Allylboronates preparation

Allylboronates prepared from simple diols display appreciable reactivity, but eyelie boronate derivatives prepared from 1,2- or 1,3-diols display considerably less. The commonly employed pinacol esters are among the least reactive members of this class. 2-Allyl-3-methyl-l,3,2-oxaza-... 

If R1 differs from R2. the preparation may lead to both regioisomers. In these cases, a synthetic route which does not rely on allyl anion substitution is often the most advantageous one. Thus, the best results are recorded for allylboronates and -silanes which also possess the required constitutional and configurational stability. 

A large number of publications appeared on these aspects5, but most of these studies did not address stereochemical questions. In most cases, a given synthetic problem can be better solved by other allylmetals. Grignard reagents have some importance as intermediates for the preparation of allylboronates (Section D.1.3.3.3.3.2.1.), allylsilanes (Section D.1.3.3.3.5.2.L), allyl-stannanes (Section D. 1.3.3.3.6.2.1.1.), or allyltitanium derivatives (Section D.I.3.3.3.8.2.). 

L Preparation of Allylboranes and Allylboronates Lacking Stereogenic Centers... 

One of the most general preparative routes to allyl- and 2-butenylboranes involves the reaction of an allylic organometallic species and an electrophilic borylating reagent. Various esters of allylboronic acid have been prepared in this way2,4-5. 

Recent optimization studies reveal that the yield of 2-(2-propenyl)-1,3,2-dioxaborolane-4,5-di-carboxylate esters (i.e., the tartrate ester modified allylboronates) is improved by using triiso-propyl borate as the borylating agent1. The improved yields are directly related to the increased efficiency of the preparation of the intermediate allylboronic acid. 

Alkylthio-substituted allylboronates have also been prepared27. The ethylthio -isomer, however, was prepared with only 70% isomeric purity. 

A second powerful route to functionalized allylboron compounds involves the reaction of an a-haloalkylboronatc and a vinyl organometallic reagent3 4-28-29, 50c-92 04. This method is especially useful for the preparation of allylboron compounds not accessible via the allylorganometal-lic route. Notable examples that fall into this category are ( )-4,4,5,5-tctramethyl-2-[4-(tetrahy-dro-2//-pyran-2-yloxy)-2-butenyl]-l,3,2-dioxaborolane (yield 41 %, 93% E) and (E)- or (Z)-2-(l,l-dimethyl-2-butenyl)-4,4,5,5-tetramethyl-1.3,2-dioxaborolane (yield 77-84%. 98% E or 93% Z). 

A potentially useful route to substituted (Z)-allylboron derivatives involves the selective cis hydrogenation of propynylboron derivatives. One recent report applied this approach in the synthesis of a (Z)-3-trimethylsilyl-2-propenylboronate, which cannot be prepared by the allyl-organometallic route discussed in Section 1.3.3.3.3.1.1.1. The selectivity for the Z-isomer was only 9 1 21. The scope of this method remains to be fully documented35. 

In contrast to the 2-butenylboranes, 2-butcnylboronates have found widespread application in acyclic diastereoselective synthesis owing to their ease of preparation (Section 1.3.3.3.3.1.1.), configurational stability and highly stereoselective reactions with aldehydes3 4. The results of reactions of substituted allylboronates and representative achiral aldehydes are summarized in Table 1. 

The tartrate ester modified allylboronates, the diisopropyl 2-allyl-l,3,2-dioxaborolane-4,5-di-carboxylates, are attractive reagents for organic synthesis owing to their ease of preparation and stability to storage71. In the best cases these reagents are about as enantioselective as the allyl(diisopinocampheyl)boranes (82-88% ee with unhindered aliphatic aldehydes), but with hindered aliphatic, aromatic, a,/l-unsaturated and many a- and /5-alkoxy-substituted aldehydes the enantioselectivity falls to 55-75% ee71a-b... 

