Allylmetal chiral

Enantioselective carbonyl allylation is one of the most broadly utilized transformations in synthetic organic chemistry (For reviews on enantioselective carbonyl allylation, see [199-204]). Shortly after the first reports of carbonyl allylation employing isolable aUylboron and allylsUicon reagents by Mikhailov and Bubnov [205] and Hosomi and Sakurai [206], respectively, enantioselective carbonyl allylations were reported by Hoffmann (see footnote 19, [207]). While the design of increasingly effective chiral allylmetal reagents continues 207-220], this... 

Fig. 2 Selected examples of chiral allylmetal reagents for enantioselective carbonyl allylation...

Addition of organometallic reagents to imines is not limited to allylmetal derivatives. Hoveyda and Snapper have demonstrated that dialkylzinc reagents can add to imines in a one-pot procedure. Using a zirconium complex as metal catalyst and a chiral peptide, diverse enantioenriched aryl, aliphatic and alkynyl amines 142 have been obtained with high levels of enantioselectivity (Scheme 8.60) [136],... 

The chemistry of asymmetric allylation of carbonyl compounds has further progressed since the review in Comprehensive Asymmetric Catalysis [1] and plenty of papers including reviews [2,3] on chiral catalysts for the reaction have since appeared. This chapter describes new examples of catalytic enantioselec-tive allylation of carbonyl compounds with allylmetals in the presence of a catalytic amount of chiral Lewis acid or chiral Lewis base (Scheme 1). Compounds 1-36 [4-49] shown in Fig. 1 are the chiral catalysts reported since 1998, which have been used in the asymmetric allylation or propargylation of carbonyl compounds. Chiral compounds 37-40 [50-53], which have been utilized in the stoichiometric version, are also candidates for the chiral catalyst (Fig. 2). 

Catalytic asymmetric allylations of aldehydes or ketones are roughly classified into two methods, namely, those using chiral Lewis acid catalysts and those using chiral Lewis base catalysts. The former method uses less reactive allylsilanes or allylstannanes as the allyl source. The latter method requires allyltrichlorosi-lane or more reactive allylmetals. Both processes are applicable to the reactions with substituted allylmetal compounds or propargylation. 

Asymmetric allylation is a valuable method for constructing chiral functionalized structures, and many chiral allylmetal reagents directed toward a high level of asymmetric induction have, therefore, been designed and synthesized. Although for some of these good to excellent enantio- and diastereoselectivity are obtained in reactions with achiral aldehydes, we developed the first novel method for a catalytic process in 1991 [49a]. 

The catalyzed hydrocyana a stable (salen)aluminum c BUjSnCN. It is important to An asymmetric synthesi A -(benzyloxyiminoacety 1 )-bi Mo(CO) and LiOH sequenti Addition of allylmetals t directly attached to the yyn-chlorohydrins and anti-via two oxygen atoms and th useful for the synthesis of < en-4-ols, respectively. (-)-Sx A chiral reagent derived f tartrate reacts with aromahe alcohols sometimes in excel been conducted in the presei. Allylsilanes modified by a tai... 

Finally, the allylmetal aldehyde addition can also operate under the influence of stereocontrolling reagents, in particular, chiral Lewis acids and related activators (Eq. (10.6)). In these cases the stereochemical influence on the steric course of the reaction is due to a non-covalently bound agent that is found in neither the educts or products. Thus, the term external stereoselection will be used to describe the enantiofacial outcome at the newly formed stereogenic centers. 

Reactions of Achiral Type I and Type III Allylmetal Reagents with Chiral Aldehydes... 

In the reactions of Type II allylmetal reagents with chiral aldehydes, y -alkoxy substituents on the aldehyde can exert a strong influence on the reaction, much more so than in reactions of Type I allylmetal reagents. Reetz and co-workers reported that the BF3-OEt2-catalyzed allylation reaction of the /f-benzyloxy aldehyde 130 with allyltrimethylsilane 131 is selective for the, 3-anti diol 132 (Eq. (11.7)) [92]. Evans and co-workers sub.sequently rationalized this result by invoking tran-... 

In the following Sections we review the reactions of chiral allylmetal and allenylmetal reagents and their application to the synthesis of complex natural products. These reagents are useful for the enantioselective allylation of achiral aldehydes... 

The allylation reactions of carbonyl compounds catalyzed by chiral Lewis acids represent a powerful new direction in allylmetal chemistry. Yamamoto and coworkers reported the first example of the catalytic enantioselective allylation reaction in 1991, using the chiral (acyloxy)borane (CAB) catalyst system (see below) [288]. Since then, several additional reports of the catalytic allylation reaction have appeared. To date, the most effective catalyst systems reported for the enantioselective reaction of aldehydes and Type II allyl- and crotylstannane and silane reagents include the Yamamoto CAB catalyst and catalysts complexes composed of various Lewis acidic metals and either the BINOL or BINAP chiral ligands [289-293]. Marshall and Cozzi have recently reviewed progress in the enantioselective catalytic allylation reaction [294, 295]. 

