Allylboron reagents, allylation with

Chiral, nonracemic allylboron reagents 1-7 with stereocenters at Cl of the allyl or 2-butenyl unit have been described. Although these optically active a-substituted allylboron reagents are generally less convenient to synthesize than those with conventional auxiliaries (Section 1.3.3.3.3.1.4.), this disadvantage is compensated for by the fact that their reactions with aldehydes often occur with almost 100% asymmetric induction. Thus, the enantiomeric purity as well as the ease of preparation of these chiral a-substituted allylboron reagents are important variables that determine their utility in enantioselective allylboration reactions with achiral aldehydes, and in double asymmetric reactions with chiral aldehydes (Section 1.3.3.3.3.2.4.). 

Enantiomerically pure homoallylic amines are very important chiral building blocks for the synthesis of natural products. However, enantioselective methods for homoallylamine are quite undeveloped. In 1995, Itsuno and co-workers reported the first example of enantioselective allylation of an imine (Scheme 7) [13]. The reaction of N-trimethylsilylbenzaldimine 19 with a chiral allylboron reagent 20 in ether at -78 °C afforded the corresponding homoallylamine 22 in 73% ee. 

The thiazole-substituted homoallylic alcohol 25 (Scheme 6) is a key intermediate, not only for RCM strategies, but also for other routes. Thiazole aldehyde 4 (Chapter 3) after homologation to enal 24 (90 % yield) [ 11,20) was subjected to asymmetric allylation with allylboron and tin reagents. Interestingly 25 with identical absolute stereochemistry was synthesized by Nicolaou et al. with (+)-IpC2B(allyl) in 96 % yield and > 97 % ee [13, 20], and by Danishefsky et al. with the enantiomeric (—)-Ipc2B(allyl) in 83 % yield and > 95 % ee [11], i.e. in one case an er-... 

A chiral allylic alcohol (3-carbanion equivalent has also been developed which utilizes a DIPT-modified E)-y-(dimethylphenylsilyl)allylboronate reagent. This method involves treating the product homoallylic alcohol with Dimethyl-dioxirane and subjecting the derived epoxide to an acid-catalyzed Peterson elimination. This sequence has been applied in the synthesis of the trioxadecalin ring system of the mycalamides (eq 10). ... 

The synthesis of bis-pyran 340 was initiated by the allylation reaction of aldehyde 336b with the allylboron reagent derived from allylstannane (S)-335 and... 

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... 

The allylboronate reagent 1 was used twice in the synthesis of (-)-lasubine I by Wang and Liao. (-)-Lasubine I (67) is a bioactive alkaloid isolated from the Lythraceae plant.(-)-Lasubine I contains three stereocenters in a quinolizidine core. Roush allylation of aldehyde 63 with provided the 1,3-aminoalcohol 67 in > 90 < 10 diastereoselectivity. Alcohol protection and alkene oxidation provided an intermediate aldehyde which underwent Roush allylation with to provide homoallylic... 

Waldmann and coworkers later developed and explored the solid-supported carbonyl allylation reactions for the stereoselective solid-phase synthesis of a collection of NP-inspired 8-lactones. To identify reaction conditions that would give rise to the allylation products with high enantioselectivity and in high yield, immobilized aldehyde 26 was synthesized as model compound and was then subjected to allylation with different chiral allylboron reagents. After some experimentation, it was found that treatment of the resin-bound aldehyde with 4 equiv of D-Ipc2BAll 28 at 78°C in THF/ether 5 1 (v/v) followed by... 

Enantioselective synthesis of homopropargyl amines can be effected through copper-catalysed reaction of an allenyl boron reagent with aldimines. The first nucleophilic allylation of r-electrophiles by allylboron reagents has been achieved enantioselectively using a chiral rhodium catalyst (Scheme an allylrhodium intermediate has been implicated. Similar additions of R CH=CR BF3K have also been reported. ... 

