some allylic rearrangement may be observed for... 

MeOTf has been reported to effect the dealkoxylation of a perfluoroalkyltrialkoxyboronate to generate the corresponding boronic ester, l Conversely, an alkenyl boroxycarbene complex was reacted with MeOTf to remove the borane-based chiral auxiliary yielding a Fischer carbene complex. l l ferf-Amide substituted oxetanes rearranged in anhydrous nitrobenzene at 150 °C with a catalytic amount of MeOTf to produce ester-substituted azetidines (eq 16).i Other acids such as boron trifluoride ether-ate, trifluoromethanesulfonic acid, and benzylthiolanium hexaflu-oroantimonate led to low yields of the desired azetidines. 

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