Aldehyde reaction with allylboronate

Allylboron compounds have proven to be an exceedingly useful class of allylmetal reagents for the stereoselective synthesis of homoallylic alcohols via reactions with carbonyl compounds, especially aldehydes1. The reactions of allylboron compounds and aldehydes proceed by way of cyclic transition states with predictable transmission of olefinic stereochemistry to anti (from L-alkene precursors) or syn (from Z-alkene precursors) relationships about the newly formed carbon-carbon bond. This stereochemical feature, classified as simple diastereoselection, is general for Type I allylorganometallicslb. 

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. 

Several examples of reactions of allylboronates and /f-alkoxy-x-unsubstituted aldehydes ha ve been reported63-64. These reactions do not proceed with exceptional selectivity, however, since the stereocenter of the aldehydic component is remote from the site of the developing C-C bond. 

Many of the chiral allylboron reagents discussed in Section 1.3.3.3.3.1.4. have been utilized in double asymmetric reactions with chiral aldehydes. Chiral 2-(2-butenyl)-3.5-dioxa-4-boratri-cyclo[5.2.1.02-6]decanes were among the first chiral reagents of any type to be used in double asymmetric reactions52a,b. 

These reagents are not isolated but are used directly in reactions with aldehydes, after generation of ate complexes via the addition of an alkyllithium reagent or pyridine11. 2-(2-Propenyl)-1,3,2-dioxaborolane is also metalated upon treatment with lithium tetramethylpiperidide, but mixtures of a- and y-substitution products are obtained upon treatment of this anion with alkylating agents20. Consequently, this route to a-substituted allylboron compounds appears to be rather limited in scope. 

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.). 

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. 

The poor diastereoselectivity of the reactions of chiral aldehydes and achiral allylboronates appeared to be a problem that could be solved by recourse to the strategy of double asymmetric synthesis.f Our studies thus moved into this new arena of asymmetric synthesis, our objective being the development of a chiral allylboron reagent capable of controlling the stereochemical outcome of reactions with chiral aldehydes independent of any diastereofacial preference on the part of the carbonyl reaction partner. 

Reactions with Achiral Aldehydes. The reaction of tartrate allylboronates with achiral aldehydes proceeds with moderate to excellent enantioselectivity (60-92% ee) and high yield (80-90%). Simple aliphatic aldehydes give good enantioselectiv-ities (decanal 86% ee, CyCHO 87% ee, eq 2), while p-alkoxy and conjugated aldehydes give diminished selectivities (60-80% ee) (eq 3). The enantioselectivity is highly temperature and solvent dependent. Best results for reactions with the vast majority of aldehydes are obtained in toluene at —78 °C. 4°A molecular sieves are included to ensure that the reaction is anhydrous. Other tartrate esters (e.g. diethyl tartrate) may also be used without loss of enantioselectivity. 

The tartrate-derived allylboronate reagents in the best cases compare favorably with other allylboration reagents in their reactions with both achiral and chiral aldehydes (e.g. B-Allyldi-... 

Related Allylboronate Reagents. A stereoselective synthesis of anti 1,2-diols has been achieved by using a DIPT-modified ( )-y-[(cyclohexyloxy)dimethylsilyl]allylboronate reagent. This reagent is best applied in double asymmetric reactions with chiral aldehydes such as o-glyceraldehyde acetonide (eq 9). 

As with the corresponding allylboronate, the enantioselectivity of reactions with (3-alkoxy and conjugated aldehydes are lower (55-74% ee). In the case of benzaldehyde (91%, 66% ee), selectivity can be improved by the use of the derived chromium tricarbonyl complex. The homoallylic alcohol is obtained after... 

Roush asymmetric allylation Reaction of allylboronates with aldehydes to give homoallylic alcohols. 386... 

The chiral allyl- and 2-butenylboronates derived from tartrate esters (Chart 10-5) have been used in combination with a wide variety of chiral aldehydes to produce homoallylic alcohols in high yield and moderate to high enantioselectivity [124], The results obtained from reaction of selected chiral aldehydes (Chart 10-6) with the tartrate-modified allylboronates 195 and 197 (Chart 10-5) are shown in Table 10-20. As with the achiral aldehydes, the highest enantioselectivities are obtained when the chiral aldehydes are combined with allylboronate 197. A strong reagent-induced selectivity is apparent, but is nevertheless dependent on the intrinsic bias of the aldehyde. 

Scheme 11-10). It should be noted that glyeeraldehyde derivatives are outstanding substrates for the tartrate ester-modified allylboronates [118]. Aldehyde 261, derived from 260 in two steps, underwent a highly stereoselective (selectivity = >99 1) allylation reaction with the Brown Ipc2BAllyl reagent 195 [112, 113] (an in-depth discussion of the synthesis and use of this reagent appears in Section... 

The synthesis of bis-pyran 340 was initiated by the allylation reaction of aldehyde 336b with the allylboron reagent derived from allylstannane (S)-335 and... 

---