Asymmetric crotylation reactions

The allylation reaction between ketones and allylsilanes was achieved in 2005. Yamamoto and Wadamoto developed the asymmetric allylation reaction in the presence of AgF-Difluorphos (Scheme 9.6).12 The reaction of ketones and allyltrimethoxysilane in the presence of AgF and Difluorophos afforded the corresponding tertiary homoallyhc alcohols with high enantioselectivities. Additionally, a,(3-unsaturated ketones could be used as substrates, and this catalytic system could be applied for the asymmetric crotylation reaction to obtain anti adducts preferentially (Schemes 9.7 and 9.8). When a,p-unsaturated ketones were used as substrates, 1,2-addition products were obtained exclusively. As described before, the anti adducts were obtained predominately, regardless of the geometry of crotyltrimethoxysilane. 

Hu, T., Takenaka, N., Panek, J. S. Asymmetric Crotylation Reactions in Synthesis of Polypropionate-Derived Macrolides Application to Total Synthesis of Oleandolide. J. Am. Chem. Soc. 2002,124,12806-12815. 

The synthesis of the 368 began with the asymmetric crotylation reaction of (5)-217a with aldehyde 369 in the presence of TMSOBn and TMSOTf (Scheme 11-23). Adduct 370 was converted to the syn a-methyl-/(-benzyloxy aldehyde 371,... 

Eqs. (11.48) and (11.49)) [310]. While adduct ent-l06c, obtained with 98 2 diastereo-selectivity, results from the matched crotylation of ent-91c with crotyl-stannane 10, the anti,syn adduct 107c, obtained in 90 10 selectivity, is the result of a mismatched double asymmetric crotylation reaction. However, with these aldehydes, a stoichiometric amount of the CAB catalyst is necessary for synthetic efficiency. 

In the first step, reagent 7, developed by Hoffmann, is used lor asymmetric crotylation in order selectively to create the stereogcnic centers at C-10 and C-ll (dr >98 2).13 14 This produces compound 24, which is subsequently protected at C-11 as the p-mclh-oxyben/yl ether Protection is accomplished by reaction of the anion of the alcohol with commercially available p-methoxyben/yl chloride.15 16... 

Asymmetric allylation and crotylation reactions using allylic trichlorosilanes and chiral phosphonamides were developed by Denmark and coworkers in 1994 and further refinement of the chiral ligands system was made in 200114 (Scheme 3.2k). The influence of the six-membered chairlike transition state is once again evidenced by the excellent correlation of the geometry of the reacting silanes with the diastereomeric composition of the products. Thus, anti -isomer is obtained from the -allylic silane, and syn-isomer is produced from the Z-silane. Based on... 

Asymmetric Pericyclic Reactions. Several reports illustrate the utility of fra/is-2,5-dimethylpyirolidine as a chiral auxiliary in asymmetric Claisen-type rearrangements, [4 + 2], and [2 + 2] cycloaddition reactions. The enantioselective Claisen-type rearrangement of N,0-ketene acetals derived from tram-2,5-dimethylpyrrolidine has been studied. For example, the rearrangement of the iV.O-ketene acetal, formed in situ by the reaction of A-propionyl-fra/w-(25,55)-dimethylpyrrolidine with ( )-crotyl alcohol, affords the [3,3]-rearrangement product in 50% yield and 10 1 diastereoselectivity (eq 9). 

Solid-supported synthesis has rapidly emerged as an important strategy in synthetic organic chemistry. Solid-phase methodology is aimed at the direct synthesis of libraries of molecularly diverse compounds for biological evaluation in lead discovery. The asymmetric addition of polymer-supported chiral crotylsilanes to acetals and allylation of polymer-bound acetals linked through an ester with the chiral crotylsilanes has been investigated [44d] la can be employed in these crotylation reactions and results in the formation of polymer-supported homoallylic esters with diastereoselec-tivity similar to that of solution-phase reactions. 

A synthesis of both the polypropionate and spiroacetal fragments of rutamycin B have been described by Panek and Jain [65]. The majority of stereocenters were introduced via asymmetric allylation and crotylation reactions however, an aldol... 

Marshall subsequently demonstrated that the efficiency of the crotylation reactions catalyzed by CAB catalyst 459b could be improved by using the more reactive crotylstannanes and employing two equivalents of (CF3C0)20 to aid catalyst turnover [310]. In a comparative study of the catalytic asymmetric allylation and crotylation reactions of cyclohexane carboxaldehyde with allyl- and crotylstannanes 98 and 10, Marshall demonstrated the complementarity between the BINOL-Ti(0-i-Pr)4 catalyst 451 and the CAB catalyst 459b (Table 11-29). 

The Brown asymmetric crotylation is a highly regioselective and stereospecific reaction. Many organoboranes are now commercial available. Reviews (a) Denmark, S. E. Alrnstcad, N. G. In Modem Carbonyl Chemistry, Otera, J, Ed. Wiley-VCH Weinheim, 2000 Chapter 10 Allylation of Carbonyls Methodology and Stereochemistry,... 

