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:

(S)-Cyclohexyl lactic acid is a component of the selective E-selectin inhibitor 2 ((S)-cHexLact-2-O-(3-Galβ(1→3)ddGlc(4→1)αFuc). We describe the evaluation of various synthetic routes to this building block:  ( A ) diazotation of phenylalanine followed by phenyl ring hydrogenation; ( B ) phenyl ring hydrogenation of phenyl alanine followed by diazotation; ( C ) acidic hydrolysis of the cyanohydrin derived from phenylacetaldehyde, enantiomeric resolution of the resulting, racemic phenyl lactic acid via diasteromeric salt formation and phenyl ring hydrogenation; ( D ) enantioselective dihydroxylation of a cinnamate ester, followed by hydrogenation of the benzylic hydroxy group and the aromatic nucleus; ( E ) enantioselective biocatalytic reduction of phenylpyruvic acid, followed by phenyl ring hydrogenation. The development of (2R)-2-O-(4-nitrophenyl)sulfonyl-cyclohexyl lactic acid p-bromobenzylester 21 as a buidling block with improved crystallinity and stability is also described.

Die enantioselektive Umwandlung vieler Aldehyde in tert‐Butylester von 3‐Hydroxycarbonsäuren 2 gelingt mit dem Titanreagens 1 (R* siehe vorstehenden Beitrag). Acetatenolate konnten früher nicht direkt verwendet werden. Erstaunlicherweise ist diese Aldol‐Reaktion kaum temperaturabhängig, so daß auch bei Raumtemperatur eine hohe Induktion resultiert. Die Reagentien (CpTiCl3 und R*OH) lassen sich zurückgewinnen.