Homoallylamines synthesis

Piperidines. Grieco et al. have described a general synthesis of piperidines by reaction of the acid salt of a primary amine with an allylsilane and 2 equiv. of formaldehyde in water. The reaction involves reaction of iminium ion (a), derived from the amine and formaldehyde, with the allylsilane to form a homoallylamine (b), which can form a second iminium ion (c), which cyclizes with capture of water to the piperidine. 

Another general synthesis of homoallylamines is the conversion of the trifluoroacetate of a primary or secondary amine into the corresponding inunonium salt by the action of aqueous formaldehyde, followed by successive treatment with allyltributylstannane and dilute hydrochloric acid e.g. equations 69 and 70 (TFA = CF3 CO2)195. 

Enantiomerically pure homoallylic amines are very important chiral building blocks for the synthesis of natural products. However, enantioselective methods for homoallylamine are quite undeveloped. In 1995, Itsuno and co-workers reported the first example of enantioselective allylation of an imine (Scheme 7) [13]. The reaction of N-trimethylsilylbenzaldimine 19 with a chiral allylboron reagent 20 in ether at -78 °C afforded the corresponding homoallylamine 22 in 73% ee. 

In this chapter, recent applications of (W)-phcnylglycine amide (1) in asymmetric synthesis are presented (Figure 25.2). The first section deals with diastereoselective Strecker reactions for the preparation of a-amino acids and derivatives, whereas the second section focuses on diastereoselective allylation of imines for preparation of enantiomerically pure homoallylamines. This latter class of compounds is a well-known intermediate for the synthesis of, for example, many types of amines, amino alcohols, and P-amino acids. The final section describes reduction of imines providing enantiomerically pure amines. (S)-3,3-Dimethyl-2-butylamine and (S)-l-aminoindane will be presented as leading examples. The results described in this chapter originate from a longstanding cooperation in the field of chiral technology development between DSM Pharma Chemicals and Syncom B.V. 

Carbohydrate-derived homoallylamines have been demonstrated as being useful chiral synthons for the stereoselective synthesis of P-amino acids. With allyltribu-tylstannane or allyltrimethylsilane as the nucleophiles, glycosyl imines form homoallylamines with high efficiency [29-31]. Promoted by SnCl4, the nucleophile al-lyltributylstannane attacks from the stoically less hindered side. 

Allyltriorganosilanes react with activated C-N double bonds such as iminium salts and Lewis acid-coordinated imines at the y-position to give homoallylamines.14,118 For example, in the presence of BF3, iV-acylimines generated in situ by the reaction of aldehydes or acetals with carbamates are efficiently allylated with allyltrimethylsilanes (Equation (26)).119,119a,12° The use of homochiral crotylsilanes such as 20 leads to highly diastereo- and enantioselective synthesis of homoallylamines (Equation (27)). a Allenylation of the iV-acylimines can be performed with propargylsi lanes. 

Efficient rontes to Q -trifluoromethylated nitrogen heterocycles of various sizes for applications in synthesis of CF3 tagged bioactive molecules were achieved in two steps from Q -(trifluoromethyl)homoallylamines via ene-ene or ene-yne metathesis catalyzed by (2a) and with better conversions by (4a) (equation 4)3 ... 

The asymmetric synthesis of indolizidine alkaloids is described utilizing a palladium-catalyzed amination process. Ionization of an allylic carbonate provides a symmetrical rr-allyl palladium complex, subsequent reaction with a protected homoallylamine gave the product in 93% yield and >99.5% ee (eq 5). ... 

Laschat, S, Kunz, H, Carbohydrates as chiral templates diastereoselective synthesis of A-glycosyl-A-homoallylamines and p-amino acids from imines, J. Org. Chem., 56, 5883-5889, 1991. 

Deloisy, S, Kunz, H, A novel synthesis of chain-extended amino sugar derivatives through Aza-Cope rearrangement of A-galactosyl-A-homoallylamines, Tetrahedron Lett., 39, 791-794, 1998. 

The BF3-promoted reaction of aldehydes or acetals, methyl carbamate, and homochiral crotylsilanes is valuable for highly diastereo- and enantioselective synthesis of homoallylamines (Scheme 10.147) [419]. Interestingly, reaction using aromatic aldehydes or their acetals at low temperature forms stereo-controlled functionahzed pyrrolidines predominantly by a formal [3-1-2] cycloaddition (Section 10.3.3.1). 

Synthesis of homoallylamines by catalytic asymmetric allylation of imines with allyl silanes using a chiral bis x-allyl palladium complex, also using allylstannanes (see 1st edition). 

Homoallylamines. A synthesis of homoallylamines from nitriles consists of consecutive treatment with diisobutylaluminum hydride and triallylamine. Lactams undergo deoxygenative diallylation. ... 

Next, we investigated the synthesis of cermizine D (90) from homoallylamine 105. According to the synthesis of cemuine (86) described above, 105 was acylated with acryloyl chloride to give acrylamide 110. RCM with first-generation Gmbbs catalyst and subsequent hydrogenation afforded bisamide 111. Reduction of bisa-mide 111 with LiAlFLj in THF completed the synthesis of cermizine D (90). 

Billet, M. Preparation of Homoallylamines via a Three-Component Reaction Application to the Synthesis of Nitrogenated Heterocycles. Doctorate Thesis, Strasbourg Univrasity Fiance, 2001, July 2001. 

J. Org. Chem. 2(X)4, 69,4(X)5—4(X)6. Iodine as a very powerful catalyst for three-component synthesis of protected homoal-lylic amines, (c) J.-R. Ella-Menye, W. Dobbs, M. BUlet, P. Klotz, A. Mann, Tetrahedron Lett. 2005, 46, 1897-19(X). Unexpected 1,2 syn diastereoselectivity in the three-component aza Sakurai-Hosomi reaction, (d) M. Sugiura, K. Hirano, S. Kobayashi, J. Am. Chem. Soc. 2004, 126, 7182-7183. a-Aminoallylation of aldehydes with ammonia stereoselective synthesis of homoallylic primary amines, (e) M. BiUet, P Klotz, A. Mann, Tetrahedron Lett. 2(X)1,42, 631-634. Syn diastereoselectivity in the synthesis of homoallylamine using crotylsilane in the three-component reaction, (f) L. Niimi,... 

Another short synthesis of ( )-9a-ep(-quinolizidine 195C (rat-2318), by Mann and coworkers, is worth mentioning in view of its use of a Hnear hydroformylation of a homoallylamine (cyclohydrocarbonylation) to constmct the piperidine ring (Scheme 296). ° A three-component aza-Hosomi—Sakurai reaction between allyltrimethylsilane, butanal, and O-benzylurethane catalyzed by boron trifluoride was used to form the protected homoallylamine ( )-2319. The cyclohydrocarbonylation was then performed with a biphephos/rhodium(I) catalytic system in methanol, yielding the piperidine-containing hemiaminal 2320 in 84% yield. This... 

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