Enantioselective Aldol Reaction of tert‐Butyl Acetate using Titanium‐Carbohydrate Complexes

Abstract

R 2 d -7 8 % R l T 6 a , R ' = lsobutyl ?a, R Z -Vinyl 8 a , 6 8 % (90% e e ) 8b, 59% ( 8 8 % ee j 6a, R ' = lsobutyl 6b, R ' = lsopropyl 7c, R 2 = CH, 8c, 4 6 % ( 8 3 % e e ) 7b, R Z = C,H, EH, CH, 10 (56.6%) 1 1 ( 0 . 7 % ) 12 ( 1 9 . 4 % ) 13 ( 3 . 3 % ) Scheme 2.With the chiral reagents 3 and 7a-c the enantioselective allylation of aldehydes has been achieved for the first time with organotitanium compounds. Boron reagentsI2' exhibit a similar stereoselectivity, but the advantage of titanium must not be overlooked, e.g. simple preparation, chemoselectivity, inexpensive auxiliaries, as well as the possibility of recovering diisopropylideneglucose and CpTiCI, 1. Still a drawback of this method is, however, that the high price of L-glucose impedes an equally good access to the other enantiomers of the homoally1 alcohols 4. Concerted efforts are therefore currently directed a t solving this problem with other ligands. E.uperirnen tnlStock solution of 2 in ether: A solution/suspension of 1 (11.0g. 50mmol. freshly i n Et,O (400 mL. distilled over Naihenzophenone) was treated with 26.0 g (0.1 mol) of 1.2: 5,6-di-O-isopropylidene-a-o-glucofuranose (R*OH, crystallized from cyclohexane) under argon in the absence of moisture. After 2 min at room temperature (RT) a solution of 15.2mL (ll0mmol) of Et,N in 125 m L of Et,O was added dropwise to the stirred mixture within 1 h. The resulting suspension was stirred for ca. 15 h; the Et,N. HCI was then filtered off under argon and washed three times with ca. 50 mL of Et,O (14 2 g o f E t , N . HCIvacuumdried).ThecontentofZin theyellowfiltrate(0.09 was calculated from the volume of the solution assuming a quantitative conversion. (R)-l-Phenyl-3-huten-l-ol(4a): 7.2 mL of a 1.25 M solution of allylmagnesium chloride in T H F (Aldrich, 9 mmol) was added dropwise within 10 min at O'C under argon to 110 mL of a ca. 0.09 M solution of 2 in Et,O (9.9 mmol). After stirring for 1 h at 0 C the orange suspension was cooled to -74 C and treated within 5 niin with 0.8 mL (8 mmol) of henzaldehyde. The mixture was stirred for 2 h at -74 C . warmed to ca. -3 0 ' C and hydrolyzed by addition of 16 mL of a ca. 5 M solution of H,O in T H F (1 h, RT). Filtration, washing with Et,O and drying (high vacuum) yielded 4.2 g of 5 (yellowish solid). The filtrate was evaporated and the solid residue stirred with 100 mL of hexane. Subsequent filtration furnished 4.4 g of R*OH. Chromatography (80 g silica gel, hexane: AcOEt 3.1) finally afforded 1.01 g (85%) of 4a (90% w, determined as described in (121). Received: December 21. 1Y88 [Z 3095 IE] German version:

Subtle Variations in the Long-Range Transmission of Stereochemical Information: Matched and Mismatched Aldol Reactions

“…The b-hydroxy tert-butyl ester 12 was prepared with high enantioselectivity by the reaction of aldehyde 11 with lithio tert-butyl acetate following precedents and protocols described by Duthaler and co-workers in other contexts (Scheme 2). [10] With the expectation of probing the basis of Schinzer et als findings in greater detail, we also prepared the ent b-hydroxyester 13 and converted the enantiomeric C3 alcohols into their TBS derivatives 14 and 15. However, we were unable to effect aldol condensation between 6 and the lithio enolates derived from 12 or 13 owing to vulnerabilities in the b-siloxyester network.…”

“…[10] Correlations started with condensation of lithio-20 with 6 to afford the C6(R),C7(S) and C6(S),C7(R) aldol products in a 4:1 ratio. Protection of each compound as the Troc derivative and deprotection of the aldehyde function afforded compounds 21 and 22.…”

Titanium-catalyzed Reformatsky-type reaction

“…The three titanium complexes are quite different in terms of coordination properties. The titanium enolates prepared by transmetallation from the Duthaler-Hafner reagent afford good facial selectivity with aldehydes in diethyl ether as the reaction solvent [31]. Quite interestingly, the stereoselection was independent by the reaction temperature in the limit of the isobutyraldehyde investigated.…”

Subtle Variations in the Long-Range Transmission of Stereochemical Information: Matched and Mismatched Aldol Reactions

“…[13] L. J. Mathias, Synthesis 1979, 11, 561 ± 576. [10] With the expectation of probing the basis of Schinzer et als findings in greater detail, we also prepared the ent b-hydroxyester 13 and converted the enantiomeric C3 alcohols into their TBS derivatives 14 and 15. [15] was not established.…”

“…[10] Correlations started with condensation of lithio-20 with 6 to afford the C6(R),C7(S) and C6(S),C7(R) aldol products in a 4:1 ratio. [10] Correlations started with condensation of lithio-20 with 6 to afford the C6(R),C7(S) and C6(S),C7(R) aldol products in a 4:1 ratio.…”