Intramolecular asymmetrical

Enamines derived from ketones are allylated[79]. The intramolecular asymmetric allylation (chirality transfer) of cyclohexanone via its 5-proline ally ester enamine 120 proceeds to give o-allylcyclohexanone (121) with 98% ee[80,8l]. Low ee was observed in intermolecular allylation. Similarly, the asymmetric allylation of imines and hydrazones of aldehydes and ketones has been carried out[82]. 

Although the enantioselective intermolecular addition of aliphatic alcohols to meso-epoxides with (salen)metal systems has not been reported, intramolecular asymmetric ring-opening of meso-epoxy alcohols has been demonstrated. By use of monomeric cobalt acetate catalyst 8, several complex cyclic and bicydic products can be accessed in highly enantioenriched form from the readily available meso-epoxy alcohols (Scheme 7.17) [32]. 

The intramolecular asymmetric Stetter reaction of aliphatic aldehydes is generally more difficult to achieve due to the presence of acidic a-protons. Rovis and co-workers have demonstrated that the NHC derived from pre-catalyst 130 promotes the intramolecular Stetter cyclisation with enoate and alkyhdene malonate Michael acceptors 133. Cyclopentanones are generally accessed in excellent yields and enantioselectivities, however cyclohexanones are obtained in significantly lower yields unless very electron-deficient Michael acceptors are employed... 

Intramolecular asymmetric hydrosilylation-oxidation of (alkenyloxy) hydrosilanes provides an efficient method for the preparation of optically active polyols from al-lylic alcohols. Cyclization of silyl ethers 54 of a meso-type allyUc alcohol in the pres-... 

A new noncarbohydrate-based enantioselective approach to (—)-swainsonine was developed in which the key step was an aqueous intramolecular asymmetric hetero-Diels-Alder reaction of an acylni-troso diene (Eq. 12.57).128 Under aqueous conditions there was significant enhancement of the trans stereoselectivity relative to the reaction under conventional nonaqueous conditions. 

Yang12 has effected an intramolecular asymmetric carbonyl-ene reaction between an alkene and an a-keto ester. Reaction optimization studies were performed by changing the Lewis acid, solvent, and chiral ligand. Ligand-accelerated catalysis was observed for Sc(OTf)3, Cu(OTf)2, and Zn(OTf)2 (Equation (6)). The resulting optically active m-l-hydroxyl-2-allyl esters provide an entry into multiple natural products. 

Park et al.102 demonstrated an interesting intramolecular asymmetric allylation of imine based on a substrate-controlled mode. 

Scheme 3. Pd-catalyzed intramolecular asymmetric allylic alkylation in Genet s synthesis of chanoclavine I (1994).

A catalyst (46) that is structurally closely related to that used by Evans in his intramolecular [4+2] cycloaddition (cf Scheme 7) is utilized by Overman in an intramolecular asymmetric Cu(I)-catalyzed... 

These and other examples of intramolecular asymmetric induction by the sulfinyl group have been discussed by Montanari in his review paper (9). 

Scheme 9.21 Sequential intermolecular and intramolecular asymmetric allylic aminations.

Similarly, Takano et al. (79) reported the intramolecular, asymmetric cycloaddition of ylides derived from thermal decomposition of aziridines 255 with the stereoselectivity rationalized by the formation of a postulated nine-membered transition state 256 in which the benzyloxymethyl group was forced into an equatorial disposition. The resultant pyrrolidine 257 contained three new stereo-genic centers, each imposed with high control (Scheme 3.87). 

In addition, a proline- or phenylalanine-based Rh(II) can catalyze intramolecular asymmetric carbene reactions such as aromatic ring expansion and C—H insertion with moderate selectivity (Scheme 95) (229). Rh(II) carboxamides are also effective catalysts for asymmetric C—H or N—H insertion (228c). 

Brase reported an intramolecular asymmetric Heck-intermolecular Heck cascade reaction of l,3-bis(enolnonaflates) 131 to the highly congested bicyclic compound 132 [122] (Scheme 5). Although the level of asymmetric induction is low (up to 52% ee), this result shows that the concept of two leaving groups in the desymmetrization reaction can be applied. 

It is the intent of this chapter to outline the major synthetic developments of the intramolecular asymmetric Heck reaction as well as to examine the mechanistic factors that have been revealed to date that effect enantioselectivity. 

Further breakthroughs in enantioselectivity were achieved in the 1970s and 1980s. For example, 1971 saw the discovery of the Hajos-Parrish-Eder-Sauer-Wiechert reaction, i.e. the proline (l)-catalyzed intramolecular asymmetric aldol cyclodehydration of the achiral trione 11 to the unsaturated Wieland-Miescher ketone 12 (Scheme 1.3) [12, 13]. Ketone 12 is an important intermediate in steroid synthesis. 

Meyers, A. I. Licini, G. Intramolecular asymmetric tandem additions to chiral naphthyl 489 oxazolines. Tetrahedron Lett. 1989, 30, 4049-4052. 

An intramolecular asymmetric Michael addition of aldehydes and ketones - to give cyclopentanals - gives the otherwise disfavoured d.v-producls when catalysed with (f) antibody 38C2, the first commercially available catalytic antibody 222 One case gave 99% de, 98% ee. ... 

Scheme 4. The direct intramolecular asymmetric aldol reaction using L-proline.

In related investigations, the group of Rovis examined the effect of pre-existing stereocenters in the intramolecular asymmetric Stetter reaction [43]. The same group also exploited the concept of desymmetrization for the asymmetric synthesis of hydrobenzofuranones in an intramolecular Stetter reaction [44]. 

The use of species 118 for the umpolung of a carbonyl group, the Stetter reaction, was demonstrated for the intramolecular asymmetric conjugate addition of a formyl group to the enoate moiety of 119 to give the cyclization product 120 in high ee and yield (Scheme 15) [64]. 

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