Several applications of this methodology to the synthesis of racemic a-substituted allylboronates are provided in refs 2-4. It is noted that reagents 6 (X = Br) and 7 are unstable with respect to ailyl rearrangement of the halide ions, either thermally or in tile presence of halide ion, and so care must be exercised in the preparation and handling of a-haloallvlboronates. 

An extremely attractive feature of the route outlined at the beginning of this section for the transformation of boronates 3 or 4 to a-substituted allylboron compounds 5 is that reagents with very high enantiomeric purity (> 90% ee) may be prepared when precursors such as 3 and 4, and therefore also ate complex 1, contain a suitable diol chiral auxiliary17. The following syntheses of (S)-68, lib9, and 1310 illustrate this feature. 

Chiral, nonracemic allylboron reagents 1-7 with stereocenters at Cl of the allyl or 2-butenyl unit have been described. Although these optically active a-substituted allylboron reagents are generally less convenient to synthesize than those with conventional auxiliaries (Section 1.3.3.3.3.1.4.), this disadvantage is compensated for by the fact that their reactions with aldehydes often occur with almost 100% asymmetric induction. Thus, the enantiomeric purity as well as the ease of preparation of these chiral a-substituted allylboron reagents are important variables that determine their utility in enantioselective allylboration reactions with achiral aldehydes, and in double asymmetric reactions with chiral aldehydes (Section 1.3.3.3.3.2.4.). 

The matched double asymmetric reactions with (7 )-l and (a.R,S,S)-2 provide the (S,Z)-diastereomer with 94% and 96% selectivity, while in the mismatched reactions [(S)-l and (aS,R,R)-2] the (S.Z)-diastereomer is obtained with 77% and 92% selectivity, respectively. Interestingly, the selectivity of the reactions of (/ )-2,3-[isopropylidenebis(oxy)]propanal and 2 is comparable to that obtained in reactions of (7 )-2,3-[isopropylidenebis(oxy)]propanal and the much more easily prepared tartrate ester modified allylboronates (see Table 7 in Section 1.3.3.3.3.1.5.)41. However, 2 significantly outperforms the tartrate ester allylboronates in reactions with (5)-2-benzyloxypropanal (Section 1.3.3.3.3.1.5.), but not the chiral reagents developed by Brown and Corey42-43. 

The possible bis-l-boraadamantane structures are presented in Figure 8. However, the structures 62, 63, and 7 (n = 0) seem to be highly strained and therefore the compounds cannot be prepared via allylboron-acetylene condensation. At least one CH2 bridge between the 1-boraadamantane cores 7 (n> 1) is needed to stabilize the molecule . 

A double set of signals in the 13C NMR spectra of THF and pyridine complexes of bridged bis-l-boraadamantanes initially prepared via an allylboron-acetylene condensation-hydroboration sequence shows that these compounds consist of a mixture of racemic and meso-imms <1998IZV728, 2000IZV501, B-2003MI94>. THF complexes show nB NMR shifts at about 12 ppm, whereas the pyridine analogues resonate at about —3 ppm (Table 4). 

Lallemand et al. have found a pericyclic-anionic domino three-component reaction to prepare highly functionalized alcohols.115931 This reaction was originally developed by Vaultier, Hoffmann et al.[59bl Diels-Alder reaction of a 1,3-dienylboronate with an acrylate yields a mixture of endo and exo diastereomers of the coupled allylboronate, which in the presence of an aldehyde such as 4-phenoxy-butyraldehyde undergoes an allylation reaction. After hydrolysis the resulting diastereomeric alcohols are obtained in about 50 % yield, whereby two new stereogenic centers are formed in a stereoselective fashion. 

The allyl boronate esters (R,R)- and (S,S)-1 are prepared by reaction of allylboronic acid, CH2=CHCH2B(OH)2 with l- and D-diisopropyl tartrate.1... 