The activation of the carbonyl group by Lewis acids was another leap made in the 1960s as typified by Mukaiyama-aldol reaction. In sharp contrast to the conventional carbonyl addition reactions that had been run under basic conditions, this new method allowed the addition of various nucleophiles under acidic conditions with high chemo- and stereocontrol and, consequently, the scope of the carbonyl addition reaction was extensively expanded. The Lewis acid-promoted ally-lation with allylmetals and ene reaction also received as much attention as the aldol-type reaction. It should be further pointed out that the catalytic versions of asymmetric reactions, which represent one of the most exciting topics in recent synthetic chemistry, owe their development strongly to the Lewis acid activation protocol. The design of a variety of chiral ligands for metals has produced luxuriant fruits in this field. 

Asymmetric allyation of carbonyl compounds to prepare optically active secondary homoallyhc alcohols is a useful synthetic method since the products are easily transformed into optically active 3-hydroxy carbonyl compounds and various other chiral compounds (Scheme 1). Numerous successful means of the reaction using a stoichiometric amount of chiral Lewis acids or chiral allylmetal reagents have been developed and applied to organic synthesis however, there are few methods available for a catalytic process. Several reviews of asymmetric allylation have been pubHshed [ 1,2,3,4,5] and the most recent [5] describes the work up to 1995. This chapter is focussed on enantioselective allylation of carbonyl compounds with allylmetals under the influence of a catalytic amount of chiral Lewis acids or chiral Lewis bases. Compounds 1 to 19 [6,7,8,9,10,11,12,... 

Catalytic enantioselective allylations of aldehydes already published can be classified into two methods carried out under the influence of chiral Lewis acid catalysts and chiral Lewis base catalysts. The process by chiral Lewis acid catalysts generally uses allyltrimethylsilane or allyltrialkylstannane as an allylating agent, both of which show low reactivity toward aldehydes without these catalysts. The process by chiral Lewis base catalysts employs allyltrichlorosilane or allylmetals possessing relatively higher reactivity. Both processes can be successfully applied to various substituted allylmetal compounds or allenylmetal compounds. 

A few examples of stereoselective additions of organomagnesium or -cerium reagents to imines bearing a chiral arenechromium tricarbonyl or dieneiron tricarbonyl residue have been described [539, 1197], Reactions of allylmetals with an oxime bearing a chiral ether functionality can be stereoselective provided that the oxime displays the E configuration [1198],... 

Under Lewis add catalysis, the reaction of allylsilanes takes place easily with a-enones but not with a,P-unsaturated esters [162]. Because disappointing results were obtained in reactions of allylmetals with a,P-unsaturated carbonyl compounds, reactions of allylsilanes with electrophiles bearing chiral auxiliaries have been examined. Schultz and Lee [1435] performed the T1CI4 catalyzed addition of trimethylallylsilane to compound 7.67 at -78°C. After treatment with methylhy-droxylamine in acidic media, the 1,4-adduct 7.80 was obtained with high ee (Figure 7.56). Under similar conditions, N-enoyloxazolidinone 7.68 (R = Ph) or sultam... 

Alternatively, a diastereocontroUed formation of quaternary centers could be achieved by the use of an enantiomericaUy pure electrophile with a stereodefined allylmetal species [108]. In this case, a preassociation of the metal with polarized functional groups is supposed to influence the stereochemical outcome. Thus, the stereocontrolled carbocupration of unfunctionalized alkynes followed by homologation and reaction with chiral sulfinyUmines resulted in diastereomerically pure adducts 374 that can be easily deprotected to provide enantiomericaUy enriched homoallylic primary amines possessing an all-carbon quaternary stereocenter (Scheme 10.128). 

Table 9.6 Reaction of chiral iminoesters with allylic organometallic compoimds [19] Allylmetal...

If the presence of sensitive functional groups poses problems of chemoselectivity in the use of hard allylmetal reagents, allylboronate derivatives can also be accessed by transmetallation of allyltin species with boron halides [29], This approach was used by Corey in the synthesis of chiral bis(sulfonamido)boron reagents (Section 6.3.1.3) [30]. Recently, Williams and co-workers employed this mild approach to synthesize the highly functionalized allylboron reagent 9, which was employed in a key aldehyde allylboration reaction en route to the total synthesis of leucasdandrolide A (Equation 5) [31]. 

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