Homoenolates chiral

Keyword homoenolate, chiral, formal hydroxylation, 1-aminoallyl anions, silylation, alkylation... 

The chiral siloxycyclopropane 106 undergoes carbonylative homocoupling to form the 4-ketopimelate derivative 108 via the palladium homoenolate 107 without racemization. The reaction is catalytic in CHCI3, but stoichiometric in benzene[93]. 

Stereoselectivity of chiral homoenolate equivalents in reactions of heterocycles 99S365. 

Only few allyltitanium reagents bearing a removable chiral auxiliary at the allylic residue are known. The outstanding example is a metalated 1-alkyl-2-imidazolinone14, derived from (—)-ephedrine, representing a valuable homoenolate reagent. After deprotonation by butyllithium, metal exchange with chlorotris(diethylamino)titanium, and aldehyde or ketone addition, the homoaldol adducts are formed with 94 to 98% diastereoselectivity. 

NHC-catalysed homoenolate generation has been applied by Bode and Struble in the formal synthesis of the natural product salinosporamide A [77], The key step in the synthesis is a late-stage NHC-catalysed intramolecular lactonisation step of intermediate 186. When this reaction was attempted with an achiral triazolium-derived NHC, a 4 1 diastereomeric ratio of products was obtained in preference for the undesired product 189. In order to circumvent this, chiral triazolium salt 187 was employed, giving an approximately 1 1 mixture of desired undesired diastereoisomers (Scheme 12.41). 

Allyltitanium complexes derived from a chiral acetal have been reacted with carbonyl compounds and imines [63], While the chiral induction proved to be low with carbonyl compounds, high induction was observed with imines. This complex represents the first chiral homoenolate equivalent that reacts efficiently with imines. Finally, the reactions with electrophiles other than carbonyl compounds and imines, namely a proton source, NCS, and I2, furnished the corresponding alkene, chloro, and iodo derivatives in good yields [64]. 

An alternative formation of titanated alkoxyallenes could be achieved by reaction of 3-alkoxy-2-propyn-l-yl carbonates 78 with (r/2-propene)titanium diisopropoxylate (79). Successive addition of 80 to benzaldehyde afforded the corresponding addition products 81 in high yield (Scheme 8.22) [70]. The results demonstrate that titanium species 75 and 80 can serve as easily available ester homoenolate equivalents. Notably, conversion of lithiated alkoxyallenes to the magnesium species by treatment with MgBr2 followed by addition to chiral carbonyl compounds resulted in a mixture of a- and y-products [71]. 

If the mesomeric stabilization is provided by a double bond, the lithiated species is a homoenolate synthon, as shown in Scheme 44a. Reaction with an electrophile typically occurs at the y-position, yielding an enamine, which can then be hydrolyzed to a carbonyl compound. An important application of this approach is to incorporate a chiral auxiliary into the nitrogen substituents so as to effect an asymmetric synthesis. 2-AzaaUyl anions (Scheme 44b), which are generated by tin-lithium exchange, can be useful reagents for inter- and intramolecular cycloaddition reactions. ... 

Enders et al. 205) metalated the (S)-proline-derived chiral allylamines (209). The resulting homoenolate (210) was subsequently alkylated. Upon hydrolysis P-sub-stituted aldehydes (211) were obtained (e.e. = 64-67%). 

The optically active cyclopropane 10 gave the chiral homoenolate of isobutyrate Eq. (14), an ethereal solution of which is both chemically and configurationally stable for a week at room temperature, and consequently can serve as a useful chiral building block [23],... 

Alternatively, the ambident oi-hetero substituted allyl anions have been utilized as homoenolate equivalents. For example, in the presence of HMPA, allyl phenyl sulfides (251),192 allyl phenyl sulfones (252)192b c and allyl phenyl selenides (253)192d e add to a,(3-enones in a l,4(0)-mode, while allyl phenyl sulfoxides (254) and allyl phosphine oxides (255) afford 1 A j-addition exclusively, irrespective of solvent used.193 Hua has shown that additions of either chiral sulfoxide (254 R1 = R2 = R3 = R4 = H, R5 = p-tolyl) or allyl oxazaphospholidine oxide (256) occur with excellent enantioselectivity (>95% ee).194 Similarly, Ahlbrecht reports that the a-azaallyl (257) adds exclusively in a 1 A j-mode to acceptor (59) to afford 1,5-diketones (Scheme 86).195... 

This volume, which complements the earlier one, contains 9 chapters written by experts from 7 countries. These include a chapter on the dynamic behavior of organolithium compounds, written by one of the pioneers in the field, and a specific chapter on the structure and dynamics of chiral lithium amides in particular. The use of such amides in asymmetric synthesis is covered in another chapter, and other synthetic aspects are covered in chapters on acyllithium derivatives, on the carbolithiation reaction and on organolithi-ums as synthetic intermediates for tandem reactions. Other topics include the chemistry of ketone dilithio compounds, the chemistry of lithium enolates and homoenolates, and polycyclic and fullerene lithium carbanions. 

Metalated SMP allylamines or enamines have been used as the first chiral homoenolate equivalents (d synthons eq 5). ... 

Generation of Enantioenriched, Configurationally Stable Organolithium Reagents. (1 S,2E)-1 -(N.Af-Diisopropyl-carbamoyloxy)-l-methyl-2-butenyllithium-(—)-sparteine is configurationally stable in solution and is obtained by kinetic resolution of the racemic 2-alkenyl carbamate by n-butyllithium-(—)-sparteine with >80% de (eq 4). The enantioenriched allylstan-nane, obtained on y-stannylation, was used as chiral homoenolate reagent. The methoxycarbonylation (a, inversion) yields enantioenriched 3-alkenoates. ... 

Aldol-iype Condensation. Dimetalation of (R)-(+)-3-(p-tolylsulfinyl)propionic acid with Lithium Diisopropylamide produces a chiral homoenolate dianion equivalent which reacts with carbonyl compounds to afford p-sulfinyl-y-hydroxy acids these spontaneously cyclize to give the corresponding p-sulfinyl 7-lactones (eq 2) ... 

Several other chiral homoenolate anion equivalents have been successfully exploited for asymmetric homoaldoi reactions, e.g. (48) and (49), ° but their preparation seems more laborious than that of the carbamates (47). 

Commercially available methyl p-hydroxyisobutyrate (16) has been converted to the corresponding halide (17), then either via the silyloxycyclopropane route (A) or via the reductive route (B) to the chiral zinc homoenolate (18 Scheme 28). It is optically stable in ether and has been used for several standard carbon-carbon bond-forming reactions, e.g. carbonyl addition, arylation and acylation. ... 

An a,p-unsaturated aldehyde adds to a nitrone to give y-hydroxylaminoalkanoic ester when the substrates are exposed to an azolecarhene, and the reaction mixture is quenched by an alcohol. Homoenolate ion generated from the aldehyde and the carbene is the nucleophile. The use of carbene 109 engenders chiral products. ... 

---