The tartrate ester modified allylboronates, the diisopropyl 2-allyl-l,3,2-dioxaborolane-4,5-di-carboxylates, are attractive reagents for organic synthesis owing to their ease of preparation and stability to storage71. In the best cases these reagents are about as enantioselective as the allyl(diisopinocampheyl)boranes (82-88% ee with unhindered aliphatic aldehydes), but with hindered aliphatic, aromatic, a,/l-unsaturated and many a- and /5-alkoxy-substituted aldehydes the enantioselectivity falls to 55-75% ee71a-b... 

If the presence of sensitive functional groups poses problems of chemose-lectivity in the use of hard allylic metal reagents, allylboronate derivatives also can be accessed by a milder transmetalation of allylic tin species with boron halides.This approach has been used by Corey in the synthesis of chiral bis(sulfonamido)boron reagents such as the medially 1 reagent 15 (Eq. 19) (see section Chiral Boronate Derivatives ). ... 

With the analogous reagent 125, however, the corresponding allylboronate intermediate 126 is thought to favor a transition structure 127 where the a-substituent is positioned in a pseudo-axial orientation in order to escape nonbonding interactions with the bulky tetraphenyl dioxaborolane (Eq. 99). This way, a Z-configured allylic alcohol unit of opposite configuration is obtained in diol product 128. This type of steric control with chiral a-substituted allylboronates... 

To explain the stereochemical outcome of the reaction of allylic boron reagents with carbonyl compounds, Houk and Li carried out calculations on the transition structures of the model reaction of formaldehyde and allylboronic acid6 (Scheme 3.V). The bimolecular complex formed initially between allylboronic acid and formaldehyde would rearrange via a six-membered transition state to form an intermediate. Calculations show that chair transition state A is 8.2kcal/ mol more stable than twist-boat transition structure B, clearly confirming that the six-membered chairlike transition-state model is a legitimate scheme to predict the stereochemical outcome of the boron allylation reaction. 

The chiral allyl- and 2-butenylboronates derived from tartrate esters (Chart 10-5) have been used in combination with a wide variety of chiral aldehydes to produce homoallylic alcohols in high yield and moderate to high enantioselectivity [124], The results obtained from reaction of selected chiral aldehydes (Chart 10-6) with the tartrate-modified allylboronates 195 and 197 (Chart 10-5) are shown in Table 10-20. As with the achiral aldehydes, the highest enantioselectivities are obtained when the chiral aldehydes are combined with allylboronate 197. A strong reagent-induced selectivity is apparent, but is nevertheless dependent on the intrinsic bias of the aldehyde. 

Scheme 11-10). It should be noted that glyeeraldehyde derivatives are outstanding substrates for the tartrate ester-modified allylboronates [118]. Aldehyde 261, derived from 260 in two steps, underwent a highly stereoselective (selectivity = >99 1) allylation reaction with the Brown Ipc2BAllyl reagent 195 [112, 113] (an in-depth discussion of the synthesis and use of this reagent appears in Section... 

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. 

Diastereoselective reactions of oxime (198) and phenylsulfenimines such as (201) with allyl metal reagents have been described (Scheme 33). The reaction of (198) and allylboronate (144) provides (199) with modest selectivity, while excellent diastereoselectivity was realized in the reactions of (201) and its C-2 epimer with the allylzinc reagent." The corresponding ketone derivatives, however, gave 70 30 mixtures of (204) and (205) upon reaction with diallylzinc, while with allyl Grignard, (205) is almost the exclusive product." The latter result is suggestive of a chelated transition state. 

The first examples of highly diastereoselective double asymmetric reactions involving chiral allyl metal reagents were obtained in reactions with D-glyceraldehyde acetonide (151 Table 6). Aldehyde (151) displays an 80 20 preference for (154) in reactions with the achiral pinacol allylboronate (144 entry 4),25.ioi selectivity for (154) improves to 96-98% with reagents (-)-(215) and (RJi)-... 

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... 

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