Roush crotylation

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]. 

Treatment of 122 with (R,R)-tartrate crotyl-boronate (E.R.R)-W 1 provides the alcohol corresponding to 123 with 96% stereoselectivity. Benzylation of this alcohol yields 123 with 64% overall yield. The crude aldehyde intermediate obtained by ozonolysis of 123 is again treated with (Z,R,R)-111 (the second Roush reaction), and a 94 5 1 mixture of three diastereoisomers is produced, from which 124 can be isolated with 73% yield. A routine procedure completes the synthesis of compound 120, as shown in Scheme 3-44. Heating a toluene solution of 120 in a sealed tube at 145°C under argon for 7 hours provides the cyclization product 127. Subsequent debromination, deacylation, and Barton deoxygenation accomplishes the stereoselective synthesis of 121 (Scheme 3-44). 

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. 

The substrate 7 had been previously synthesized by Roush using the crotylation method described above.14... 

For the synthesis of Olivomycin A. the Roush group used a crotyl ether to protect a phenolic hydroxyl group,42 In the final lap of the synthesis, deprotection of the phenolic crotyl ether in 226.1 was achieved with Pd(0) and tributylstan-nane [Scheme 4.226]. No harm befell the sensitive cyclopentylidene acetal and chloroacetate groups. 

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. 

Noteworthy among these examples is the ability to achieve high diastereoselec-tivity for both the 3,4-syn and 3,4-anti isomers, almost independent of the chirality sense of the aldehyde. Comparison of several examples show the expected trends for matched and mismatched pairs (c/. entry pairs 1/2, 4/6, 5/7, 9/12, 16/17). Note that either 3,4-anti diastereomer can be obtained with 96% ds (entries 8 and 12) the two 3,4-syn isomers are also available selectively (entries 13-16 and 17), although only one ligand (5.1i) is selective for the 3,4-syn-4,5-syn product (entry 17) that is a mismatched pair cf. entry 16). Note that with Roush s tartrate ligand (Figure 5.1c), the -crotyl mismatched pair is more selective than the matched pair (entries 8/11 for a rationale, see ref. [33]), and the matched and mismatched pair give the same major product isomer with the Z-crotyl compound (entries 14/15). 

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. 

A total synthesis of (+)-Janomycin (121) has been reported, key steps being asymmetric crotylation of the precursor aldehyde (using Roush s tartrate boronate) generating 119, and then elaboration to the C-glycoside 120 (Scheme... 

The synthesis of the alcohol 8 started with protection of known homoallyUc alcohol 10 as its MPM ether and subsequent cleavage of the double bond to give the aldehyde 11 (Scheme 2). Roush asymmetric crotylation of 11 by using chiral crotyl boronate 12 provided the alcohol 13. Silylation of 13 followed by removal of the MPM group led to the alcohol 14, which was inverted via Mitsunobu reaction to afford the alcohol 8. Here we intentionally used the homoallylic alcohol 10 with incorrect configuration as the starting material and synthesized 8 in a circuitous manner. This was because asymmetric crotylation of ent-11, which we initially tried, only provided the alcohol 15 as an inseparable 1 1 mixture of diastereomers. 

In their report of crotylation reactions with cobalt carbonyl complexed aldehyde not only the enantioselectivity is improved, but it is also reversed. As can be seen in Scheme 3.47 the reaction of aldehyde 223 with the crotylation reagent 224 results in moderate enantioselectivities. If in contrast, cobalt complex 227 of the parent aldehyde 223 was used the opposite enantiomer was obtained, and in the latter case an improved selectivity was achieved. The double bond introduced via this crotylation is required for the intramolecular Pauson-Khand reaction that Roush and coworkers carried out [75]. 

Earlier, Professor Roush had optimized the crotylation of the protected alaninal 7. In this case, the Brown reagent 8 delivered the desired Felkin product 9. Protection followed by ozonolysis gave the aldehyde 10. Crotylation with the Roush-developed tartrate 11 then gave the alkene 12, setting the stage for conversion to the iodide 13. Coupling of 13 with 6 completed the preparation of 14. 

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. 

A number of applications in the synthesis of complex structures have been documented. The versatility of the Roush allylboron reagents is demonstrated in the diverse range of substrates that have been successfully employed. In a formal total synthesis of ikarugamycin, the diene in 31 was protected as the iron complex, and the aldehyde in 31 underwent crotylation to afford 33 in 98% ee (Equation 5) [63]. 

A few examples showcasing double stereodifferentiation phenomena are outlined below. In the case of crotylation of a-alkoxy-substituted aldehyde 72, Roush observed a reversal of facial selectivity with either enantiomer of the chiral ( )-crotylboronate reagent 29 (Scheme 5.13) [48]. Similarly, Brown found that the pinene-derived crotyl boranes 76 and 77 provide access to all four stereotriads 78-81 with impressive stereoselectivity with use of either the ( )- or the (Z)-crotyl reagent (Scheme 5.14) [77]. 

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