Finally, Maikov and coworkers used terpene-derived IV,IV -dioxide 21.22 in a total synthesis of marine serrulatane diterpene (—)-elisabethadione 21.67 (Scheme 21.9) exhibiting potent anti-inflammatory activity. Asymmetric crotylation of cinnamaldehyde 21.65 on a 5 mmol scale afforded syn-homoallylic alcohol 21.66 in 82% yield, 94% enantiomeric excess and with complete distereoselectivity. Other key reactions to install the stereogenic centres of the target molecule included anionic ory-Cope rearrangement and cationic cyclisation. ... 

The synthesis of 252 began with Brown s asymmetric crotylation to aldehyde 261. The resulting homoallyl alcohol was converted benzyl ester 262, which was reduced to give lactol acetate 263. Axial allylation to 263 formed 2,6-trans-tetrahydropyran 264, which was subjected to ozonolysis to give an aldehyde. Addition of alkenylzinc, prepared by hydrozircona-tion of an alkyne 265, to the aldehyde mediated by chiral ligand 266 yielded allyl alcohol 267 with a 5.1 1 diastereoselectivity [110]. The stereochemistry of the major isomer was found, unexpectedly, to be the S-form at Cl7, which rendered the macrolactonization to adopt the Mitsunobu reaction. The iodide 252, prepared from 267 in three steps, reacted with... 

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. 

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]. 

Alcohol 52 was prepared by asymmetric crotylation of 2-benzyloxyac-etaldehde with the crotyl derivative of 53. What is the structure of this reagent. Provide a mechanistic rationale for the diastereoselectivity of the following reaction (the product is a racemic mixture). (Lasonolide-7)... 

Hoffmann has investigated a fundamentally different approach for enan-tioselective allylation [56] and crotylation [57-60] in which the stereogenic center that dictates the stereochemical outcome of the reaction resides within the allyl fragment. Thus, asymmetric crotylations with the chiral chloro-substituted ( )-crotyl reagent 46 typically exceed 90% ee (Scheme... 

It has been demonstrated by Pancrazi, Ardisson and coworkers that an efficient kinetic resolution takes place when an excess (2 equivalents) of the racemic titanated alkenyl carbamate rac-334a (R = Me) is allowed to react with the enantiopure )-hydroxyaldehyde 341 or alternatively the corresponding y-lactol 340, since the mismatched pair contributes to a lower extent to the product ratio (equation 91) . Under best conditions, the ratio of the enantiomerically pure diastereomers 3,4-anti-4,5-syn (342) and 3,4-anti-4,5-anti (343) is close to 14 1. Surprisingly, approximately 9% of the iyw,iyw-diastereomer 344 resulted when the starting (ii)-crotyl carbamate was contaminated by the (Z)-isomer. The reasons which apply here are unknown. Extra base has to be used in order to neutrafize the free hydroxy group. The pure awft, awfi-product 345 was obtained with 85% yield from the reaction of the (W-oxy-substituted titanate rac-334b and lactol 340. 345 is an intermediate in the asymmetric synthesis of tylosine . ... 

An additional issue of regiocontrol arises in asymmetric induction when the n-allyl complex possesses a primary terminus. Although steric factors favor the formation of the achiral linear product, alkylations with reactive nucleophiles often benefit from electronic effects leading to the branched product [ 147,148]. Of particular interest is the reaction of the crotyl system because... 

Homoallylic alcohols (8, 111-112). The high rltreo-selectivity observed in the reaction of benzaldehyde with crotyl bromide (either irons or cis) is general for relatively unhindered aldehydes (equation I). High threo selectivity is still observed in the reaction with an a-methyl substituted aldehyde, but a-asymmetric induction (at C3) is rather low (2.2 1) with simple aldehydes (equation II).1... 

A crotyl group is added to the aldehyde in an asymmetric reaction. 

Several methods promoted by a stoichiometric amount of chiral Lewis acid 38 [51] or chiral Lewis bases 39 [52, 53] and 40 [53] have been developed for enantioselective indium-mediated allylation of aldehydes and ketones by the Loh group. A combination of a chiral trimethylsilyl ether derived from norpseu-doephedrine and allyltrimethylsilane is also convenient for synthesis of enan-tiopure homoallylic alcohols from ketones [54,55]. Asymmetric carbonyl addition by chirally modified allylic metal reagents, to which chiral auxiliaries are covalently bonded, is also an efficient method to obtain enantiomerically enriched homoallylic alcohols and various excellent chiral allylating agents have been developed for example, (lS,2S)-pseudoephedrine- and (lF,2F)-cyclohex-ane-1,2-diamine-derived allylsilanes [56], polymer-supported chiral allylboron reagents [57], and a bisoxazoline-modified chiral allylzinc reagent [58]. An al-lyl transfer reaction from a chiral crotyl donor opened a way to highly enantioselective and a-selective crotylation of aldehydes [59-62]. Enzymatic routes to enantioselective allylation of carbonyl compounds have still not appeared. 

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