Roush asymmetric allylation

According to Roush, the asymmetric induction can be explained by an unfavorable electronic repulsive interaction between the nonbonding electron pair of the aldehyde and ester that destabilizes transition state B relative to A.  

The total synthesis of the 20-membered macrolide (+)-lasonolide-A was undertaken by S.H. Kang and co-workers. During the construction of the C15-C25 subunit, they utilized the Roush asymmetric allylation reaction to introduce the C21 and C23 stereocenters. First, (R,R)-diisopropyltartrate derived allylboronate was used to provide the (S)-homoallylic alcohol with 78% ee. A second asymmetric allylation was achieved utilizing the (S,S)-diisopropyltartrate-derived allylboronate to form the (R)-homoallylic alcohol with a 91% ee. 

Stevastelins are depsipeptides exhibiting immunosuppressant activity. The first total synthesis of stevastelin B was described by Y. Yamamoto and co-workers. To construct four consecutive stereocenters, the Evans aldol reaction and the Roush asymmetric allylation were utilized. In the allylation step, the authors used (S,S)-diisopropyltartrate-derived ( )-crotyl boronate. The anti homoallylic alcohol product formed as the only diastereomer. 

Theodorakis and co-workers reported the total synthesis of clerocidin, a diterpenoid antibiotic. To form the C12 stereocenter and the diene moiety, they applied an asymmetric homoallenylboration method. The reaction of the aldehyde and (S,S)-diisopropyltartrate-derived homoallenyl boronate provided the alcohol with a 6 1 diastereoselectivity and 83% yield. 

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

Related reactions Roush asymmetric allylation, Sakurai allylation ... 

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. 

Noncarbohydrate starting materials may also be used for preparing carbasugars. For example, Roush s et al. asymmetric allylation of chiral aldehyde 244 gave diene 245. Subsequent RCM catalyzed by [Ru]-II and dihydroxylation allowed access to... 

The use of tartrates as chiral auxiliaries in asymmetric reactions of allenyl bor-onic acid was first reported by Haruta et al.69 in 1982. However, it was not for several years that Roush et al.,70 after extensive study, achieved excellent results in the asymmetric aldol reactions induced by a new class of tartrate ester based allyl boronates. 

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. 

For a comprehensive review of synthetic applications of asymmetric boron allylation reactions, see Chemler, S. R. Roush, W. R. in Modem Carbonyl Chemistry Otera, J., Ed. Wiley-VCH Weinheim, Germany, 2000 Chapt. 11. 

A final example of the use of tartrate-derived crotylboronates in natural product synthesis is illustrated in the formal total synthesis of ikarugamicin (Scheme II-11) [179]. Here, Roush and Wada used the asymmetric crotylboration of meso-(t/" -2,4-hexadien-1,6-dial)iron tricarbonyl 266 with (S,S)-(E)-219 to set three stereocenters in their synthesis of the a,s-indacene unit of ikarugamycin. This key reaction provided 267 in 90% yield and >98% ee. Homoallylic alcohol 267 was converted to the allylic acetate 268, which underwent stereoselective ethylation with EtsAl with retention of stereochemistry. The resulting adduct 269 was subsequently elaborated to as -indacene unit 271 through a 15-step synthetic sequence, including the intramolecular Diels-Alder reaction of 270. 

Besides aUylsUanes or stannanes, allyl boron species have found widespread apphcations in synthesis. The Roush crotylation is a very well-estabhshed method with a broad substrate scope, and is therefore commonly used in organic synthesis [73]. The following example depicts a reversal in enantioselectivity induced by a cobalt complex present in the substrate. Roush et al. reported that the use of metal carbonyl complexes as substrate surrogates led to an improvement of enantioselectivity in the asymmetric crotylation of the respective aldehydes. These results were attributed to electronic effects exerted by the metal complexes that stabilize the transition state of the crotylation reaction (Scheme 3.47) [74]. 

There have been numerous Other applications of BINOL-Ti-catalyzed ally-lation reactions in complex molecule syntheses [30, 32], In the construction of the terminal portion of mucocin, Evans documented the asymmetric addition of an allylstannane to unsaturated aldehyde 202, giving adduct 203 in 98 2 dr (Equation 14) [125]. In another example, Roush disclosed the addition of an allylstannane to aldehyde 204, en route to the synthesis of the superstolides (Equation 15) [126]. These examples underscore the Ti-cata-lyzed enantioselective allylation process as a general approach to useful, functionalized chiral fragments. 

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