No abstract

The β-azido functionalization reaction provides a mechanistically different enone synthesis that involves treatment of 2 with fluoride anion to effect desilylation and concomitant β-elimination to give 3. Table 1 lists a number of examples of the direct conversion of a TIPS enol ether into the corresponding R,β-enone via a β-azido TIPS enol ether. The β-azido group can be ionized with Me 3 Al or Me 2 AlCl and the intermediate enonium ion trapped by a variety of nucleophiles such as an allylstannane, electron-rich aromatics, TMS enol ethers, Et 2 AlCN, Me 2 AlCCR, Me 4 AlLi, and vinylaluminum reagents to give the products listed in Table 2. The diastereoselectivity of the reaction of a 4-substituted enonium ion with indole shows an unusual increase of selectivity with increasing temperature. Reduction of the azide 2 provides access to β-amino TIPS enol ethers 5, which, for example, can be converted into a cinnamide derivative and cyclized via a putative "ene" process into a γ-lactam.

A new synthesis of wurtzitane (13) is described starting from 2‐oxo‐protoadamant‐4‐ene (2). The key intermediate ketone 7 was obtained by regiospecific ring expansion of the β‐amino alcohol 6. Entry to the wurtzitane system involved solvolysis of the tricyclic unsaturated mesylate 10 (→11).

The &azido functionalization reaction allows ready access to 8-amino triisopropylsilyl (TIPS) enol ethers by reduction of the azidogroup in 2 with lithium aluminum hydride togive 3, Scheme I.' Compound 3 is relatively stable and can be stored as its hydrochloride salt without noticeable decomposition to cyclohexenone.2It was decided toexamine the intramolecularconjugate addition reaction depicted in Scheme 1.3 The cyclization of the acrylamide 4, to give the octahydroquinoline 5, is a favored process (6-endotrig),4 but requires the higher energy cis-amide conformer 4a in order to arrive at 5.5The amine 3 was converted into the cu,&unsaturated amide derivatives 4,8-10,15, and 18 either by direct acylation with an acid chloride in the presence of triethylamine or by mixed anhydride methodology. In all of the examples the yields are high (77-96%), and the amides are stable crystalline compounds that show no tendency to decompose by 8-elimination to cyclohexenone and the corresponding primary amide.Treatment of the amide 4 with Me3AI (3 equiv of 2.0 M solution in toluene) in 1,2-dichloroethane (DCE, at 80 "C) for 42 h produced compound 5 (9%) as a minor component. To our surprise the major product has the structure 7 (43%, structure by X-ray crystallography), Scheme IL6In an effort to improve the yield of 5, a series of experiments were run at different temperatures. It was found that treatment of 4 with Me3AI (2.5 equiv) in 1,2-dichlorobenzene (DCB, at 180 "C) gave the lactam 5 (10%). The major product was shown to have the structure 6 (42%. structure by X-ray crystallography). No reaction occurred if 4 was heated in the absence of Me3AI. Treatment of 8 with Me3AI (2.5 equiv)/l80 "C/DCB for 22 h gaveonlyonecyclization product, 11 (73%). When 9 was treated with MejAI (1.1 equiv in DCB) at 120 "C for 22 h, the lactam 12 (structure by X-ray crystallography) was obtained as a single product in 74%yield. At lower temperatures (83 "C/DCEreflux), the y-lactam 12 (46%) was formed along with the cyclobutane (1) Magnus, P.; Lacour, J. J. Am. Chem. Soc. 1992,114,767. Magnus, P.; Lacour, J. J. Am. Chem. Soc. 1992, 114, 3993. Magnus, P.; Evans, A.; Lacour, J. Terrahedron Leu. 1992, 33, 2933.(2) Other reducing agents can be used to convert 2 into 3 such as 4.4'di-rerr-butylbiphenyl/Li in TH F or Na/NH3.

A synthesis and the determination of the absolute configuration of (−)‐(1S, 3R′ 6R, 8R)‐2, 7‐dioxa‐isotwistane (13) and (−)‐(1R, 3R, 6R, 8R)‐2, 7‐dioxa‐twistane (14) is described. The results for 14 are compared with those for carboeyclic (+)‐twistane (2) of known chirality.