Allylic borinate

The other bases such as, LiNMCj, LiNEtj, and LiNPhj afford major products, 4, in which the OMe group has been nucleophilically displayed by the NRj group. On the contrary, lithium amides bases derived from the hindered secondary amines are highly proton selective to give the desired allylic borinate (3a) in high yield (Table 28.1) [8]. 

The effectiveness of these bases is correlated with the pK of respective amines [10]. Lithium amides derived from secondary amines whose pK values are in the vicinity of 30 (e.g., HN-t-BuSiMe, and HN(SiMej)2) are not suitable for efficient metalation. However, amines like HN-i-Prj, HNChx, and HN-/-PrChx, with pK, values around 35 bring efficient metalation. Moreover, the studies have revealed [8] that bulkiness of OR, as in Ib-d, gives lower yield of desired allylic borinate [11]. Consequently, combination of 9-methoxy-9-BBN and LiNChXj are found to afford the desired allylic borinate (3a) intermediate in excellent yields (Table 28.1) [8]. The 3a intermediate serves as a versatile intermediate in the synthesis of cyclooctane compounds (Chart 28.2) and thus solves the longstanding problem of high-degree strain arising from the powerful transannular interactions present in such systems [12]. 

A new protocol has been introduced to improve selectivity in allylboration of aldehydes. The readily available a-substituted allyl or crotyl pinacol boronic esters often give low A/Z-selectivity. Addition of -butyllithium followed by trapping of alkoxide with TFAA generates an allyl borinic acid, which gives very high -selectivity, and in some cases, this is the opposite of the standard conditions. The borinic ester intermediate was characterized by B-NMR. 

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... 

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. 

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. 

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. 

The oxidation of cholesteryl esters and low-density lipoproteins by free radicals has been reviewed.228 The use of bis(pentafluorophenyl)borinic acid as a strong Lewis acid allows efficient Oppenauer oxidation of allylic and benzylic alcohols using Bu CHO as oxidant.229 Saturated alcohols were only slowly oxidized and this allowed selective conversion of allylic alcohols in the presence of saturated alcohols. 

Methyl and 9-[(trimethylsilylmethyl)]-9-BBN derivatives are easily synthesized by the reaction of the corresponding lithium reagents with 9-methoxy-9-BBN. Unfortunately, such derivatives are spontaneously flammable in air, making them particularly hazardous to handle for the purpose of isolation. However, selective oxidation with anhydrous triethylamine A -oxide converts them to air-stable borinate esters which are efficient reagents for the methylation [149, 150] of haloalkenes or the syntheses of allylic and propargylic silanes (Scheme 2-52) [151]. 

Ishihara, K., Kurihara, H., Yamamoto, H. Bis(pentafluorophenyl)borinic Acid as a Highly Effective Oppenauer Oxidation Catalyst for Allylic... 

Scheme 33 illustrates the use of two standard persistent auxiliaries. The Evans oxazolidinone 33-1 [83] is highly versatile, i.e., suitable for enolate reactions and double bond additions alike. In the enolate alkylation case [reaction (99)] the high diastereoselectivity depends on the formation of a chelate 33-2 which fixes the reaction site in a defined conformation in which one of the diastereofaces is efficiently shielded. The removal of the auxiliary requires the chemoselective cleavage of the exo cyclic amide bond which is sometimes difficult to achieve. In boron mediated aldoltype additions [Scheme 34, reaction (100)] no chelate can be formed so that the extremeley high diastereoselectivity with which the syn-adduct 34-1 is formed must be due to some other effect, presumably allyl 1,3-strain on the stage of the enol borinate 34-1. 

Non-fluxional vinylic boranes do not react with carbonyl compounds. Nevertheless, the vinylic borane 29 reacts with acetone (2 h under reflux) yielding the Z-isomer of the homoallylic borinic ester 30b. The cw-configuration of the reaction product 30b corresponds to the following sequence of transformations (Scheme 2.11). The [1,7]-H shift in the vinylic borane 29 gives the allylic Z, Z-isomer 28d which immediately reacts with acetone before the equilibrium among the allylic isomers is established. On the other hand, cyclopentanone reacts directly with 29 under mild conditions yielding Z, Z-1,3,5-heptatriene 31 and borinic ester 32 (Scheme 2.12). Apparently 29 reacts with the enol form of cyclopentanone, and a direct splitting of the B-Q ,2 bond takes place. Similar reaction of 29 with acetic acid was used for the preparative synthesis of previously unknown hydrocarbon 31 (Scheme 2.12) [35]. 

The B-allyl-9-BBN derivatives react with carbonyl compounds to afford borinate esters, which on protonolysis using triethanolamine afford the corresponding homoallylic alcohols. Consequently, the allylboration sequence provides a synthetically useful alternative to the familiar Grignard s synthesis of these alcohols. However, the protonolysis by triethanolamine causes a problem in the isolation of homoallylic alcohol from the thick, air-sensitive, boron-containing mixture. Fortunately, treatment of pentane solution of borinate esters of 9-BBN with 1 equiv of ethanolamine results in the rapid formation of a fluffy white precipitate of ethanolamine 9-BBN adduct, which can be easily removed (Eq. 6.7) [1]. 

The intermediate borinic ester is not strongly basic as are intermediates in the lithium and magnesium allylation. 

Typical of allylboranes, B-isoprenyl-9-BBN reacts with acetaldehyde with allylic rearrangement to provide the borinate intermediate via a six-mem-bered transition state [43]. The alkaline hydrogen peroxide oxidation of this intermediate affords the desired 4-methylene-5-hexen-2-ol (Eq. 24.20). Table 24.20 [41] summarizes the results of representative aldehydes with B-isopre-nyl-9-BBN. 

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