Morita intramolecular

Roush and coworkers developed a new one-pot sequence consisting of an intramolecular Diels-Alder- and an intramolecular vinylogous Morita-Baylis-Hillman-cyclization for the synthesis of spinosyns [31]. These compounds are poly-ketide natural products possessing extraordinary insecticidal activity. 

Intramolecular versions of the Morita-Baylis-Hillman reaction have also met with success using a dual Lewis acid/Lewis base catalyst system. Miller has shown that a combination of A-methyl imidazole (132) (10 mol%) and... 

An interesting alternative intramolecular cyclisation was discovered by Jprgensen and co-workers [187]. Although not strictly exploiting an enamine intermediate, the transformation represents a secondary amine catalysed Morita-Baylis-Hillman reaction leading to a series of highly functionalised cyclohexene products. Reaction of the Nazarov reagent 137 with a,P-unsaturated aldehydes in the presence of the diarylprolinol ether 30 led to the cyclohexene products 138 (49-68% yield 86-96% ee) via a tandem Michael/Morita-Baylis-Hillman reaction (Scheme 54). 

A study of the effect of the Michael acceptor configuration on the efficiency of intramolecular Morita-Baylis-Hillman reactions has been performed. Enones containing a pendant aldehyde moiety attached at the -position of the alkene group were employed as substrates and the reactions were catalysed by a phosphine. In all cases examined, with Ph3P as the catalyst, cyclization of (Z)-alkene (117) gave 2.5-8.5 times higher yield than with the E-isomer (115) under identical reaction conditions, both affording the same product (116). Steric effects are believed to be the source of this difference in reactivity.172... 

Intramolecular hydrogen bonding has been proposed to facilitate nucleophilic addition of sulfones to the Morita-Baylis-Hillman adducts in a single step to produce the substituted allyl sulfones.178... 

An intramolecular vinylogous Morita-Baylis-Hillman reaction, followed by intramolecular aldol cyclization,129 is described under Intramolecular Aldols above. 

A highly enantioselective proline-catalysed intramolecular Morita-Baylis-Hillman reaction of hept-2-enedial (111) has been reported. Addition of imidazole to the mixture resulted in an unusual inversion of enantioselectivity.149 The first example of a TiCU-mediated Morita-Baylis-Hillman-type reaction of cy-acetyl cyclic ketene dithioacetals with arylaldehydes has been described.150... 

Furthermore, following an analogous methodology, combining the Morita-Baylis-Hillman reaction and the Trost-Tsuji reaction, Krische and co-workers have obtained allyl-substituted cyclopentenones 94 [84], Reaction was initiated by Michael addition of tributyl phosphine to an enone moiety 92, generating a latent enolate 93 which reacts intramolecularly with a jr-allylPd complex as the electrophile partner. A final -elimination step of trib-utylphosphine, favored by the presence of the methoxide ion, delivered the substituted cyclopentenones 94 (Scheme 36). 

A new route to 6-substituted pyrrolo[2,l-b]thiazoles 58 takes advantage of an intramolecular thermal cyclization of acetates 56 <07S3037>. These acetates are easily derived from the Morita-Baylis-Hillman adducts of thiazole-2-carboxaldehyde. This strategy has also been extended to the synthesis of the tricyclic analogs 60. 

S. Minato, T. Osa, M. Morita, A. Nakamura, H. Ikeda, F. Toda, A. Ueno, Intramolecular Excimer Formation and Molecular Recognition of Modified Cyclodextrins Appended by Two Naphthalene Rings , Photochem. PhotobioL, 54,593 (1991)... 

Mergott, D. J., Frank, S. A., Roush, W. R. Application of the Intramolecular Vinylogous Morita-Baylis-Hillman Reaction toward the Synthesis of the Spinosyn ATricyclic Nucleus. Org. Lett. 2002, 4, 3157-3160. 

Chen and coworkers published a formal [3 + 3]-type reaction to give highly substituted cyclohexenes 8. This domino process consists of an allylic-allylic alkylation of an a,a-dicyanoalkene derived from 1-indanone and Morita-Baylis-Hillman carbonates, following an intramolecular Michael addition, by employing dual orga-nocatalysis of commercially available modified cinchona alkaloid (DHQD)2AQN If (hydroquinidine (anthraquinone-l,4-diyl) diether) and (S)-BINOL. The cyclic adducts... 

Mergott, D.J., Frank, S.A., and Roush, W.R., Application of the intramolecular vinylogous Morita-Baylis-Hillman reaction toward the synthesis of the spinosyn A tricyclic nucleus, Org. Lett., 4, 3157, 2002. 

There have been only a few reports on asymmetric versions of the intramolecular MBH reaction Scheme 1.105 shows one representative example. The intramolecular Morita Baylis Hillman reaction has been achieved with unprecedented levels of enantioselectivity by using a co-catalyst system involving pipecolinic acid and iV-methylimidazole cyclic MBH products 289 were... 

Acetates of Morita-Baylis-Hillman (MBH) adduct 2 can be stereoselectively prepared by the reaction of acetyl chloride in the presence of a base or, alternatively, acetic anhydride in cone. H2S04. However, acetates 2 derived from aromatic aldehydes (R = Ar) prefer to undergo isomerization to generate the thermodynamically more stable acetate 3, either by intramolecular rearrangement... 

The reaction course of the intramolecular cycloalkylation of precursors (139) is highly dependent on the nature of the nucleophiUc catalyst used (as depicted in Scheme 18). A DFT investigation of this Morita-BayUs-Hillman-Uke ring-closing processes has now been performed to rationalize the experimental results observed. " The differences and the similarities among the reactions of (139) with PMc3 and NHC have been discussed in detail. 

Morita Y, Maid S, Fukui K, Ohba T, Kawai J, Sato K, Shiomi D, Takui T, Nakasuji K (2001) New stable neutral radical with intramolecular hydrogen bonding synthesis and characterization of 2,5,8-tri-tert-butyl-7-hydroxy-6-oxophenalenoxyl. Org Lett 3 3099-3102... 

The L-threonine-derived phosphine-sulfonamide (23) is one of the best catalysts for the enantioselective aza-Morita-Baylis-Hillman reaction. A DPT study has identified ( ) a key intramolecular N-H—O hydrogen-bonding interaction between the sulfonamide... 

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