Boronate tartrate-derived

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. 

The characteristic feature of the aforementioned oxazaborolidine catalyst system consists of a-sulfonamide carboxylic acid ligand for boron reagent, where the five-membered ring system seems to be the major structural feature for the active catalyst. Accordingly, tartaric acid-derived chiral (acyloxy)borane (CAB) complexes can also catalyze the asymmetric Diels-Alder reaction of a,P-unsaturated aldehydes with a high level of asymmetric induction [10] (Eq. 8A.4). Similarly, a chiral tartrate-derived dioxaborolidine has been introduced as a catalyst for enantioselective Diels-Alder reaction of 2-bromoacrolein [11] (Eq. 8A.5). 

Kinetic resolution can be accomplished by addition of allyl boronates to aldehyde groups adjacent to the tricarbonyliron fragment [59]. For the synthesis of ikaruga-mycin, Roush and Wada developed an impressive asymmetric crotylboration of a prochiral meso complex using a chiral diisopropyl tartrate-derived crotylborane (Scheme 1.25) [60]. In the course of this synthesis, the stereo-directing effect of the tricarbonyliron fragment has been exploited twice to introduce stereospedfically a crotyl and a vinyl fragment. 

Phosphine-boronates featuring rigid backbones have been accessed by condensing adequately functionalized phosphines and boronic acids. This strategy was first developed by Kagan6 and Jacobsen62 who independently reported the synthesis of the tartrate-derived boraDIOP compounds 50 (Scheme 32). The key precursor 49 was readily obtained by acidic hydrolysis of the diphosphine (R,R)-DIOP (DIOP = 2,3-O-isopro-pylidene-2,3-dihydroxy-l,4-bis(diphenylphosphino)butane). Upon reaction with PhB(OH)2 or PhBCU the phosphine-boronate 50a was isolated in... 

An instance of the enantiofacial preference of the reacting partner overwhelming that of the reagent is shown in the case of the reagent s reaction with the tartrate-derived allyl boronates shown. Even in the mismatched case, this example of reagent-based stereocontrol affords a greater than 10 1 selectivity for the syn product (eq ). ... 

Chelation cf prochiral dienophiles by chiral boron, aluminum and titanium Lewis acids 4.13,33 Tartrate-derived chiral acyloxyborane catalysts... 

Fig. 16. The general structural characteristics of amino acid and tartrate derived ligands for boron catalysts...

Asymmetric allylation and crotylation, synthetically equivalent to the aldol reaction, have been extensively studied and have become a very useful procedure for preparation of propionate units. Among various chiral ligands on boron-developed, isopinocampheyl- and tartrate-derived reagents, 51 and 52, which were developed by Brown et al. [18] and Roush et al. [19], respectively, are the most commonly used (Scheme 7). Reaction of aldehyde with (Sl-Sla or 52a gave anu -adduct 54, while that using (Z)-51b or 52b afforded syn-adduct 53 with high asymmetric selectivity. 

The C14-C19 and C33-C37 segments (188 and 185) [116] Epoxide 189 (Scheme 25) available from (-f-)-dimethyl tartrate [121, 122] served as starting material for the construction of both segments. For the synthesis of 185,189 was converted to isopropylidene aldehyde 190 as shown. Evan s aldol procedure [35,36] with aldehyde 190 and boron enolate derived from oxazolidone 21 gave... 

In 1978, Hoffmann reported enantioselective allylation reactions of aldehydes with a camphor-derived chiral boronate 13 (Equation 1) [55]. Three classes of chiral boron reagents that furnish allylation products with very high levels of enantioselectivity have emerged Brown s diisopinocampheyl or diisocaranyl allyl boranes [35-41], Roush s tartrate-derived boronates [33, 42-48], and Hoffmann s "a-chiral boronates [56-61],... 

