Allyl borane

Hydrolysis of 1-boronylallylstannanes, available by stannylation of alkenyl and allyl boranes. gives (Z)-allylstannanes stereoselectively34. 

For reviews, see Hoffmann, R.W. Niel, G. Schlapbach, A. Pure Appl. Chem., 1990, 62 1993 Pelter, A. Smith, K. Brown, H.C. Borane Reagents Academic Press NY, 1988, p 310. For a review of allylic boranes, see Bubnov, Yu.N. Pure Appl. Chem., 1987, 21, 89, For an example that proceeds with asymmetric induction, see Buynak, J.D. Geng, B Uang, S. Strickland, J.B. Tetrahedron Lett., 1994, 35, 985. 

Allylic derivatives are particularly important in the case of boranes, silanes, and stannanes. Allylic boranes effect nucleophilic addition to carbonyl groups via a cyclic TS that involves the Lewis acid character of the borane. 1,3-Allylic transposition occurs through the cyclic TS. 

Allylic boranes such as 9-allyl-9-BBN react with aldehydes and ketones to give allylic carbinols. The reaction begins by Lewis acid-base coordination at the carbonyl oxygen, which both increases the electrophilicity of the carbonyl group and weakens the C-B bond to the allyl group. The dipolar adduct then reacts through a cyclic TS. Bond formation takes place at the 7-carbon of the allyl group and the double bond shifts.36 After the reaction is complete, the carbinol product is liberated from the borinate ester by displacement with ethanolamine. Yields for a series of aldehydes and ketones were usually above 90% for 9-allyl-9-BBN. 

The allylation reaction has been extended to enantiomerically pure allylic boranes and borinates. For example, the 3-methyl-2-butenyl derivative of (Ipc)2BH reacts with aldehydes to give carbinols of greater than 90% e.e. in most cases.39... 

Mechanistic studies have suggested that the TS involves bonding of Sc3+ to one of the boronate oxygens,57 which is consistent with the observation that the catalysts do not have much effect on the rate of allylic boranes. The phenyl substituent on the... 

Scheme 9.3 illustrates some examples of syntheses of allylic carbinols via allylic boranes and boronate esters. Entries 1 and 2 are among the early examples that... 

Scheme 9.3. Addition Reactions of Allylic Boranes and Carbonyl Compounds...

Although the allylation reaction is formally analogous to the addition of allylic boranes to carbonyl derivatives, it does not normally occur through a cyclic TS. This is because, in contrast to the boranes, the silicon in allylic silanes has little Lewis acid character and does not coordinate at the carbonyl oxygen. The stereochemistry of addition of allylic silanes to carbonyl compounds is consistent with an acyclic TS. The -stereoisomer of 2-butenyl(trimethyl)silane gives nearly exclusively the product in... 

TS, which is usually based on the chair (Zimmerman-Traxler) model. This pattern is particularly prevalent for the allylic borane reagents, where the Lewis acidity of boron promotes a tight cyclic TS, but at the same time limits the possibility of additional chelation. The dominant factors in these cases are the E- or Z-configuration of the allylic reagent and the conformational preferences of the reacting aldehyde (e.g., a Felkin-type preference.)... 

The intramolecular rearrangement of allylic boranes (Eq. 5) clearly involves a multiple boron-carbon bond in the transition state (45), as the boron 2pz-orbital interacts with the 7r-bonding MO. 

However, the classical version of the ABAC, when triallyl-, trimethallyl-, or tricrotylborane are involved in the reaction with RR1CHC=CH (e.g., propargylic ethers), can be applied only for the synthesis of 1-boraadamantane derivatives 35, 3,5-dimethyl- 36 and 4,6-dimethyl-l-boraadamantanes 37 (Scheme 7). Hence, the stmctures of the final cage compounds are rigidly restricted by the stmctures of the starting allylic boranes. 

As discussed in Section 3.3.2, Corey demonstrated the utility of compound 55, prepared from 1,2-diphenyl-1,2-diamino ethane 54, as a chiral auxiliary for asymmetric aldol reaction. In a similar manner, his group utilized this compound 55 in both (R,R)- and (A,A)-forms for allylation reactions. Treatment of 55 with allyltributyltin in dry CH2CI2 at 0°C and then 23°C for 2 hours gives chiral allyl-borane 135. In this process, both the (R,R)- and (A,A)-forms can be obtained and applied in asymmetric allylation reactions. Thus, treatment of... 

Scheme 3-47. Reaction of aldehydes with chiral allyl boranes 135. Reprinted with permission by Am. Chem. Soc., Ref. 41.

