Allyl carbamates homoaldol reaction

Lithiated allylic carbamates (35) (prepared as shown) react with aldehydes or ketones (R C0R ), in a reaction accompanied by an allylic rearrangement, to give (after hydrolysis) y-hydroxy aldehydes or ketones. The reaction is called the homoaldol reaction, since the product is a homolog of the product... 

Titanated allyl carbamates are reported to react regio- and stereospecifically with aldehydes [52]. An elegant and synthetically useful method based on diastereoselective and en-antioselective homoaldol reactions has been developed (Scheme 13.25) [53]. 

Scheme 13.25. Diastereoselective and enantioselective homoaldol reactions using titanated allyl carbamates.

SCHEME 24. (-)-Sparteine-induced deprotonation of allyl carbamate 170. Dynamic resolution by crystallization and enantioselective homoaldol reaction... 

The 2-butenyltitanium reagents are generated by the deprotonation of an E-2-butenylcarbamate 279 with n-butyllithium and then reaction of the newly formed allylic lithium species 280 with chlorotris(diethylamino)titanium [179]. The 2-bu-tenyltitanium reagent 281 is then combined with aldehydes to produce homoallylic alcohols 282 in high yield and excellent regioselectivity (Scheme 10-93). The enol carbamate moiety is readily converted to a carbonyl group and thus constitutes a homoaldol reaction. 

The most sophisticated homoenolate equivalents, and the first to allow some control over stereochemistry, are the lithium derivatives 160 of allyl carbamates 159 introduced by Hoppe.1 They are particularly valuable for reaction with an aldehyde or a ketone in a homoaldol reaction. 

Enantioselective homoaldol reaction induced by sparteine and Ti catalyzed, also asymmetric deprotonation of allyl carbamates. 

The addition of heteroatom-substituted allylic anions to aldehydes has found particular interest as it represents a homoaldol reaction. Metalated allyl carbamates seem to be the most valuable reagents developed for this purpose as they are prepared easily and exhibit high y-selectivity and dia-stereoselectivity, at best in their titanated form (Scheme 79). 

The titanium- ate complexes of a-methoxy allylic phosphine oxides, generated in situ by reaction of the corresponding lithium anion and Ti(0-i-Pr)4, condense with aldehydes exclusively at the a-position to produce homoallylic alcohols in a diastereose-lective fashion. The overall result is the three-carbon homologation of the original aldehyde, and this protocol has been used in a synthesis of (-)-aplysin-20 from nerolidol. The titanium- ate complex produced by reaction of the chiral lithium anion of an ( )-crotyl carbamate with Ti(0- -Pr)4 affords -y-condensation products (homoaldols) on reaction with aldehydes. Allyl anions produced by the reductive metalation of allyl phenyl sulfides condense with a,p-unsaturated aldehydes in a 1,2-manner at the more substituted (a) allyl terminus in the presence of Ti(0-i-Pr)4. 1,2-Addition of dialky Izincs to a,p-unsaturated aldehydes can be achieved with useful levels of enantiocontrol when the reaction is conducted using a chiral titanium(IV) catalyst in the presence of Ti(0- -Pr)4 (eq 20). Higher ee values are observed when an a-substituent (e.g. bromine) is attached to the substrate aldehyde, but a -substituent cis-related to the carbonyl group has the opposite effect. 

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