Synthesis of homoallylic chiral tertiary alcohols via chelation-controlled diastereoselective nucleophilic addition on alpha-alkoxyketones: application for the synthesis of the C(1)-C(11) subunit of 8-epi-fostriecin.

[reaction: see text] Chiral beta-syn-alkoxyhomoallylic alcohols derived from alkoxyallylboration of aldehydes upon oxidation provided the corresponding chiral ketones. Chelation-controlled nucleophilic addition to these ketones occurred in a highly stereoselective manner to afford anti-homoallylic tertiary alcohols. This methodology has been applied for the synthesis of the C(1)-C(11) subunit of C(8)-epi-fostriecin.

Selective reductions. 59. Effective intramolecular asymmetric reductions of alpha-, beta-, and gamma-keto acids with diisopinocampheylborane and intermolecular asymmetric reductions of the corresponding esters with B-chlorodiisopinocampheylborane.

A comparison of the stereochemistry of the products obtained from the intramolecular asymmetric reduction of a series of keto acids with (-)-diisopinocampheylborane and intermolecular asymmetric reduction of the corresponding series of keto esters with (-)-B-chlorodiisopinocampheylborane ((-)-DIP-Chloride) has been made. The stereochemistry of the hydroxy acids from the reduction of keto acids is dependent only on the enantiomer of the reagent used. The stereochemistry of the products from the reduction of keto esters is also consistent, except those of aliphatic alpha-keto esters. alpha-, beta-, and gamma-keto acids provide the corresponding hydroxy acids in 77-98% ee, and the alpha- and gamma- keto esters afford the hydroxy esters in 82->or=99% ee. beta-Keto esters do not undergo reduction. Although the reduction of delta-keto acids does not proceed under the same reaction conditions, the reduction of delta-keto esters is facile. All of the products from the reduction of gamma-keto acids and esters and delta-keto esters were converted to the corresponding lactones. This study revealed that DIP-Chloride is an efficient reagent for the reduction of alpha-keto esters at low temperatures.

Chiral Synthesis via Organoboranes. 46. An Efficient Preparation of Chiral Pyridino- and Thiopheno-18-crown-6 Ligands from Enantiomerically Pure C(2)-Symmetric Pyridine- and Thiophenediols(1).

Asymmetric reduction of 2,6-diacylpyridines with B-chlorodiisopinocampheylborane provides the corresponding C(2)-symmetric diols in very high de and ee. Asymmetric allylboration of 2,6-pyridinedicarboxaldehyde and 2,5-thiophenedicarboxaldehyde provides the corresponding bis-homoallylic alcohols in very high de and ee. These optically pure diols were converted to the disodium or dipotassium salts and treated with tetra(ethylene glycol) ditosylate to obtain the corresponding chiral pyridino and thiopheno-18-crown-6 ligands. However, the perfluoroalkyl diols failed to provide the macrocycles.

The Critical Importance of Water in the Asymmetric Allylboration of N-Trimethylsilylbenzaldimines with B-Allyldiisopinocampheylborane.

The free aldimine is probably the intermediate in the asymmetric allylboration of N-trimethylsilylaldimines in the presence of water (see scheme), which is critical for the reaction. The aldimine is rapidly captured by the allylborating agent. Ipc2 BAll=B-allyldiisopinocampheylborane.

Markovnikov Hydroboration of Perfluoroalkylethylenes.

A Markovnikov regioselectivity of 92 % or higher is achieved in the hydroboration of a series of perfluoroalkylethylenes and 2',3',4',5',6'-pentafluorostyrene with dichloro- and dibromoborane to provide the corresponding (fluoroalkyl)dihaloboranes (see reaction).

Chiral Synthesis via Organoboranes. 47. Efficient Synthesis of Unsymmetrical Ketones and Enantiomerically Pure Spiroketals Using (+/-)-Isopinocampheyldichloroborane.

Readily prepared and stable (+/-)-isopinocampheyldichloroborane [(+/-)-IpcBCl(2)] was conveniently used for the stepwise hydroboration of two different alkenes using the in situ reduction-hydroboration protocol to give mixed trialkylboranes, IpcBR(1)R(2). Convenient elimination of alpha-pinene from these trialkylboranes by treatment with an aldehyde, RCHO, provided the borinate ester, R(1)R(2)BOCH(2)R. This intermediate was readily converted into the unsymmetrical ketones, R(1)COR(2), in high yields and purity, by an established method. This methodology was successfully applied to the synthesis of enantiomerically pure spiroketals using optically pure TBS ether protected homoallylic alcohols as the alkenes for stepwise hydroboration.