Aldehyde 13, readily prepared by a four step synthesis from L-threonine,3a-i5 was treated with the known (Z)-7-methoxyallylboronate 1412a,c. This reaction, as with other reactions of pinacol allylboronates, was relatively slow and required 24-48 h at room temperature to reach completion. It was, however, extremely selective ana provided homoallyl alcohol 15 in 70% yield with greater than 95% diastereoselectivity. The stereochemistiy of this compound was quickly verified by conversion to 3 as shown in Figure 7.3a We now believe that this reaction proceeds by way of the Conforth-like transition state depicted in Figure 7, and not by way of a Felkin transition state as suggested in our original ublication, since a serious nonbonded interaction exists between the (Z)-methoxyl group and the C(3) substituents of 13 in the Felkin transition state. A... 

Figure 8. Preparation of homoallyl alcohol 15 via in situ generated allylboronate 17.

In spite of the poor diastereoselectivity realized in reactions with most chiral aldehydes, allylboronates are highly attractive reagents for organic synthesis.. i. 2,17 i ost are easily prepared in large quantities, and are convenient to use. 8 They are nonbasic, relatively non-nucieophilic, and hence are highly chemoselective in their reactions. 

To access anti-l,2-diols, indirect methods are required for the preparation of geometrically pure, chiral E-3-alkoxy reagents. To this end, the isomerization of alkenylboronic esters described above (Eq. 41), provides a reliable route to tartrate-derived E-3-siloxy allylboronate 99 (Fig. 7). The latter shows variable enantioselectivities in additions to aldehydes, with cyclohexanecarboxaldehyde affording the highest selectivity (Eq. 70). ... 

In the second approach, allylboronation of 9 with 10 led to the predominant formation of 8a which was transformed to 6a (R = H). The allylic alcohols 5a and 5b prepared from 6a and 6b, respectively, were subjected to asymmetric epoxidations307, each with (-f)-DET and (—)-DET, to provide four diastereomers. One of them, 4b, was identical with degradation product 2. Note that in these reactions double stereodifferenlialion (see Section A.2.3.5.4.) is operating (for configurational assignment at C-15, see p431)244. 

The rearrangement process depicted in Figure B5.1 involves interaction of the vacant p orbital on boron with the alkene. The presence of n-donor substituents on boron such as -OR or -NR2 reduces the electron deficiency on boron and suppresses the rearrangement. Thus allylboron derivatives with two oxygen substituents, for example, are stable at room temperature and their ( )- and (Z)-isomers can be prepared isomerically pure (see below). 

The reaction tolerated various functional groups, thus allowing the in situ preparation of allylboron compounds possessing a carbonyl group (Equation (32)).236 The tandem diboration-intramolecular allylboration provided a diastereoselective access to the cycloalkanes bearing 1,3-diols. 

The (3-ketoacids and B-allyldiisopropoxyborane were prepared according to published procedures.910 In a typical experiment, the allylboronate (3 mmol in 20 mL of ether) is added... 

These 1,3-budienyl-l-boronic esters are of particular interest since their Diels-Alder cycloaddition leads to allylboronates with a fixed Z configuration, their double bond which is part of the cyclohexenyl moiety. One possible preparation of these compounds is the... 

Allylboron-capped compounds were prepared similarly in rebutanol using triallylborane BAllyla instead of HdB(OH)2. Under these reaction conditions, two of the three B-C bonds in BAllyla are cleaved by re-butanol or water to form AllylB(OH)2 and propane [67]. 

The biologically important 2-deoxypentoses can be prepared readily by the two-carbon chain elongation of 2,3- -isopropylidene-D-glyceraldehyde following Roush s allylation method (Scheme 13.54), relying on the highly diastereoselective additions of enantiomerically pure allylboronates derived from (R,R) and (5, 5 )-tartaric acid [100]. Similarly, the 2,6-dideoxyhexose derivative 155 was obtained by Roush and Straub (Scheme 13.54) [101]. 

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