Allylation using crotylboronates

In earher work, the Hall group found that catalytic amounts of triflic acid promoted the addition of aUylboronates to aldehydes [132], While aUylboration reactions catalyzed by chiral Lewis acids in general led to only low levels of enan-tioselection [133], Hall found that chiral LBA 1 catalyzes the asymmetric addition of allyl- and crotylboronates to various aldehydes to provide products in excellent yields and moderate to high ee s (Scheme 5.71) [134]. Further, double diastereose-lective crotylboration could also be achieved with high selectivities using the... 

In general, as the aldehyde a-substituents become more sterically demanding, it becomes more difficult to obtain useful levels of diastereoselection for the product expected from reagent control in mismatched double asymmetric reactions between chiral aldehydes and chiral allyl- and crotylboronates [203]. For this reason, in natural product synthesis, mismatched double asymmetric reactions should be designed to occur early rather than late in a synthetic sequence. 

Rauniyar, V. Hall, D. G. Catalytic Enantioselective and Catalyst-Controlled Diastereofacia 1-Selective Additions of Allyl- and Crotylboronates to Aldehydes Using Chiral Bransted Acids. Angew. Chem. hit. Ed. 2006,45,2426-2428. 

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. 

Chiral crotylboronates (216) and (217) were among the first chiral allyl metal reagents to be used in double asymmetric reactions. The example in Scheme 47, however, shows that (217) induces only modest changes in the stereoselectivity of the reactions of (249), thus underscoring the need for highly enantioselective chiral reagents. 

Results of reactions of chiral a-methyl aldehydes and several chiral crotyl- and allyl-boron reagents are summarized in Tables 8 and 9. It is apparent from these data that the Brown (Ipc)2B(crotyl) and (Ipc)2B(allyl) reagents (51), (52) and (219) consistently give excellent results for the synthesis of each product diastereomer (Table 8, entries 3-6, 11, 16, 20, and 24 Table 9, entries 1,2, 10 and 18). This is true also for their reactions with chiral a- and 3-alkoxy aldehydes (Scheme 49).i. i4S-i50 Thg tartrate crotylboronates (18) and (19) also display excellent selectivity in the synthesis of crotyl diastereomers (136), (137) and (139) (Table 8, entries 7,10,13,17,25 and 28), but are much less selective for the syndesis of crotyl diastereomer (138), especially from -alkoxy-substituted aldehydes such as (253). Tartrate allylboronate (224) is also less effective than (Ipc)2Ballyl (219) for the synthesis of (257) and (258) in Table 9, and of (266) and (267) in Scheme 49.Substantial improvements in selectivity have been realized by using the taitramide-based allylboronate (228), and the results with this reagent (Table 9, entries 4, 7, 9, 12, 14, 17, 20 and 22) compare very favorably with those obtained with (219). The data... 

The synthesis and use of tartrate-modified allylboronate 1 was first reported by Roush and co-workers in 1985. The synthesis and use of the corresponding (E)- and (. -crotylboronate reagents 2 and 3 was published by Roush and co-workers shortly thereafter. The ease of synthesis, stability and efficient reactivity of these reagents offers advantages over many other allyl- and crotylmetal reagents. Roush and co-workers have extensively explored the enantioselective allylations with achiral aldehydes as well as the... 

Intramolecular versions of the above allylic substitutions have been developed. For example, Hoffmann and Dresely reported in 1986 that treatment of the optically active y-siloxyalkenylboronate 47 provides the useful a-chloro-( )-crotylboronate 48 with an almost perfect level of chirality transfer (Equation 27) [71]. Schlapbach and Hoffmann more recently reported the preparation of a-sulfonamido allylboronates by sequential treatment of 47 with SOCI2 and the corresponding lithiated sulfon-... 

FIGURE 10.8. Commonly used allyl/crotylboron reagents. 

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