Enantioselective C–C Bond Formation as a Result of the Oriented Prochirality of an Achiral Aldehyde at the Single-Crystal Face upon Treatment with a Dialkyl Zinc Vapor**

The origin of biological homochirality, such as that seen in l amino acids and d sugars, is one of the most important subjects for broad research. Circularly polarized light, chiral inorganic crystals, such as quartz, chiral organic crystals, and spontaneous absolute asymmetric synthesis have been proposed as candidates for the origin of chirality. Supramolecular arrangement by an external chiral factor has also been suggested. The induced chirality should be enhanced to high enantiomeric enrichment by suitable multiplication and amplification mechanisms, such as amino acid catalyzed aldol reactions and asymmetric autocatalysis. Lahav, Holland and Richardson originally suggested the concept of a reaction at the enantiotopic face of an achiral single crystal and later reported oxidation reactions of olefinic compounds. Because the reagents reacted directly with the oriented molecules in the crystal, the products formed in a stereospecific manner to provide optically active compounds corresponding to the prochirality of the substrate at the crystal surface. Since chiral compounds can be obtained from achiral compounds, enantioselective reactions on a selected face have been considered as another possible origin of chirality. Recently, Kuhn and Fischer reported a reduction at the enantiotopic surface of a ketone to provide a chiral alcohol with up to 26% ee. Some chiral effects at enantiotopic surfaces have been reported, such as molecular recognition, crystallization, and dehydration. Thus, enantioselective C C bond formation at specific enantiotopic surfaces is a challenge. We herein report the enantioselective addition of diisopropylzinc (iPr2Zn) at a particular single-crystal face of aldehyde 1 to form a chiral secondary alcohol 2 (Scheme 1).When a single-crystal surface was treated with iPr2Zn vapor, the enantioselective isopropylation proceeded to afford the chiral 5-pyrimidyl alkanol 2 with the absolute configuration corresponding to the oriented prochirality of the achiral aldehyde 1. We previously reported that 2-(alkylethynyl)and 2(trialkylsilylethynyl)pyrimidine-5-carbaldehyde serve as excellent substrates in asymmetric autocatalysis with the amplification of enantiomeric excess. Thus, as an achiral substrate, we selected 2-(tert-butyldimethylsilylethynyl)pyrimidine-5-carbaldehyde (1), which can be prepared from 5bromo-2-iodopyrimidine by a coupling reaction with tertbutyldimethylsilylacetylene and formylation (see the Supporting Information). A single crystal of 1 with well-defined crystal faces could be obtained by recrystallization from a solvent mixture of cumene and ethyl acetate by slow evaporation (Figure 1a). Single-crystal X-ray structure analScheme 1. Enantioselective addition of diisopropylzinc to the pyrimidine-5-carbaldehyde 1 to form the 5-pyrimidyl alkanol 2.