The tartrate-derived allyl and crotyl boronates 25 developed by Roush [33, 42-48] represent a convenient and elegant alternative to the terpene-derived boranes described above, as a consequence of their ease of handling and configurational stability (Equation 3). Representative examples are summarized in Table 5.2 [42, 45, 47]. These reagents have also enjoyed widespread applications in diastereoselective, reagent-controlled additions to chiral aldehydes, displaying superb levels of diasteroinduction [43, 44, 48], An explanation for the observed stereoselectivity has been proffered by Roush [32] and supported by ab initio calculations [62] minimization of lone pair/lone pair interactions as well as an attractive interaction between the ester lone pairs and the polarized aldehyde are believed to result in a preference for transition state structure 26. 

Table 5.2 Enantioselectivity with tartrate-derived boronates 25 [42. 45, 47).

The tartrate-derived allylboronates 25 are best prepared by treatment of triisopropyl borate with the appropriate carbanion. The crude diisopropyl boronate 28 is then treated with either enantiomer of diisopropyl tartrate (DIPT) to effect rapid transesterification, giving the boronates 25, 29, and 30 (Equation 4) [47],... 

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

Chiral addition of allyl metals to imines is one of the useful approaches toward the synthesis of homoallylic amines. These amines can be readily converted to a variety of biologically important molecules such as a-, / -, and y-amino acids. Itsuno and co-workers utilized the allylborane 174 derived from diisopropyl tartrate and cr-pinene for the enantioselective allylboration of imines. The corresponding iV-aluminoimines 173 are readily available from the nitriles via partial reduction using diisobutylaluminium hydride (DIBAL-H) <1999JOM103>. Recently, iV-benzyl-imines 176 have also been utilized for the asymmetric allylboration with allylpinacol boronate 177 in the presence of chiral phosphines as the chiral auxiliaries to obtain homoallylic A -benzylamines 178 in high yield and selectivity (Scheme 29) <2006JA7687>. 

Although the asymmetric aldol reaction of benzaldehyde and di ketene has been reported with a catalyst generated from di-iso-propyl tartrate and iso-propanol, low induction and low yields were observed for the d-hydroxyl-y5-keto ester 27 [8], Low induction was also observed for aldol reactions mediated by chiral aluminum catalysts generated from a-amino acids [9]. These types of catalyst have been very successful when employing boron as the Lewis acid, as illustrated in the aldol reaction of ketene acetal 10 with the boron catalyst 31 derived from (5)-valine (Sch. 4) [9,10]. Catalysts derived from A-tosyl-(5 )-valine and Et2AlCl and i-BuyAl were relatively ineffective (< 15 % ee) [9]. 

By a similar method, the (Z)-crotylborate is synthesized from cA-2-butene in 70-75% yield with a 98% isomeric purity. The tartrate esters of allylboronic acids are an excellent reagent for asymmetric allylboration of carbonyl compounds. Allyl(diisopinocampheyl)borane [51] and the allylic boron derivatives of ester and amide, such as camphordiol [52], pinanediol [53], 1,2-diphenyl-1,2-ethylenediamine [54], have also been successfully used for asymmetric allylboration of carbonyls. 

Boron derivatives of heteroarenes are also viable partners. A Suzuki reaction of a vinyl triflate 2.282, prepared by enantioselective enolate formation, with a benzothiophenyl boronic acid 2.283 was used to prepare 12.75 kg of a tropane derivative 2.284 (as its tartrate salt) as a drug candidate (Scheme 2.90). ... 

Different studies were carried out to develop diastereocontrolled versions of these Diels-Alder reactions. Better results were obtained when an optically pure diol was used as chiral director. The tandem reaction involving a 1,3-dienylboronate derived from tartrate esters proceeded with 70% enantiomeric excess (Scheme 9.35) [76]. The hetero-Diels-Alder reaction of enantiomerically pure (-t)-pinanediol 1,3-dienyl-boronate with an azo dienophile gave the J -configured endo cycloadduct as the single stereoisomer [77]. 

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