Chair-like transition states

Following the general rules (Section 1.3.3.1.2.), the racemic ( )-2-butenyl derivative 1 exhibits good anti diastereoselectivity on reaction with benzaldehyde2. This is explained as passing through a six-membered chair-like transition state. 

Transmetalation of lithium enolate 1 a (M = Li ) by treatment with tin(II) chloride at — 42 °C generates the tin enolate that reacts with prostereogenic aldehydes at — 78 °C to preferentially produce the opposite aldol diastereomer 3. Diastereoselectivities of this process may be as high as 97 3. This reaction appears to require less exacting conditions since similar results are obtained if one or two equivalents of tin(ll) chloride arc used. The somewhat less reactive tin enolate requires a temperature of —42 C for the reaction to proceed at an acceptable rate. The steric requirements of the tin chloride counterion are probably less than those of the diethyla-luminum ion (vide supra), which has led to the suggestion26 44 that the chair-like transition state I is preferentially adopted26 44. This is consistent with the observed diastereoselective production of aldol product 3, which is of opposite configuration at the / -carbon to the major product obtained from aluminum enolates. 

In contrast to ordinary chiral aldehydes (having no ability to be chelated), the reaction of 9-allyl-9-borabicyclo[3.3.1]nonane(allyl-9-BBN) with the corresponding chiral imines 4 produces the isomer syn-6 either exclusively or predominantly (Cram selectivity Table 8)5,6. The very high 1,2-asymmetric induction is explained by a six-membered. chair-like transition state, in which the inline R group occupies an axial position due to the stereoelectronic effect of imines (R CH = NR). 

Thus, cyclization of the (Z)-hexenyllactam 3b in formic acid leads to quantitative formation of the equatorial formate (27 )-4b, via a chair-like transition state, with conservation of the... 

The smooth cyclizations of ( )- and (Z)-/V-( 3-alkenyl/ethoxy lac tarns with formation of a six-membered ring (via a chair-like transition state) occur completely stereoselectively in quantitative yield with retention of the geometry of the double bond913. 

Formation of the six-membered ring on cyclization of the ( )- and (Z)-4-nonenylhydroxylac-tams [E)-4 and (Z)-4 in formic acid, occurs completely stereoselectivcly to afford the 6.6-spiro compounds (7R )-5 and (7S )-5, respectively51,52. The reaction supposedly proceeds via a chair-like transition state, as depicted. Depending on the reaction conditions, however, 0.5 % 2 or about 25%51 of the five-membered ring isomers are also formed. 

Cyclizations of A-acyliminium ions containing a 3-alkenyl substituent tethered to nitrogen usually proceed with preferential formation of a six-mentbered ring via a chair-like transition state, if the alkene does not have an electronic bias. 

The stereochemical outcome of these reactions has been rationalized as arising from a "tram-de-calyl -like or trans-fused chair-chair -like transition state. The extension of these reactions to acyclic enones has not been successful and only y-1,2-addition products are formed153. 

Cyclization of an organolithium tethered to a suitably positioned carbon-carbon jt-bond is a thermodynamically favorable process that proceeds in a totally regioselective exo-fashion with a high degree of stereocontrol via a transition state in which the lithium atom is intramolecularly coordinated with the remote rc-bond.9 The stereochemical outcome of the cyclization of a substituted 5-hexenyllithium follows from the preference of the substituent to occupy a pseudoequatorial position in the chair-like transition state depicted below.7... 

Mechanistically, a-methylenecyclopentenone (2-391) reacts with ester enolate 2-392 in a Michael addition to give the enolate 2-393, which is then trapped with an aldehyde 2-394 generating the alcoholate 2-396. This eventually cyclizes through lactonization to afford 2-397 in good yield. The products 2-397 are obtained as single diastereomer thus, it can be assumed that the aldol reaction proceeds via the six-membered chair-like transition state 2-395. 

Phenylthio)nitroalkenes are also excellent intermediates for the synthesis of other heterocyclic ring systems. For example, tetrahydropyran carboxylic acid derivatives are formed by the intramolecular addition of oxygen nucleophile to l-(phenylthio)nitroalkene predominantly as the m-isomer (9.1 1) (see Eq. 4.40). The reaction may proceed via the chair-like transition state with two pseudo-equatorial substituents.50... 

Imine 214 (R = H) gave a 3 1 mixture of ot/(3 chloro epimers of 215 (R = H) when a mixture of Lewis acids, TiCl4, and Ti(OiPr)4 was used. The stereoselectivity of the formation of 215 is rationalized by a chair-like transition state 217 with equatorial attack of chloride ion <1998TL7239, 2000JOC655>. 

Z)-enolate of 58 would adopt a closed chair-like transition state that favored exposure of one face of the ketone by 1.5 kcal/mol, leading to the vyn-aldol product corresponding to hypocrellin A (Scheme 7.15). 

In addition to the [4+2] cycloaddition, intramolecular [2+2] photocycloaddition was also successfully used as a main procedure in the synthesis of (i)-ginkgolide B <00JA8453>. The studies on the model reactions and molecular mechanics calculation show that the stereochemistry of the substituents at C6 and C8 should influence severely the reaction diastereoselectivity. When syn-diastereomer 41 is subjected to irradiation the reaction gives a single diastereomer 42 in a quantitative yield since two substituents at C6 and C8 would be in pseudo-equatorial orientation in the chair-like transition state. 

The alkoxycarbonylation reaction is also feasible with 6-exo-nng closure for the preparation of stereodefined THP rings. Using this process, the integral THP moieties of frenolicin B,428 leucascandrolide A,429 and phorboxazole A (Equation (119))430 431 have been prepared. All of these reactions occur with 2,6-m-selectivity, a rationale for which has been advanced by an analysis of chair-like transition states.431... 

Studies show that the Zr-bearing bulky ligand is exclusively located in the bottom hemisphere with respect to the plane of the (Z)-enolate. The aldehyde molecule coordinates with the Zr atom and approaches from the same side, adopting a chair-like transition state. This leads to the formation of erythro-aldols (Scheme 3-9 and 23). For lithium enolate, the attack of alkyl or acyl halides in alkylation or acylation occurs directly on the top face of the enolate. 

The two chair-like transition states 48 and 49 have been suggested to explain the stereochemistry in the reaction. Here structure 48, leading to (S )-carbinol, is favored over the diastereomeric 49, which gives the (R)-enantiomer, because the latter structure with axial-R and equatorial-R group is destablized by the n-n... 

New chiral oxazaborolidines that have been prepared from both enantiomers of optically active inexpensive a-pinene have also given quite good results in the asymmetric borane reduction of prochiral ketones.92 Borane and aromatic ketone coordinate to this structurally rigid oxazaborolidine (+)- or (—)-94, forming a six-membered cyclic chair-like transition state (Scheme 6-41). Following the mechanism shown in Scheme 6-37, intramolecular hydride transfer occurs to yield the product with high enantioselectivity. With aliphatic ketones, poor ee is normally obtained (see Table 6-9). 

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