Mannich reactions vinylogous

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...

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. 

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. 

In particular, Martin and Bur have exploited the vinylogous Mannich reaction extensively as key step in the total synthesis of alkaloids and other nitrogen hetero cycles such as ( jtetrahydroalstonine (6), geissoschizine (7), and akuammicine (8) (Scheme 5.3) [4]. 

Scheme 5.3 Use ofthe vinylogous Mannich reaction as a key step in the total synthesis of alkaloids by the Martin group [4],...

In this review we will attempt to highlight the most important contributions toward the realization of a catalytic, enantioselective, vinylogous Mannich reaction and show the current state of the art. This chapter is organized in such a way that vinylogous Mannich reactions of preformed silyl dienolates in Mukaiyama type reactions will be discussed first followed by direct vinylogous Mannich reactions of unmodified substrates. 

Scheme 5.4 TiCfi catalyzed vinylogous Mannich reaction of vinylketene 0,0 acetals 10 according to Ojima and Brandstadter [5],...

Scheme 5.5 Ti(IV) BINOLate catalyzed vinylogous Mannich reaction according to Martin and Lopez [6],...

Table 5.1 Silver catalyzed vinylogous Mannich reaction of 2 silyloxy furan 17a with aromatic imines according to Hoveyda, Snapper and coworkers [7].

Scheme 5.6 Proposed transition states for the vinylogous Mannich reaction as origin for the enantio and diastereoselectivity [7],...

The vinylogous Mannich reaction of 2 silyloxy furans and imines may also be catalyzed through chiral Brpnsted acids, as shown by Akiyama et al. [10]. Previously, Akiyama [11] and Terada [12] had independently discovered that 3,3 substituted BINOL based phosphoric acids were excellent Bronsted acids for a broad range of mainly imine addition reactions via protonation of the imines and in situ formation of chiral iminium contact ion pairs. Using the slightly modified phosphoric acid 28 as catalyst carrying additional iodine substituents in the 6,6 positions, the y amino substituted butenolides 27 were obtained in excellent enantioselectivity and variable diastereoselectivity (Table 5.4). 

In 2008 our group reported the first example of a catalytic, enantioselective, vinylogous Mannich reaction of acyclic silyl dienolate 30 with imines (Table 5.5) [14]. 

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