In addition to the predominant allyl and crotyl reagents, a large nnmber of allylic borane 1 and boronate derivatives 2 (Eq. 1) with varions snbstitnents (R -R" ) have been reported. Interested readers can refer to the comprehensive Tabnlar Snrvey at the end of this monograph, which covers the literatnre np to the end of 2005. Several reviews on allylic boron componnds and other allylmetal reagents and their additions to carbonyl compounds and imines have been written prior to this one," " and these sonrces may be consnlted if a more in-depth historical perspective is desired. 

The immediate products of additions between carbonyl substrates and allylic boranes 1 or boronate derivatives 2 are borinate or borate esters, respectively. To cleave the covalent B-O bond in these intermediates (structme 6, Scheme 1) and to obtain the desired free alcohol, a hydrolytic or oxidative work-up is required. This issue is discussed in detail in the section Work-Up Conditions . In the interest of simplifying chemical equations, specific work-up conditions are not inclnded in most of the examples highlighted in this chapter. 

Unlike aldehydes and ketones, allylic boron compounds are not ubiquitous, commercial organic substrates. There are several methods for the preparation of allylic boronates, however, and many of these have been developed in the past decade. This topic has been reviewed recently " so only the most common methods are emphasized in this section. As a result of the lesser stability of allylic boranes, methods to access these reagents are more limited and it is generally easier to prepare allylic boronates with a wide range of functional groups. 

From Hard Allylic Organometallics. The most common preparation of allylic boranes and boronates is the addition of a reactive allylic metal species to a borinic or boric ester, respectively (Eqs. 10 and 11). Preparations from allyllithium, " " allylmagnesium, and allylpotassium " ° reagents are all well known. These methods are popular because the required allylic anions are quite easy to prepare, and because they generally lead to high yields of products. 

Allylic boronates are more stable to atmospheric oxidation and are thns mnch easier to handle than the corresponding allylic boranes. The stability of the boronate reagents arises from the partial donation of the lone pairs of electrons on the oxygen atoms into the empty p-orbital of boron. This mesomelic effect is responsible for the npfield shift of the boron atom in NMR compared to that of allylic boranes (compare allylboronate 31 and allylborane 32). ... 

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-... 

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. 

To improve the levels of selectivity in additions to chiral aldehydes, it is possible to resort to the tactic of double diastereoselection with the use of chiral allylic boranes and boronates (see section Double Diastereoselection ). Bis(isopinocampheyl) allylic boranes and the tartrate allylic boronates (see following section), in particular, are very useful in the synthesis of polypropionate natmal products by reaction with a-methyl and a-alkoxy functionalized aldehydes. 

Chiral Dialkylboranes. Several allylic boranes have been developed as chiral auxiliary reagents (Fig. 5). The introduction of terpene-based reagents such as 12 and 64-68 has been pioneered by H.C. Brown, and the most popular class remains the bis(isopinocampheyl) derivatives (structures 12, 64-66). A wide variety of substituted analogs have been reported, including the popular crotylboranes but also a number of other reagents bearing heteroatom-... 

Figure 5. Chiral allylic boranes used as chiral auxiliary reagents in enantioselective additions to carbonyl compounds. (Only one isomer is shown for simplicity. For reagents 12 and 64-66, (—)-Ipc is shown.).

The enantioselectivity of these reagents is explained by comparison of transition structures 72 and 73 shown in Scheme 7. The disfavored transition structure 73 leading to the minor enantiomer displays a steric interaction between the methylene of the allylic unit and the methyl group of one of the pinane units. Unlike the tartrate boronates described above, the directing effect of the bis(isopinocampheyl) allylic boranes is extremely powerful, giving rise to high reagent control in double diastereoselective additions (see section on Double Diastereoselection ). 

Scheme 7. Model for absolute stereoinduction in additions of (—)-bis(isopinocampheyl) allylic boranes to aldehydes.

The powerful directing effect of bis(isopinocampheyl) allylic boranes has been put to great use in the context of several applications of double diaster-ereoselective allylations in the total synthesis of natural products. As discussed in a previous section, the Brown allylation can be exploited to overcome the stereodirecting effect of chiral a-stereogenic aldehydes, including a-aUcoxy substituted ones. Thus, the simple allylation of aldehyde 154 provides as major product the desired diastereomer needed towards a total synthesis of brasilenyne (Scheme 14). The yield and stereoselectivity is even increased to over 97 3 under the low-temperature, magnesium-free conditions described before. 

Addition reactions of allylic boron compounds have proven to be quite general and useful. Several methods for synthesis of allylic boranes and boronate esters have been developed.36 37 The reaction has found some application in the stereoselective synthesis of complex structures. 

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