Mannich vinylogous

Triisopropylsilyloxyfurans were effective nucleophiles for the vinylogous Mannich addition to iminium ions that were formed by Rh2(cap)4-catalyzed oxidation of N-alkyl groups by THYDRO <06JA5648>. A stereoselective addition of 2-trimethylsilyloxyfurans to aryl aldehydes-derived aldimines employing a chiral phosphine/Ag complex as catalyst was developed <06AG(I)7230>. The prototypical example is shown below. 

Addition of carbon nucleophiles to furfural tosylhydrazone provides 5-substituted 2E,4E-pentadienyls in good yields <00TL2667>. The ab initio calculations at the RHF/3-21G level have been utilized to study the origins of diastereoselectivity of the vinylogous Mannich reaction of 2-methylfuran with pyrrolinium ion . A simple procedure for isomerization of 2-furylcarbinols to cyclopentenones under neutral condition was reported and a new mechanism was proposed <00H(52)185>. 

For vinylogous Mannich reactions see Arend M, Westermann B, Risch N (1998) Angew Chem Int Ed 37 1044... 

Scheme 26 Vinylogous Mannich reaction of 2-(trimethylsiloxy)furan...

The Schneider group independently reported an asymmetric vinylogous Mannich reaction (Scheme 27) [47]. Addition of silyl dienolates 73 to A-PMP-protected imines 74 was promoted by phosphoric acid (R)-3g (5 mol%, R = Mes) with mesityl substituents to afford tra i -a,p-nnsatnrated 8-amino esters 75 in high yields (66-94%) together with good enantioselectivities (80-92% ee). 

Scheme 27 Vinylogous Mannich reaction of silyl dienolates 2.3.5 Aza-Ene-Type Reaction...

Scheme 6.78 Typical products of the vinylogous Mannich addition of a,a-dicyanoalkenes to N-Boc-protected aldimines catalyzed by 63.

A similar vinylogous Mannich reaction has been used by Martin in the total syntheses of the heteroyohimboid alkaloids (—)-ajmalicine and (—)-tetrahydroalstonine <1995JOC3236>. An attempted synthesis of an opioid analgesic 2,4-dibenzyl-3,7-diazabicyclo[3.3.1]nonan-9-one-l,5-dicarboxylate (piperidone) by a double Mannich reaction of oxoglutarate, 2 equiv of phenylacetaldehyde, and methylamine did not give the expected product but instead gave rise to an unexpected [l,6]naphthyridine derivative (Scheme 57) <1998PHA442>. 

A preparation of yohimbenone [152] by closure of the D-ring with formaldehyde can be considered as a vinylogous Mannich reaction. 

The vinylogous Mannich reaction of triisopyloxyfurans with aldimines prepared from aldehydes and 2-aminophenol proceeded with moderate selectivity in the presence of a catalytic amount of a Ti(IV)-BINOL complex [22]. 

Scheme 9.18. Vinylogous Mannich reaction with silyloxyfurans.

Under similar conditions, the same authors were able to control two stereogenic centers in an asymmetric vinylogous Mannich reaction. Indeed, treatment of imines derived from aryl a-ketoesters with siloxyfuran under related conditions gave functionalized y-butenolides with high diastereo- and enantioselectivities (Scheme 10.21 ).40... 

S. K. Bur, S. F. Martin, Vinylogous Mannich Reactions Selectivity and Synthetic Utility, Tetrahedron 2001, 57, 3221-3242. 

Liras, S., Lynch, C.L., Fryer, A.M., Vu, B.T. and Martin, S.F. (2001) Applications of vinylogous Mannich reactions, total synthesis of the ergot alkaloids rugulovasines A and B and setoclavine. Journal of the American Chemical Society, 123, 5918-5924. 

The synthetic utility of vinylogous Mannich additions of 2-silyloxyfurans to cyclic iminum ions <2001T3221> that provided threo- mAucts predominantly was demonstrated by the assembly of the complete carbon framework during the total synthesis of the plant alkaloid, crommine, as shown in Scheme 11 <1996JA3299, 1999JA6990>. 

Inversely, vinylogous Mannich bases give the adducts 334 by reaction with dieno-philes such as maleic anhydride or with a vinyl group of their deamination product, thus... 

Fig. 175. Deamination reaction of vinylogous Mannich bases of steroid derivatives.

Among terpenoid substrates bearing the alkyl ketone moiety, 4-caranone" and 2-pincne-4-one," in addition to camphor, are worth mentioning. The stereoselectivity of aminomethylation" is remarkably affected by the reaction conditions moreover, the tendency of 2-pinene-4-one, like steroid substrates, to give the vinylogous Mannich base (Table 8, Chap. I, C. 1) is important. 

In the laboratory of S.F. Martin, a biomimetic approach toward the total synthesis of ( )-strychnine was developed by using tandem vinylogous Mannich addition and HDA reaction to construct the pentacyclic heteroyohimboid core of the natural product.The commercially available 4,9-dihydro-3/-/-P-carboline was first converted to the corresponding A/-acylium ion and then reacted with 1-trimethylsilyloxybutadiene in a vinyiogous Mannich reaction. The resulting cycloaddition precursor readily underwent the expected HDA reaction in 85% yield. 

In the laboratory of S.F. Martin, the vinylogous Mannich reaction (VMR) of a 2-silyloxyfuran with a regioselectively generated iminium ion was utilized as the key step in the enantioselective construction of (+)-croomine. " The carboxylic acid moiety of the starting material was converted to the acid chloride which spontaneously underwent decarbonylation to give the corresponding iminium ion. Reaction of this iminium ion with the 2-silyloxyfuran afforded the desired threo butenolide isomer as the major product. 

Vinylogous Mannich reaction with participation of N- and (9-heterocycles in alkaloid syntheses 02ACR895. 

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