S- -2-methoxymethyl pyrrolidine

Progress has been made toward enantioselective and highly regioselective Michael type alkylations of 2-cyclohexen-l -one using alkylcuprates with chiral auxiliary ligands, e. g., anions of either enantiomer of N-[2-(dimethylamino)ethyl]ephedrine (E. J. Corey, 1986), of (S)-2-(methoxymethyl)pyrrolidine (from L-proline R. K. EHeter, 1987) or of chiramt (= (R,R)-N-(l-phenylethyl)-7-[(l-phenylethyl)iinino]-l,3,5-cycloheptatrien-l-amine, a chiral aminotro-ponimine G. M. Villacorta, 1988). Enantioselectivities of up to 95% have been reported. 

The Michael additions of chiral cycloalkanone imines or enamines, derived from (FV l-l-phcnyl-ethanamine or (5)-2-(methoxymethyl)pyrrolidine, are highly diastereofacially selective reactions providing excellent routes to 2-substituted cycloalkanones. This is illustrated by the addition of the enamine of (S)-2-(methoxymethyl)pyrrolidine and cyclohexanone to 2-(aryl-methylene)-l,3-propanedioates to give, after hydrolysis, the (2 5,a.S )-oxodicstcrs in 35-76% yield with d.r. (2 S,aS)/(2 S,a/ ) 94 6- > 97 3 and 80-95% ee214. 

In a related study, the reaction of the enamine, l,2-dihydro-3-(2-methoxymethyl-l-pyrrolidin-yl)naphthalene [from 3,4-dihydro-2(l//)-naphthalenonc and (S)-2-(methoxymethyl)pyrrolidine] with 2-aryl-l-nitroethenes gave, after hydrolysis, an 83 17 to 95 5 mixture of the (3S,YR)- and (1/ ,1 T )-nitro ketones31. 

The resulting (S)-2-(methoxymethyl)pyrrolidine can be recovered and converted to the chiral auxiliary (see the Appendix). 

Nitromethyl-l-oxo-cycloalkane bzw. 1-Nitromethyl-cycloalkene lassen sich mit Pyrro-lidinen oder (S,)-2-Methoxymethyl-pyrrolidin bzw. -piperidin in Acetonitril bei 20° unter Austausch der Nitro-Gruppe in guten Ausbeuten in 2-(Pyrrolidino-methyl)-l-oxo-cycloalkane3 bzw. l-(Piperidino-methyl)-cycloalkene8 uberfuhren (s.a. S. 378) ... 

The ability of DAST (1) to replace hydroxy groups of alcohols with fluorine was discovered by Middleton.37 Many dialkylaminosulfur trifluorides, differing from DAST (1) only by the amino substituent, as well as bis(dialkylamino)sulfur difluorides have been prepared (for a recent review, see ref 38). but none has become as popular as DAST, This is due to the fact that DAST was the first to be commercially available, although its high cost may be prohibitive for industrial applications in most cases. Recently, a homochiral aminofluoro-24-sulfane, [(S)-2-(methoxymethyl)pyrrolidin-l-yl]sulfur trifluoride, was synthesized.39 In the reaction of this DAST analog with racemic silylated alcohols, only low to moderate enantiomeric excesses of fluorinated products have been observed.39... 

Enders, D. Klatt, M. Asymmetric Synthesis with (S)-2-Methoxymethyl Pyrrolidine (SMP)-A Pioneer Auxiliary, Synthesis 1996, 1403-1418. 

A chiral analog of DAST, (S)-2-(methoxymethyl)pyrrolidin-l-ylsulfur trifluoride [131], was prepared and studied to achieve enantioselection in the fluorination of chiral alcohols by double stereodifferentiation (Scheme 2.60). The desired effect was observed, but not to a preparatively useful extent. 

Methylenecyclohexenones.1 A diastcrcosclective synthesis of a 2-me.hylene-cyclohcxcnonc (5) involves use of (S)-2-(methoxymethyl)pyrrolidine (1) as the chiral auxiliary and as the leaving group for generation o t e eYo-methylcnc group. 

Furthermore, asymmetric dimerization is also examined by introducing either a chiral auxiliary to the nucleophile or a chiral ligand to the palladium catalyst. Diastereoselective dimerization of butadiene with the chiral enamine 18 followed by hydrolysis gave optically active 2-(2,7-octadienyl)cyclohexanone 19 with 72% ee, although the chemical yield was not mentioned in the literature." In this case, (S)-(-)-2-(methoxymethyl)pyrrolidine 20 used as a chiral auxiliary can be recovered (Scheme 5). 

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