Stereoselectivity proton transfer

Propynyl bromides can be enantioselectively converted to chiral allenes by stoichiometric conversion into a propynylchromium(III) complex followed by stereoselective proton transfer from a chiral auxiliary, e.g., (-)-borneol or (-)-menthol120, l2 . Formally, substitution of bromide takes place. 

Since samarium diiodide is only a one electron donor, two equivalents of the metal are required in order for the reaction to proceed. The first electron donated from the samarium produces a chiral ketyl radical 30 which undergoes enantioselective addition to the acrylate according to the chelated transition state shown in 32. The second electron donation then provides a chiral samarium enolate intermediate 33 that can potentially undergo stereoselective proton transfer in the formation of a second chiral center. 

Scheme 2.7 Stereoselective proton transfer in bent allenic intermediates 27(R) and 27(S). (Adapted with permission from Hasegawa, Y. et al., Bull. Chem. Soc. pn., 85,316-334,2012. Copyright the Chemical Society of Japan.)...

Cp2Zr(H)(Cl) (8). The apparent record for catalyzed double bond movement is on 9-decene-l-ol to decanal (nine positions) using Fe3(CO)i2 (9). However, 30 mol % was required, which means that nearly a mole of metal was used per mole of alkenol. Herein we expand upon our initial report (10) of a very active catalyst (1) which has been shown to move a double bond over 30 positions. Catalyst 1 appears to have an intriguing and useful mode of action, in which the pendant base ligand performs proton transfer on coordinated alkene and Ti-allyl intermediates in a stereoselective fashion. 

The E/Z stereoselection can be rationalized by assuming metal-centered pericyclic chairlike transition states 1 13,10 , 12 and 13. In this model proton transfer and metal ion transfer are assumed to occur simultaneously. When R is a bulky group, the nonbonded steric interaction between this group and the methyl group becomes strong and the Z-enolate will be the predominating isomer under kinetic control. 

No reactions of t with protic solvents have been reported however, its cyclic analogue 1,2-diphenylcyclobutene (7) reacts with the protic solvents methanol, acetic acid, and water, to yield adducts 85 and 86 (eq. 28). The proposed mechanism for the formation of 85 and 86 involves the formation of singlet exciplex followed by proton transfer to yield a cyclobutyl cation 87. Stereoselective nucleophilic capture of 87 by solvent from its less hindered side yields 85, while skeletal rearrangement of 87 yields the cyclopropylmethyl cation 88, which reacts with solvent to yield 86 ... 

A limiting factor is also the stereoselectivity. As the substituents a to the keto group are prone to racemization using strong Lewis or Bn /nstedt acids due to equilibria involving proton transfer, the diastereoselectivity is often low ... 

The effect of the diisopropylamine formed upon the deprotonation is again particularly important, since a complete reversal of the selectivity is observed on going from free diisopropylamine to its lithium salt or to hexamethyldisilazane. On the other hand, there is a strong dependence of the stereoselectivity of the proton transfer on both the nature of the cation and the ligands attached to the metal, though lithium iodide present with the cuprate has no noticeable effect. 

Deuteration experiments showed that the p-H atom in the product stems from borohydride whereas the a-H atom is introduced by proton transfer from ethanol. Formation of the a-(C-H) bond is nonstereoselective accordingly, the reduction of analogous substrates with an a- instead of a p-disubstituted double bond leads to racemic products (a mechanistic model rationalizing the stereoselectivity of (semicorrinato)cobalt catalysts is available ). 

Proton transfer, either intermolecular or intramolecular, can serve to stabilize 3.1. In this manner, enamines 3.4 or 3.5 can be produced as initial products (paths B and C). Production of 3.5 is particularly worrisome in stereoselective versions of the reaction with P donors because the configuration at the stereocenter derived from the prostereogenic center of the donor is established in the hydrolysis and not in the initial conjugate addition. Upon acidic hydrolysis, 3.1-3.5 all produce 3.6. 

Using the more reactive a-phenylthioacrylate as an acceptor, good selectivity for the construction of two stereogenic centers is observed (Eq. [1], Scheme 22) (47). The mechanism for the enantioselection in the establishment of the quaternary center is likely to be similar to the other examples in Scheme 22. For the formation of the thiophenyl-substituted stereocenter, intramolecular proton transfer from the immonium ion of the dipolar intermediate to the enolate is probably responsible for the stereoselection observed. 

The possibility that the stereoselectivity arises from either a thermodynamic preference or a subsequent process (cyclization) is less likely with imines as conjugate addition leads to an N-protonated immonium ion, which should rapidly undergo proton transfer. The resulting neutral product should be substantially less likely to undergo reversal to starting material than the dipolar intermediate involved in enamine Michael additions. 

If the initial addition (A, Scheme 3) is essentially irreversible, the net stereoselectivity can be controlled by interactions that exist in the transition state for the Michael addition. However, if there is not a rapid intervening process (cyclization or proton transfer), the initial dipolar adducts would be expected to reform starting materials at an appreciable rate (vide supra). Based on the reports described previously, a significant possibility exists that this initial addition is reversible, at least in most cases. If indeed step A is reversible or if the configuration of 3.1 is not stable to reaction conditions, then the net stereoselectivity can be determined by the relative stability of the dias-tereomers of 3.1 or by the relative rates of the diastereomeric transition states for some subsequent reaction (e.g., B-F).+ For example, selectivity could be induced by preferential cyclization (paths D and E) or by selective proton transfer (path B) from one of the components of the initial diastereomeric mixture (3.1). Also, it is possible that selective protonation (path F) of enamine 3.5 could give the observed products. This prospect is less likely as the generation of enamine 3.5 is disfavored by allylic strain considerations. 

Photocyclization is usually preceded by a hydrogen abstraction process, or an electron transfer-proton transfer sequence, which results in the formation of a biradical species. This reactive intermediate may then rearrange, collapse back to starting materials, or react with its surroundings, either inter- or, more usually, intramolecularly. The stereoselective photocyclization of p-aryl amines (36) to... 

The nucleophilic properties of enamines uncovered by Stork have found a wide application in Michael additions. Secondary enamines are usually in equilibrium with the corresponding imines. These imines are generally more stable, unless the tautomeric enamine is stabilized by conjugation (Figure 7.71). The primary product of the reaction of an enamine with an a,P-unsaturated carbonyl compound is a dipolar intermediate 7.108. This intermediate is converted to a 1,5-dicarbonyl compound on exposure to aqueous add. Proton transfers can take place before hydroysis to the ketone occurs, and the stereoselectivity of the process may be determined by such steps. Moreover, the enamine addition reaction can be reversible. These problems notwithstanding, the use of chiral amines to generate imines or enamines for use as Michael donors has been widely developed. The chiral imine/enamine can be preformed or, espedally in the case of intramolecular reactions, the amine can be added to the reaction medium in stoichiometric amounts. 

---