Allylic Boron Reagents

Another extensively developed group of allylic boron reagents for enantioselective synthesis is derived from tartrates.42... 

The synthesis in Scheme 13.49 features use of an enantioselective allylic boronate reagent derived from diisopropyl tartrate to establish the C(4) and C(5) stereochemistry. The ring is closed by an olefin metathesis reaction. The C(2) methyl group was introduced by alkylation of the lactone enolate. The alkylation is not stereoselective, but base-catalyzed epimerization favors the desired stereoisomer by 4 1. 

Over the past two decades, chiral allyl- and crotyl-boron reagents have proved to be extremely valuable in the context of acyclic stereoselection. The development of superior allyl-boron reagents, which can give enantio- and diastereoselectivities approaching 100%, has become both challenging and desirable.68... 

One of the main reasons for the popularity of allylic boron reagents in stereo-controlled synthesis is that their additions to aldehydes are reliably highly stereoselective and the ontcome is predictable. The diastereospecificify of the reaction was first recognized by Hoffmann and Zeiss using both E- and Z-crofylboronates... 

A number of other functionalized allylic boron reagents can be made using allyhnetal intermediates, including E-3-silyl-substituted reagents, " ° " exemplified by the bis(Ipc) derivative 13" (Eq. 17), and the useful Z-3-alkoxy-substituted reagents," exemplified by 14" (Eq. 18). The double bond geometry of 14 arises from the chelated alkyllithium intermediate employed in... 

The boron-oxygen mesomeric effect described in the previous section explains the lower reactivity of allylic boronates towards carbonyl compounds compared to that of allylic boranes. The use of Lewis acids, however, allows boronate derivatives, including hindered ones, to react at temperatures comparable to the analogous boranes. As described above (see section Mechanism and Stereochemistry ), the most reactive allylic boronates are those with the most electrophilic boron centers.The nucleophilicity of the y-position of an allylic boron reagent (the position that forms the new C-C bond with the aldehyde) is also important to the reactivity of the reagent. For example, allylic boronates with... 

The addition of allylic boron reagents to carbonyl compounds first leads to homoallylic alcohol derivatives 36 or 37 that contain a covalent B-O bond (Eqs. 46 and 47). These adducts must be cleaved at the end of the reaction to isolate the free alcohol product from the reaction mixture. To cleave the covalent B-0 bond in these intermediates, a hydrolytic or oxidative work-up is required. For additions of allylic boranes, an oxidative work-up of the borinic ester intermediate 36 (R = alkyl) with basic hydrogen peroxide is preferred. For additions of allylic boronate derivatives, a simpler hydrolysis (acidic or basic) or triethanolamine exchange is generally performed as a means to cleave the borate intermediate 37 (Y = O-alkyl). The facility with which the borate ester is hydrolyzed depends primarily on the size of the substituents, but this operation is usually straightforward. For sensitive carbonyl substrates, the choice of allylic derivative, borane or boronate, may thus be dictated by the particular work-up conditions required. 

Additions of allylic boron reagents have been reported on a very wide range of classes of functionalized aldehydes. Some types of aldehydes, however, are very reactive and may lead to side-reactions. For example, p,Y-unsaturated aldehydes are notoriously difficult substrates but an indirect procedure for their in situ generation leads to clean products of allylboration. Although most examples... 

The presence of a stereogenic center on the aldehyde can strongly inlinence the diastereoselectivity in allylboration reactions, especially if this center is in the a-position. Predictive rules for nucleophilic addition on snch a-snbstitnted carbonyl substrates such as the Felkin model are not always snitable for closed transition structures.For a-substituted aldehydes devoid of a polar substituent, Roush has established that the minimization of ganche-ganche ( syn-pentane ) interactions can overrule the influence of stereoelectronic effects. This model is valid for any 3-monosubstituted allylic boron reagent. For example, althongh crotylboronate (E)-7 adds to aldehyde 39 to afford as the major prodnct the diastereomer predicted by the Felkin model (Scheme 2), " it is proposed that the dominant factor is rather the minimization of syn-pentane interactions between the Y-snbstitnents of the allyl unit and the a-carbon of the aldehyde. With this... 

Figure 6. Chiral a-substituted allylic boron reagents.

Many of the recent advances in synthetic applications of allylic boron reagents have focused on the use of these reagents as key components of tandem reactions and one-pot sequential processes, including multicomponent reactions. The following examples briefly illustrate the range of possibilities. Most cases involve masked allylboronates as substrates, and the tandem process is usually terminated by the allylboration step. 

With only a small number of substrate types are the tartrate-based allylic boronate reagents enantioselective enough for applications in the control of... 

Several allylic boron reagents have been recently employed in a series of doubly diastereoselective additions toward a synthesis of mycalamide. " Thus,... 

Additions of allylic boron reagents are typically performed under experimentally simple conditions, and under a wide range of temperatures that is dictated by the reactivity of the particular reagent employed. Work-up conditions are discussed in a previous section. For the reaction itself, uncatalyzed additions can be performed in a wide variety of aprotic solvents. Non-coordinating solvents usually lead to shorter reactions times, but the identification of an optimal solvent in stereoselective additions is rather unpredictable and may require coordinating... 

To explain the stereochemical outcome of the reaction of allylic boron reagents with carbonyl compounds, Houk and Li carried out calculations on the transition structures of the model reaction of formaldehyde and allylboronic acid6 (Scheme 3.V). The bimolecular complex formed initially between allylboronic acid and formaldehyde would rearrange via a six-membered transition state to form an intermediate. Calculations show that chair transition state A is 8.2kcal/ mol more stable than twist-boat transition structure B, clearly confirming that the six-membered chairlike transition-state model is a legitimate scheme to predict the stereochemical outcome of the boron allylation reaction. 

Addition of allylmetals to C=X. Allylic boron reagents in which the boron atom is... 

Allylic Boron Reagents 361 Table 10-18. Double diastereoselection addition with chiral 2-butenylboranes 192. 

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