Cyclopentane-forming annulations

The 4,5-threo-thiobutenolide 91 thus obtained was then reduced and shortened by one carbon atom to arrive at aldehyde 92 onto which a highly stereoselective cyclopentane-forming annulation was performed via a TBSOTf/DIPEA-promoted silylative protocol. In the event, a major 2,3-cA-configured bicycle educt 94 was isolated in a 82% yield, accompanied by only 7% of fram-isomer 93. Completion of the synthesis entailed the reductive cleavage of the thiolactone bond within 93 and 94, followed by acidic deprotection, giving l-deoxy-l-thio-4a-carba-[ -D-... 

Scheme 14.29 Stereodivergency of chiral imidazolium- and triazolium-promoted cyclopentane-forming annulations.

The product in entry 1 of Scheme 2.10 is commonly known as the Wieland-Miescher ketone and is a useful starting material for the preparation of steroids and terpenes. The Robinson annulation to prepare this ketone can be carried out enantioselectively by using the amino acid L-proline to form an enamine intermediate. The 5-enantiomer of the product is obtained in high enantiomeric excess.89 This compound and the corresponding product obtained from cyclopentane-1,3-dione90 are key intermediates in the enantiose-lective synthesis of steroids.91... 

The reaction pathway may be supported by the observations with 4,4-dimethyl-5-trimethylsilyloxyhept-l-en-6-yne and its positional isomer 4,4-dimethyl-3-trimethylsilyloxyhept-l-en-6-yne. These react with Me2PhSiH to give the corresponding aldehydes, 280 and 282, respectively, as a mixture of two diastereomers under the conditions similar to mode 1 in Scheme 13 (Equations (47) and (48)). In the reaction of 281, an appreciable amount of 283 is formed concomitantly, which implies that the trimethylsilyloxy group at an allylic position likely retards the cyclopentane annulation step. 

As expected, addition of propenyl lithium to ketoacetal 33 occurs preferentially (diastereoselectively = 8 1) from the face opposite the side chain to provide, after silylation, the rearrangement substrate 34. Treatment of this intermediate with SnCl at -23 C for 5 min occasioned the desired reorganization to afford the cw-hydroazulenone 35, as a 5 1 mixture of methoxy epimers, in excellent yield. That the two products produced from 34 were indeed stereoisomers was apparent from their conversion to the same diketone upon RuO oxidation [25]. The alcohol precursor of 34 cannot directly be employed in this ring-enlarging cyclopentane annulation, since it undergoes facile cyclization to form a bicyclic acetal, an intermediate that is a dead-end with regard to transformation to 35. 

These annulations are governed by conformational factors. In 1968 Johnson predicted that the dominant conformation for C(3),C(4)-dialkyl-substituted cyclohex-enones, such as 5, has the C(4) substituent oriented axially because of A-strain (Eq. 7)P In addition, the diene moiety of S can exist in either a transoid or a cisoid conformation, cf. conformations lii and iv, respectively. In simple acyclic 1,3-dienes, the planar transoid conformation is more stable than the cisoid form. However, examination of a Drieding model of iii suggests that nonbonded steric interactions tween the equatorial C(4) methyl substituent and the C(3) vinyl group would force the dienone into a cisoid conformation. This orientation clearly precludes 1,6-nucleophilic attack by the silicate species thus, 1,4-addition occurs to generate a cyclopentane ring. 

Reactions of 6- and 7-bromo-2-hexenoates with active methylene compounds, mediated by K2CO3, deliver highly substituted cyclopentane derivatives via a sequence of SN2-conjugate addition reactions (formal [4-1-1] annulation) in a diastereoselective manner (Scheme 6.21). Conceivably, the anion formed from the active methylene... 

Addition of an T -allyl-Fp complex to this compound affords an T -aIlyl-Fp-substituted cycloheptatriene system. Two double bonds are involved in an (T -diene)iron complex. The remaining free double bond of the silyl enol ether attacks as a nucleophile at the cationic r -alkene-Fp moiety to form an (Tj -diene)iron complexed cyclopentane annulated cycloheptadienone. Treatment with CAN in methanol under carbon monoxide atmosphere releases the methoxycarbonyl-substituted free ligand (Scheme 4-25). Reaction of the Ti -dienyliumiron intermediate of Scheme 4-25 with an ( , Z)-isomeric mixture of ri -crotyl-Fp proceeds with high diastereoselectivity. Four new stereogenic centers are formed in the course of this formal [3+2] cycloaddition. A hetero [3+2] cycloaddition is also feasible between T -ailyl-Fp complexes and aromatic aldehydes in the presence of zinc chloride or titanium(IV) chloride to provide tetrahydrofuran derivatives (Scheme 4-26). A 1,2-shift of the iron complex fragment occurs in the course of this reaction. Employment of imines affords the corresponding pyrrolidines. ... 

---