Garner aldehyde

Treatment of m-butyl (S )-4-formyl-2,2-dimethyl-3-oxazolidinccarboxylate ( Garner aldehyde, 3), readily available from /V-Boc-l-serine and configurationally extremely stable49,50, with various nucleophiles preferentially yields the n n(nonchelation)-diastereomeric amino alcohols 4 in high chemical yield51 -55,57-61. 

Scheme 7.4 (NHC)Rh-catalysed addition of phenylboronic acid to the Garner aldehyde...

Difluoromethyl proline has been prepared by a related approach. Synthesis of cis- and fra 5-4-trifluoromethyl-D-prolines has been performed starting from the Garner aldehyde. 4-Trifluoromethyl, difluoromethylene, or difluoromethyl prolines could also be prepared by 5-endo-trig cyclization of A-(homoallyl)-sulfonamides. ... 

The same group of authors has also utilized the Garner aldehyde in Biginelli reactions (Scheme 4.9), and obtained 4-oxazolidinyl-dihydropyrimidine 22 in fair... 

Scheme 4.9. Biginelli condensations with the Garner aldehyde.

The addition of phenylboronic acid to Garner aldehyde showed a high anti-selectivity, thus suggesting no chelation between the oxygen atom and rhodium metal center during the addition (Equation (223)).987 Asymmetric addition using chiral phosphine ligands was studied however, there have not yet been any practical procedures.9 ... 

One route for [2 -i- 2]-additions begins tvith a support-bound aldehyde Wills et al. [191] performed a [2 -i- 2]-cycloaddition on a support-bound second-generation Garner aldehyde (227) in order to extend its capabilities as a chiral auxiliary (Scheme 50). 

Alkynylation of Garner aldehyde F with alkyne E gave G with the required carbon skeleton. The triple bond of G was then reduced to give (Tf)-alkene H. The next epoxidation was unfortunately nonstereose-lective to give the required epoxide I and its isomer. Reduction of the epoxide I was fortunately selective with DIBAL-H as the reductant, and J was obtained after mesylation. 

A polymer-supported version of the Garner aldehyde (Scheme 12.25) was applied in the synthesis of a P-lactam [36], Owing to its strong electrophilicity the chiral, oxazolidine based Garner aldehyde is a versatile intermediate and often provides excellent asymmetric induction [37]. 

A mixture of 760 mg of phosphonium salt (0.92 mmol), 0.90 g activated 4-A powdered molecular sieves, 7.1 mL anhydrous THF, and 4.7 mL anhydrous HMPA was stirred at room temperature for 10 min and then cooled to -20°C. The stirred mixture was treated with 580 /xL 1.6 M -BuLi in hexanes (0.92 mmol), warmed to 0°C, stirred for an additional 30 min, and then cooled to -20°C. To the stirred mixture was added 336 mg Garner aldehyde in 7.1 mL anhydrous THF over a 15-min period. The mixture was allowed to reach 0°C in 2.5 h, stirred at 0°C for an additional 1 h, and then diluted with 200 mL Et20 and filtered through a pad of Celite. The ethereal solution was washed with 1 M phosphate buffer at pH 7 (3 x 30 mL), dried over Na2S04, and concentrated. The residue was eluted from a column of silica gel with 5 1 cyclohexane/EtOAc to give 457 mg 6,10-anhydro-7,8,9-tri-(9-benzyl-2-fert-butoxycarbonylamino-2,3,4,5,ll-pentadeoxy-l,2-N, 0-isopropylidene-L-f/ re(9-D-t(i(9-undec-4-(Z)-enitol as a syrup, in a yield of 75%. 

Other references related to the reactions of the Garner aldehyde are cited in the literature. 

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